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1.
  • Landgren, Sara, 1980, et al. (author)
  • Genetic variation of the ghrelin signaling system in females with severe alcohol dependence
  • 2010
  • In: Alcoholism: Clinical and Experimental Research. - : Wiley. - 0145-6008 .- 1530-0277. ; 34:9, s. 1519-1524
  • Journal article (peer-reviewed)abstract
    • INTRODUCTION: Central ghrelin signaling is required for the rewarding effects of alcohol in mice. Because ghrelin is implied in other addictive behaviors such as eating disorders and smoking, and because there is co-morbidity between these disorders and alcohol dependence, the ghrelin signaling system could be involved in mediating reward in general. Furthermore, in humans, single nucleotide polymorphisms (SNPs) and haplotypes of the pro-ghrelin gene (GHRL) and the ghrelin receptor gene (GHSR) have previously been associated with increased alcohol consumption and increased body weight. Known gender differences in plasma ghrelin levels prompted us to investigate genetic variation of the ghrelin signaling system in females with severe alcohol dependence (n = 113) and in a selected control sample of female low-consumers of alcohol from a large cohort study in southwest Sweden (n = 212). METHODS: Six tag SNPs in the GHRL (rs696217, rs3491141, rs4684677, rs35680, rs42451, and rs26802) and four tag SNPs in the GHSR (rs495225, rs2232165, rs572169, and rs2948694) were genotyped in all individuals. RESULTS: We found that one GHRL haplotype was associated with reports of paternal alcohol dependence as well as with reports of withdrawal symptoms in the female alcohol-dependent group. Associations with 2 GHSR haplotypes and smoking were also shown. One of these haplotypes was also negatively associated with BMI in controls, while another haplotype was associated with having the early-onset, more heredity-driven, type 2 form of alcohol dependence in the patient group. CONCLUSION: Taken together, the genes encoding the ghrelin signaling system cannot be regarded as major susceptibility genes for female alcohol dependence, but is, however, involved in paternal heritability and may affect other reward- and energy-related factors such as smoking and BMI.
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2.
  • Landgren, Sara, 1980, et al. (author)
  • The ghrelin signalling system is involved in the consumption of sweets.
  • 2011
  • In: PLos One. - : Public Library of Science (PLoS). - 1932-6203. ; 6:3
  • Journal article (peer-reviewed)abstract
    • The gastric-derived orexigenic peptide ghrelin affects brain circuits involved in energy balance as well as in reward. Indeed, ghrelin activates an important reward circuit involved in natural- as well as drug-induced reward, the cholinergic-dopaminergic reward link. It has been hypothesized that there is a common reward mechanism for alcohol and sweet substances in both animals and humans. Alcohol dependent individuals have higher craving for sweets than do healthy controls and the hedonic response to sweet taste may, at least in part, depend on genetic factors. Rat selectively bred for high sucrose intake have higher alcohol consumption than non-sucrose preferring rats and vice versa. In the present study a group of alcohol-consuming individuals selected from a population cohort was investigated for genetic variants of the ghrelin signalling system in relation to both their alcohol and sucrose consumption. Moreover, the effects of GHS-R1A antagonism on voluntary sucrose-intake and operant self-administration, as well as saccharin intake were investigated in preclinical studies using rodents. The effects of peripheral grelin administration on sucrose intake were also examined. Here we found associations with the ghrelin gene haplotypes and increased sucrose consumption, and a trend for the same association was seen in the high alcohol consumers. The preclinical data show that a GHS-R1A antagonist reduces the intake and self-administration of sucrose in rats as well as saccharin intake in mice. Further, ghrelin increases the intake of sucrose in rats. Collectively, our data provide a clear indication that the GHS-R1A antagonists reduces and ghrelin increases the intake of rewarding substances and hence, the central ghrelin signalling system provides a novel target for the development of drug strategies to treat addictive behaviours.
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3.
  • Albrektsen, G., et al. (author)
  • Data on gender contrasts in the risk of incident myocardial infarction by age. The Tromso Study 1979-2012
  • 2017
  • In: Data in Brief. - : Elsevier BV. - 2352-3409. ; 13, s. 779-784
  • Journal article (peer-reviewed)abstract
    • The data presented in this article relate to the research article entitled "Risk of incident myocardial infarction by gender: Interactions with serum lipids, blood pressure and smoking. The Tromso Study 1979-2012" (Albrektsen et al., 2017) [1]. Data quantify the gender differences in the risk of myocardial infarction (MI) in terms of incidence rate ratios (IRR), in subgroups defined by serum lipids, blood pressure and smoking among persons aged 35-54 years, 55-74 years and 75-94 years, respectively. Data also describe the age- and gender-specific linear associations with the coronary heart disease (CHD) risk factors. IRRs for combined categories of age, gender and a CHD risk factor, with each category compared to the same reference group, are also shown. IRRs were calculated as estimates of relative risk in Poisson regression analyses of person-years at risk. Among 33,859 individuals at risk, a total of 622,1308 and 816 were diagnosed with Ml at ages 35-54, 55-74 and 75-94 years, respectively. (C) 2017 The Authors. Published by Elsevier Inc.
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4.
  • Albrektsen, G., et al. (author)
  • Lifelong gender gap in risk of incident myocardial infarction: The Tromsø study
  • 2016
  • In: JAMA Internal Medicine. - : American Medical Association (AMA). - 2168-6106. ; 176:11, s. 1673-1679
  • Journal article (peer-reviewed)abstract
    • IMPORTANCE It is not clear to what extent the higher incidence of coronary heart disease (CHD) in men vs women is explained by differences in risk factor levels because few studies have presented adjusted risk estimates for sex. Moreover, the increase in risk of CHD in postmenopausal women, possibly hormone related, may eventually eliminate the sex contrast in risk, but age-specific risk estimates are scarce. OBJECTIVE To quantify the difference in risk of incidentmyocardial infarction (MI) between men and women. DESIGN, SETTING AND PARTICIPANTS Population-based prospective study from Tromsø, Norway, comprising 33 997 individuals (51% women). Median follow-up time during ages 35 to 102 years was 17.6 years. Incidence rates (IRs) and incidence rate ratios (IRRs, relative risk) of MI were calculated in Poisson regression analysis of person-years at risk. The data analysis was performed in November 2015. EXPOSURES Sex, age, birth cohort, serum lipid levels, blood pressure, lifestyle factors, diabetes. MAIN OUTCOMES AND MEASURES Incident MI. RESULTS A total of 2793 individuals (886 women) received a diagnosis of MI during follow-up in the period 1979 through 2012. The IR increased with age in both sexes, with lower rates for women until age 95 years. Adjusted for age and birth cohort, the overall IRR for men vs women was 2.72 (95%CI, 2.50-2.96). Adjustment for high-density lipoprotein cholesterol and total cholesterol levels had the strongest impact on the risk estimate for sex, followed by diastolic blood pressure and smoking. However, the sex difference remained substantial even after adjustment for these factors (IRR, 2.07; 95%CI, 1.89-2.26). Men had higher risk throughout life, but the IRRs decreased with age (3.64 [95%CI, 2.85-4.65], 2.00 [95%CI, 1.76-2.28], and 1.66 [95%CI, 1.42-1.95] for age groups 35-54, 55-74, and 75-94 years, respectively). Adjustment for systolic blood pressure, diabetes, body mass index, and physical activity had no notable impact. CONCLUSIONS AND RELEVANCE The observed sex contrast in risk of MI cannot be explained by differences in established CHD risk factors. The gender gap persisted throughout life but declined with age as a result of a more pronounced flattening of risk level changes in middle-aged men. The minor changes in IRs when moving from premenopausal to postmenopausal age in women make it unlikely that changes in female hormone levels influence the risk of MI.
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5.
  • Albrektsen, G., et al. (author)
  • Risk of incident myocardial infarction by gender: Interactions with serum lipids, blood pressure and smoking. The Tromso Study 1979-2012
  • 2017
  • In: Atherosclerosis. - : Elsevier BV. - 0021-9150. ; 261, s. 52-59
  • Journal article (peer-reviewed)abstract
    • Background and aims: Overall, men have roughly twice the risk of myocardial infarction (MI) compared to women, but what causes this contrast is unclear. Identification of subgroups where the gender contrast in risk is particularly low or high, may provide new insight. In the search for such subgroups, we focus on gender-specific effects of established coronary heart disease (CHD) risk factors. Heterogeneity across age groups is also explored. Methods: Population-based prospective study from Tromso, Norway, comprising 33,859 individuals (51% women); 2746 individuals (854 women) received a diagnosis of MI during follow-up at ages 35-94 years. Incidence rate ratios (IRR) were calculated as estimates of relative risk in Poisson regression analyses. Results: The association between total cholesterol and risk of MI was stronger for men than women, and IRR for men vs. women accordingly increased with increasing cholesterol, but the risk was higher for men in all subgroups (IRR in range 1.63-3.27), except among older people with low cholesterol levels. The adverse effect of increasing blood pressure (BP) was stronger for women, and IRR for gender diminished with increasing systolic (from 3.90 to 1.38) and diastolic BP (from 2.87 to 1.54). The gender contrast in risk was also substantially reduced in smokers >= 75 years. Associations with high-density lipoprotein cholesterol (HDL-C) did not differ between genders. Conclusions: Gender heterogeneity in associations with total cholesterol but not HDL-C indicates gender differences in associations with non-HDL-C. The stronger association with BP in women may relate to more severe hypertension-induced left ventricular hypertrophy. (C) 2017 Elsevier B.V. All rights reserved.
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6.
  • Aminoff, A, et al. (author)
  • Allele-specific regulation of MTTP expression influences the risk of ischemic heart disease.
  • 2010
  • In: Journal of lipid research. - 0022-2275 .- 1539-7262. ; 51:1, s. 103-11
  • Journal article (peer-reviewed)abstract
    • Promoter polymorphisms in microsomal triglyceride transfer protein (MTTP) have been associated with decreased plasma lipids but an increased risk for ischemic heart disease (IHD), indicating that MTTP influences the susceptibility for IHD independent of plasma lipids. The objective of this study was to characterize the functional promoter polymorphism in MTTP predisposing to IHD and its underlying mechanism. Use of pyrosequencing technology revealed that presence of the minor alleles of the promoter polymorphisms -493G>T and -164T>C result in lower transcription of MTTP in vivo in the heart, liver, and macrophages. In vitro experiments indicated that the minor -164C allele mediates the lower gene expression and that C/EBP binds to the polymorphic region in an allele-specific manner. Furthermore, homozygous carriers of the -164C were found to have increased risk for IHD as shown in a case-control study including a total of 544 IHD patients and 544 healthy control subjects. We concluded that carriers of the minor -164C allele have lower expression of MTTP in the heart, mediated at least partly by the transcription factor CCAAT/enhancer binding protein, and that reduced concentration of MTTP in the myocardium may contribute to IHD upon ischemic damage.
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7.
  • Arking, D. E., et al. (author)
  • Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization
  • 2014
  • In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 46:8, s. 826-836
  • Journal article (peer-reviewed)abstract
    • The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼ 8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD. © 2014 Nature America, Inc.
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8.
  • Bengtsson, Inger M., 1944, et al. (author)
  • The cortisol awakening response and the metabolic syndrome in a population-based sample of middle-aged men and women.
  • 2010
  • In: Metabolism. - : Elsevier BV. - 0026-0495 .- 1532-8600. ; 59:7, s. 1012-9
  • Journal article (peer-reviewed)abstract
    • The objective was to explore the relationship between the cortisol awakening response (CAR) and the metabolic syndrome (MetS) as defined by the National Cholesterol Education Program criteria. The final study sample consisted of 91 women (14 with MetS) and 84 men (15 with MetS), aged 45 to 70 years, from a general population sample. The only exclusion criteria were no consent, pregnancy, or insufficient cortisol testing. On the day of measurement (weekday), salivary cortisol was sampled at awakening and 15 minutes after awakening. Relative CAR (CAR%) and the MetS were the main variables studied. Results showed that, in women with the MetS, cortisol at awakening was significantly lower (mean, 8.92 vs 12.33 nmol/L; P = .05) and the CAR was significantly higher (91.4% vs 36.5%, P < .001) than in women without the syndrome. Significant difference in the relative CAR was also present between men and women with MetS (38.5% and 91.4%, respectively; P = .02). No difference was seen in the awakening response comparing men with and without the MetS. In a regression model, the response to awakening was dependent on the MetS in women (F1,89 = 13.19, P < .001); but the model was not significant in men. Furthermore, the awakening response was associated with more depressive symptoms in women (F1,80 = 8.12, P = .01) and with weekday/weekend cortisol sampling in men (F1,82 = 4.63, P = .03). The association between the relative CAR and the MetS remained significant but somewhat attenuated after adjusting for depressive symptoms (P = .01). Results indicate a sex difference in the CAR% in the presence of the MetS independent of depressive symptoms, a known correlate of the MetS.
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10.
  • Berg, Christina, 1963, et al. (author)
  • Decreased exhaled nitric oxide (FENO) in obese with asthma symptoms: Data from the population study INTERGENE/ADONIX
  • 2011
  • In: Chest. - : Elsevier BV. - 0012-3692. ; 139:5, s. 1109-1116
  • Journal article (peer-reviewed)abstract
    • Abstract BACKGROUND: Several studies have demonstrated an association between obesity and asthma. However, it is uncertain if fraction of exhaled nitric oxide (FENO), which is used as a marker of airway inflammation, and atopy are associated with BMI. The aim was to examine if obese with asthma symptoms have a different phenotype of asthma than non-obese as indicated by FENO. METHODS: The subjects (n=2187) consist of women and men, aged 25-74, living in Gothenburg, Sweden, participating in the randomly selected INTERGENE study cohort. Measurements include anthropometric measures, bioelectric impedance, FENO, pulmonary function, blood samples for IgE and questionnaires including items on respiratory symptoms. Obesity was defined as BMI≥30 kg/m(2). In this cross-sectional analysis, general linear models were used to analyse how FENO was associated with anthropometry, body composition, wheezing and atopy. RESULTS: In non-obese subjects, wheezing was associated with raised FENO and atopy, whereas, in contrast, obese with wheezing had lower FENO than obese without wheezing (16.1 v.s. 19.1 ppb, p<0.01). The prevalence of atopy was similar in both those sub-groups (25.0 v.s. 20.7%, p=0.4). Similarly, in 395 subjects (19%) who reported wheezing, FENO was negatively associated with BMI, waist-hip ratio and percentage of body fat, while no significant relationships were observed in those without respiratory symptoms. CONCLUSIONS: Wheezing was significantly associated with reduced FENO in obese subjects, whereas there was a positive association between wheezing and FENO among the non-obese, indicating a possible difference in asthma phenotype, based on body weight.
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11.
  • Berg, Christina, 1963, et al. (author)
  • Eating patterns and portion size associated with obesity in a Swedish population.
  • 2009
  • In: Appetite. - : Elsevier BV. - 1095-8304 .- 0195-6663. ; 52:1, s. 21-6
  • Journal article (peer-reviewed)abstract
    • The objective of this study was to describe the association between meal pattern and obesity. The study is based on data from the INTERGENE research programme, and the study population consists of randomly selected women and men, aged 25-74, living in the V?stra G?taland Region in Sweden. A total of 3610 were examined. Participants with measured BMI>/=30 were compared with others (BMI<30) with respect to questionnaire data on habitual meal patterns and intake of energy estimated from food frequencies and standard portions. Odds ratios (OR) with 95% confidence intervals were adjusted for age, sex, smoking and physical activity in logistic regression models. Being obese was significantly associated with omitting breakfast, OR 1.41 (1.05-1.90), omitting lunch OR 1.31 (1.04-1.66) and eating at night OR 1.62 (1.10-2.39). Obesity was also related to significantly larger self-reported portion sizes of main meals. No statistically significant relationship with intake of total energy was revealed. Thus, the results indicate that examination of meal patterns and portion sizes might tell us more about obesogenic food patterns than traditional nutrient analyses of food frequencies. Being obese was associated with a meal pattern shifted to later in the day and significantly larger self-reported portions of main meals.
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13.
  • Berg, Christina, 1963, et al. (author)
  • Food patterns and cardiovascular disease risk factors: the Swedish INTERGENE research program.
  • 2008
  • In: The American journal of clinical nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 88:2, s. 289-97
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Analyzing the impact of the intake of many foods simultaneously provides additional knowledge about analyses of nutrients and might make it easier to implement recommendations for the public. OBJECTIVE: The objective was to examine food patterns in a Swedish population and determine how they are related to metabolic risk factors for cardiovascular disease. DESIGN: The study is based on data from the INTERGENE population study of women and men aged 25-74 y in western Sweden. Dietary patterns were identified with cluster analysis of 93 food frequencies reported by 3452 participants. Associations with features of the metabolic syndrome, including blood lipids, blood pressure, and anthropometric measures, were analyzed. RESULTS: Five distinct food patterns were identified, of which one was interpreted as a "healthy" reference pattern. This healthy cluster was distinguished by more frequent consumption of high-fiber and low-fat foods and lower consumption of products rich in fat and sugar. The 4 other clusters differed significantly from the reference cluster with respect to prevalence of cardiovascular disease risk factors and the metabolic syndrome. For example, body mass index and waist-to-hip ratio were significantly higher in a cluster characterized by high consumption of energy-dense drinks and white bread and low consumption of fruit and vegetables (P < 0.0001 and P = 0.004, respectively). CONCLUSIONS: It is possible to distinguish food patterns that are related to obesity and obesity-related cardiovascular disease risk factors in contrast with a more healthy pattern conforming with current dietary guidelines. Thus, the results indicate no reason for questioning the current recommendations.
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  • Berg, Christina, 1963, et al. (author)
  • Trends in blood lipid levels, blood pressure, alcohol and smoking habits from 1985 to 2002: results from INTERGENE and GOT-MONICA.
  • 2005
  • In: European journal of cardiovascular prevention and rehabilitation : official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology. - 1741-8267. ; 12:2, s. 115-25
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Favourable trends in cardiovascular disease have been observed in Sweden. The aim of this study was to study secular trends in a variety of cardiovascular risk factors. METHODS: Total-, low-density (LDL) and high-density lipoprotein (HDL) serum cholesterol; serum triglycerides; systolic and diastolic blood pressure; self-reported smoking and alcohol consumption were studied in repeated cross-sectional surveys. Data from four population-based samples in Goteborg, Sweden were used-WHO MONICA project 1985, 1990 and 1995, and INTERGENE 2002. A total of 2931 females and 2691 males aged 25-64 consisting of 1021-1624 randomly selected subjects at each survey period participated. RESULTS: Serum cholesterol levels showed downward trends but the decline in both total- and LDL-cholesterol seems to be levelling off from 1995 and onwards. No significant changes were observed in serum triglyceride, HDL-serum cholesterol or blood pressure levels. The majority of the participants had higher total- and LDL-serum cholesterol levels than currently recommended. Antihypertensive medical treatment increased in women and the oldest men. The prevalence of smoking decreased from 39 to 25% in women and 35 to 20% in men respectively from 1985-2002. In contrast, the prevalence of subjects consuming strong beer and wine, respectively, at least once a week almost doubled from 1990-2002. CONCLUSIONS: Cardiovascular risk factor patterns change continuously and need to be monitored. The favourable trends in LDL-serum cholesterol and smoking in the Goteborg surveys were paralleled by less favourable trends in being overweight and alcohol consumption.
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16.
  • Berg, Christina, 1963, et al. (author)
  • Trends in overweight and obesity from 1985 to 2002 in Göteborg, West Sweden.
  • 2005
  • In: International journal of obesity (2005). - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 29:8, s. 916-24
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: To study secular trends in overweight and selected correlates in men and women in Göteborg, Sweden. DESIGN: Cross-sequential population-based surveys. SUBJECTS: A total of 2931 female and 2691 male subjects aged 25-64 y participated in WHO MONICA surveys (1985, 1990, 1995) and the INTERGENE study (2002). MEASUREMENTS: Body mass index (BMI), waist-to-hip ratio (WHR), prevalence of overweight (BMI> or =25 kg/m(2)), and obesity (BMI> or =30 kg/m(2)). RESULTS: Mean body weight increased by 3.3 kg for women and 5 kg for men, with a significant upward trend for BMI in men but not women over the 17-y observation period. The prevalence of overweight and obesity increased significantly in both sexes over the period. The largest increase was observed in men, and in women aged 25-34 y. In 2002, the prevalence of overweight was 38% in women and 58% in men, and the prevalence of obesity was 11% in women and 15% in men. No significant secular trends were observed for WHR, but there was an upward trend in prevalence of WHR>0.85 in women. A decreased prevalence of smoking in both sexes was observed together with an increase in reported leisure time physical activity. No significant secular trends were observed in rates of self-reported diabetes, although the risk of diabetes attributable to obesity was 24%. CONCLUSION: The results indicate that 25-64-y-olds in the recent survey were more overweight and obese than earlier studied MONICA participants. The increase in BMI was more pronounced in men while abdominal obesity increased principally in women. Although obesity and overweight are clearly important risk factors for type 2 diabetes, the number of diabetics remains low and any secular increase is not yet apparent.
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  • Berggren, Ulf, 1948, et al. (author)
  • Dopamine D2 Receptor Genotype Is Associated with Increased Mortality at a 10-Year Follow-up of Alcohol-Dependent Individuals.
  • 2010
  • In: Alcohol and alcoholism. - : Oxford University Press (OUP). - 1464-3502 .- 0735-0414. ; 45:1, s. 1-5
  • Journal article (peer-reviewed)abstract
    • AIMS: Because the TAQ1 A1 allele may be associated with alcohol-related medical illnesses, and medical illnesses in alcohol-dependent individuals are associated with increased mortality, we test the hypothesis that the TAQ1 A1 allele of the DRD2 gene is associated with increased mortality in alcohol-dependent individuals. METHODS: Following an index treatment episode, a 10-year follow-up study in 366 alcohol-dependent individuals was performed. The TAQ1 A1/A2 DRD2 genotype and allele frequencies were compared between those deceased and those still living at the 10-year point. In addition, the genotype and allele frequencies of these alcohol-dependent individuals were compared to that in 578 control subjects. RESULTS: The prevalence of the A1 allele differed between the deceased and living patients and the controls: 47% of the deceased were A1+, compared to 37% of the living patients and 32% of the controls. The frequency of the TAQ1 A1/A2 genotype also differed between the groups. Thus, 43% had the A1/A2 genotype in comparison with 32% in the living patients and 29% in the controls. The TAQ 1 A1 allele frequency differed between the groups. The frequency of A1 allele was 25% in the deceased patients compared to 21% in the living patients and 17% in the controls. CONCLUSION: The TAQ I A1 allele of the DRD2 gene (or DRD2 gene region) was associated with increased mortality over a 10-year period in alcohol-dependent individuals.
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  • Berggren, Ulf, 1948, et al. (author)
  • The taqI DRD2 A1 allele is associated with alcohol-dependence although its effect size is small
  • 2006
  • In: Alcohol. - : Oxford University Press (OUP). - 0735-0414. ; 41:5, s. 479-85
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Numerous studies of the relationship between the TaqIA DRD2 A1 allele and alcohol-dependence have been performed and many of these have shown an association whereas others have not (Noble, 2003). This has consequently generated some controversy as to whether such an association actually exists (Noble, 2003). In the two recent meta-analyses by Noble (2003) and Young et al. (2004) some very important methodological issues have been discussed, which need to be addressed in forthcoming studies. Thus, the sample size is of great importance. In case-control studies it has been estimated that to detect the role of genes with small effect size of approximately 2, which is in the range of the DRD2 A1 allele-alcoholism relationship, case-control sets of 300-400 subjects are necessary (Noble, 2003). METHODS: In the present study, we have consequently recruited a large number of subjects, 375 alcohol-dependent individuals, who were treated as inpatients for alcohol withdrawal symptoms and out of these 357 could be evaluated. As controls, 578 individuals screened and 254 individuals unscreened for alcohol consumption were used. Thus, the total number of subjects was 1217. RESULTS: In the present study, in which the TaqI A1/A2 DRD2 polymorphism was in Hardy-Weinberg equilibrium in the patient group and the two control groups, we found that the TaqI DRD2 A1/A2 genotype frequency differed significantly between the alcohol-dependent group and both the total and screened control groups. Furthermore, the TaqI DRD2 A1 allele frequency was significantly overrepresented in the alcohol-dependent subjects as compared with both the total and screened control groups. The odds ratio for alcohol-dependency being associated with the A1 allele was 1.34. CONCLUSIONS: Consequently, the findings in this study lend further support to the notion of an association between the DRD2 A1 allele and alcohol-dependence, although the effect size of the DRD2 A1 allele is small.
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20.
  • Biong, A. S., et al. (author)
  • Intake of dairy fat and dairy products, and risk of myocardial infarction: A case-control study
  • 2008
  • In: International Journal of Food Sciences and Nutrition. - : Informa UK Limited. - 0963-7486 .- 1465-3478. ; 59:2, s. 1-11
  • Journal article (peer-reviewed)abstract
    • The role of dairy fat in the aetiology of myocardial infarction (MI) is controversial. The aim of this study was to evaluate the association between intake of dairy fat and dairy products, and risk of a first acute MI. A total of 111 MI patients with a first acute MI and 107 population controls (men and women, age 45-75 years) were studied. Diet was assessed using a 180-item food frequency questionnaire. The MI cases had higher intake of total fat, but lower intake of saturated fat and dairy fat than the control persons. No effect of dairy fat or saturated fat on the odds ratio for MI was observed, however. A significant inverse trend in odds of MI for intake of cheese was observed, but the trend was no longer significant after adjustment for smoking. The results suggest that intake of fat from dairy products may not be associated with increased risk of having a first MI. The healthy control persons had a diet that differed from the diet of the MI patients in many aspects, and dairy products were a part of this diet. This may have protected them from having a first MI.
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21.
  • Biong, A. S., et al. (author)
  • Intake of milk fat, reflected in adipose tissue fatty acids and risk of myocardial infarction: a case-control study
  • 2006
  • In: Eur J Clin Nutr. - 0954-3007. ; 60:2, s. 236-44
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: To study the association between content of fatty acids from milk fat (14:0, 15:0 and 17:0) in adipose tissue and risk of a first myocardial infarction (MI). DESIGN AND SUBJECTS: A case-control study with 99 patients and 98 population controls both men and postmenopausal women, age 45-75 year. Adipose tissue fatty acids were determined by gas-liquid chromatography. RESULTS: The content of 14:0, 14:1, 15:0, 17:0 and 17:1 were all significantly higher in adipose tissue of controls than of the patients. Age and sex adjusted odds ratios (OR) for MI were significantly reduced with increasing quartiles of 14:0, 14:1, 15:0 and 17:1 in adipose tissue, but except for 15:0 (OR = 0.36, 95% CI 0.13-0.99), the trend was no longer significant after further adjustment for waist-to-hip ratio, smoking and family history for coronary heart disease. Correlations between 14:0 and 15:0 in adipose tissue, and waist-to-hip ratio were significantly negative (r = -0.22 for both, P < 0.01). CONCLUSION: Our study suggests that intake of dairy fat or some other component of dairy products, as reflected by C15:0 as marker in adipose tissue, may protect persons at increased risk from having a first MI, and that the causal effects may rely on other factors than serum cholesterol. SPONSORSHIP: Throne Holst's foundation for Nutrition Research, Research Council of Norway, The Norwegian Association of Margarine Producers, DeNoFa Fabriker A/S, TINE BA.
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22.
  • Bodegard, J., et al. (author)
  • Possible angina detected by the WHO angina questionnaire in apparently healthy men with a normal exercise ECG: coronary heart disease or not? A 26 year follow up study
  • 2004
  • In: Heart. - 1468-201X. ; 90:6, s. 627-32
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: To determine whether men with possible angina (from their responses to the World Health Organization angina questionnaire) but a normal exercise ECG differ in long term rates of coronary heart disease events from men with no symptoms of angina. DESIGN: During 1972-75, 2014 apparently healthy men aged 40-59 years underwent an examination programme including case history, clinical examination, exercise ECG to exhaustion, and various other tests. All men completed the WHO angina questionnaire. SUBJECTS: Of 2014 men, 68 had possible angina, 1831 had no symptoms of angina, and 115 were excluded because they had definite angina or pathological exercise ECGs. All 68+1831 had normal exercise ECGs and none developed chest pain during the exercise test. RESULTS: At 26 years, men with possible angina had a coronary heart disease mortality of 25.0% (17/68) v 13.8% (252/1831) among men with no symptoms of angina (p < 0.013). They also had a higher incidence of coronary artery bypass grafting (CABG) (p < 0.0004) and acute myocardial infarction (p < 0.026). The excess coronary heart disease mortality among men with possible angina only started after 15 years, whereas differences in CABG/acute myocardial infarction started early. Multivariate analysis including well recognised coronary heart disease risk factors showed that possible angina was an independent risk factor (relative risk 1.79, 95% confidence interval 1.26 to 2.10). CONCLUSIONS: Men with possible angina, even with a normal exercise test, have a greater risk of dying from coronary heart disease, having an acute myocardial infarct, or needing a CABG than age matched counterparts with no symptoms of angina.
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23.
  • Bodegard, J., et al. (author)
  • Symptom-limited exercise testing, ST depressions and long-term coronary heart disease mortality in apparently healthy middle-aged men
  • 2004
  • In: Eur J Cardiovasc Prev Rehabil. - : Oxford University Press (OUP). - 1741-8267. ; 11:4, s. 320-7
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Previous studies have shown that ST depressions > or =1.0 mm during or post-exercise increase long-term risk of dying from coronary heart disease (CHD), the need for coronary artery bypass grafting (CABG) or the development of acute myocardial infarction (AMI) in healthy men. In the present prospective cohort study we investigate whether less marked ST depressions may influence CHD mortality, incidence of AMI, the need for a CABG or having a non-fatal stroke. METHODS: During 1972-75, 2014 men aged 40-59 years, free from somatic diseases and not using any drugs, underwent an examination programme including case history, clinical examination, various blood tests and a symptom-limited exercise ECG-test. ECG was registered during exercise and at 30 s, 1, 2, 3 and 5 min post-exercise. The possible prognostic impact of ST-changes of 0.50-0.99 mm and > or =1.00 mm compared with normal ST-segments were studied separately and combined. Horizontal, down-sloping and slowly up-sloping ST-segment patterns were combined. RESULTS: After adjustment for age, smoking, blood pressure, cholesterol, maximal heart rate, left ventricular hypertrophy and physical fitness ST depressions > or =0.50 mm--during and/or post-exercise--were associated with a 1.47-fold [95% confidence interval (CI) 1.10-1.95], and 1.54-fold (95% CI of 1.17-2.04) increased 26 years risk of CHD-mortality, respectively. The same ST-changes also increased 22 years risk of developing non-fatal AMI or needing CABG but not developing non-fatal stroke. CONCLUSIONS: Even an ST depression > or =0.50 mm during and/or after exercise increases the long-term risk of CHD-death, developing an AMI or needing CABG. No association was found between ST-changes and incidence of non-fatal strokes.
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24.
  •  
25.
  • Erikssen, G., et al. (author)
  • Exercise testing of healthy men in a new perspective: from diagnosis to prognosis
  • 2004
  • In: Eur Heart J. - 0195-668X. ; 25:11, s. 978-86
  • Journal article (peer-reviewed)abstract
    • AIM: It has recently been suggested that exercise testing may be more valuable prognostically than it is diagnostically in apparently healthy subjects. We wanted to compare the accuracy of CHD risk assessment based on classical risk factors with an assessment also based on multiple exercise test parameters. METHODS AND RESULTS: In 1972-75, 2014 apparently healthy men aged 40-60 had a symptom limited exercise test during a cardiovascular survey. Three hundred died from CHD during 26 years of follow-up. Compared to Cox regression models solely including classical risk factors (CRF), models also including multiple exercise test parameters (CRF+X) were clearly superior (P < 0.0001). Risk scores were computed based on the models. CRF and CRF+X risk scores often differed markedly; CRF+X scores were generally most reliable in both the high and low risk range. In smokers with cholesterol >6.5 mmol/l (n = 470), the CRF and CRF+X models identified 67 vs. 110 men at the highest CHD risk level according to European guidelines (34.2% vs. 38.2% CHD mortality). Three in five CRF+X-identified smokers with cholesterol >6.5 mmol/l had CHD mortality similar to the mean of all 2014 men. CONCLUSION: Integration of multiple exercise test parameters and conventional risk factors improved CHD risk assessment substantially--especially in smokers with high cholesterol.
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