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- Landgren, Sara, 1980, et al.
(författare)
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Genetic variation of the ghrelin signaling system in females with severe alcohol dependence
- 2010
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Ingår i: Alcoholism: Clinical and Experimental Research. - : Wiley. - 0145-6008 .- 1530-0277. ; 34:9, s. 1519-1524
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Tidskriftsartikel (refereegranskat)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.
(författare)
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The ghrelin signalling system is involved in the consumption of sweets.
- 2011
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Ingår i: PLos One. - : Public Library of Science (PLoS). - 1932-6203. ; 6:3
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Tidskriftsartikel (refereegranskat)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. |
- Aminoff, A, et al.
(författare)
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Allele-specific regulation of MTTP expression influences the risk of ischemic heart disease.
- 2010
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Ingår i: Journal of lipid research. - 0022-2275 .- 1539-7262. ; 51:1, s. 103-11
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Tidskriftsartikel (refereegranskat)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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| 6. |
- Ericson Sjöström, Monica, et al.
(författare)
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GP and patient predictions of sick-listing duration: How well do they correspond? A prospective observational study
- 2014
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Ingår i: Scandinavian Journal of Primary Health Care. - : Informa UK Limited. - 0281-3432 .- 1502-7724. ; 32:2, s. 73-77
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To explore how well physicians and patients predict sick-listing duration and the correspondence between their respective predictions. To study possible gender differences concerning prediction accuracy. Design. Prospective observational study. Setting. Two medium-sized primary care centres (PCC) in western Sweden. Subjects. GPs at the PCCs and attending patients sick-listed for > 14 days. Main outcome measures. Sick-listing duration; patients' and GPs' predictions of the total duration of the individual patient's sick-listing. Results. A total of 127 patients (93 women, 34 men, mean age 45 years) and 10 GPs participated in the study. Neither the GPs nor the patients were able to predict the interval until return to work with high accuracy. The GPs' and the patients' perceptions concurred in only 26% of cases. There was a significant difference in the correspondence between the GPs' and patients' respective predictions of sick-listing duration compared with the actual duration. GPs' predictions were more accurate for medium-length duration (1.5-6 months), while patients' predictions were more accurate for long-duration (> 6 months) sick-listing. Patients with less education predicted long duration of sick-listing more accurately than those with more education. There was no significant difference between male and female patients' accuracy of prediction, or between GPs' accuracy of prediction of male vs. female patients' sick-listing duration. Conclusions. Prediction of total sick-listing duration was hard for both GP and patient; their respective predictions corresponded in only one-quarter of the cases. No gender differences were observed in the accuracy of prediction.
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| 7. |
- Gustavsson, Jaana, 1974, et al.
(författare)
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Interaction of apolipoprotein E genotype with smoking and physical inactivity on coronary heart disease risk in men and women.
- 2012
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Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 220:2, s. 486-492
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Apolipoprotein E genotype (APOE) polymorphism affects lipid levels and coronary heart disease (CHD) risk. However, these associations may be modified by lifestyle factors. Therefore, we studied whether smoking, physical inactivity or overweight interact with APOE on cholesterol levels and CHD risk. METHODS: Combining two Swedish case-control studies yielded 1735 CHD cases and 4654 population controls (3747 men, 2642 women). Self-reported questionnaire lifestyle data included smoking (ever [current or former regular] or never) and physical inactivity (mainly sitting leisure time). We obtained LDL cholesterol levels and APOE genotypes. CHD risk was modelled using logistic regression to obtain odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for relevant covariates. RESULTS: Smoking interacted with APOE on CHD risk; adjusted ORs for ever versus never smoking were 1.45 (95% CI 1.00-2.10) in ɛ2 carriers, 2.25 (95% CI 1.90-2.68) in ɛ3 homozygotes and 2.37 (95% CI 1.85-3.04) in ɛ4 carriers. Female ɛ4 carriers had OR 3.62 (95% CI 2.32-5.63). The adjusted ORs for physical inactivity were 1.09 (95% CI 0.73-1.61), 1.34 (95% CI 1.12-1.61), and 1.79 (95% CI 1.38-2.30) in ɛ2, ɛ3ɛ3 and ɛ4 groups, respectively. No interaction was seen between overweight and APOE for CHD risk, or between any lifestyle factor and APOE for LDL cholesterol levels. CONCLUSION: The APOE ɛ2 allele counteracted CHD risk from smoking in both genders, while the ɛ4 allele was seen to potentiate this risk mainly in women. Similar ɛ2 protection and ɛ4 potentiation was suggested for CHD risk from physical inactivity.
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| 8. |
- Mehlig, Kirsten, 1964, et al.
(författare)
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CETP TaqIB genotype modifies the association between alcohol and coronary heart disease: The INTERGENE case-control study
- 2014
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Ingår i: Alcohol. - : Elsevier BV. - 0741-8329. ; 48:7, s. 695-700
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Tidskriftsartikel (refereegranskat)abstract
- Alcohol consumption at moderate levels has been associated with decreased risk of coronary heart disease (CHD). However, the cardio-protective effect of alcohol may be restricted to subjects with a particular genotype of the cholesteryl ester transfer protein (CETP) polymorphism. There is evidence for this from one study in men, but the finding has not been confirmed since. The present study specifically re-examines the potential modification of the association between alcohol consumption and CHD by the CETP TaqIB (rs708272) polymorphism in a sample including both men and women. The INTERGENE case-control study consists of 618 patients with CHD and 2921 control subjects, of whom 19% were homozygous for the CETP TaqIB B2 allele. Alcohol consumption was categorized into sex-specific tertiles of ethanol intake, with non-drinkers constituting a separate category. Logistic regression was used to determine the association between CHD with genotype, ethanol intake, and their interaction. Participants with intermediate ethanol intake (2nd tertile) had lower risk of CHD than those with low ethanol intake (odds ratio [OR] = 0.65; 95% confidence interval [Cl] 0.50-0.85). The strongest protective association was seen in the CETP TaqIB B2 homozygotes for intermediate vs. low ethanol intake (odds ratio OR = 0.21; 95% CI 0.10-0.44). The interaction between ethanol intake and genotype was statistically significant (p = 0.008), and of similar size in men and women though significant only in men (p = 0.01). The effect modification could not be explained by differences in lifestyle, socioeconomics, or alcohol-related biological variables such as HDL-cholesterol. Our study is the first to replicate previous findings of an effect modification in men. It gives only suggestive results for women, possibly due to the small number of female cases (n = 165). The prevented fraction for the favorable combination of genotype and alcohol consumption is about 6%, a value suggesting that the cardio-protective effect of moderate alcohol consumption applies only to a small segment of the general population. (C) 2014 The Authors. Published by Elsevier Inc.
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| 9. |
- Mehlig, Kirsten, 1964, et al.
(författare)
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The association between plasma homocysteine and coronary heart disease is modified by the MTHFR 677C>T polymorphism.
- 2013
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Ingår i: Heart (British Cardiac Society). - : BMJ. - 1468-201X .- 1355-6037. ; 99:23, s. 1761-1765
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Tidskriftsartikel (refereegranskat)abstract
- An elevated level of total plasma homocysteine (tHcy) has been associated with risk of coronary heart disease (CHD). The level of tHcy is affected by lifestyle, in addition to genetic predisposition. The methylene tetrahydrofolate reductase (MTHFR) 677C>T polymorphism (rs1801133) is among the strongest genetic predictors of tHcy. We examined whether the association between tHcy and CHD is modified by the MTHFR 677C>T polymorphism.
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| 10. |
- Strandhagen, Elisabeth, 1960, et al.
(författare)
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Selection bias in a population study with registry linkage – potential effect on social gradient in cardiovascular risk
- 2010
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Ingår i: European Journal of Epidemiology. - 1573-7284. ; 25:3, s. 163-172
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Tidskriftsartikel (refereegranskat)abstract
- Non-participation in population studies is likely to be a source of bias in many types of epidemiologic studies, including those describing social disparities in health. The objective of this paper is to present a non-attendance analysis evaluating the possible impact of selection bias, when investigating the association between education level and cardiovascular risk factors. Data from the INTERGENE research programme including 3,610 randomly selected individuals aged 25-74 (1,908 women and 1,702 men), in West Sweden were used. Only 42% of the invited population participated. Non-attendance analyses were done by comparing data from official registries (Statistics Sweden) covering the entire invited study population. This analysis revealed that participants were more likely to be women, have university education, high income, be married and of Nordic origin compared to non-participants. Among participants, all health behaviours studied were significantly related to education. Physical activity, alcohol use and breakfast consumption were higher in the more educated group, while there were more smokers in the less educated group. Central obesity, obesity and hypertension were also significantly associated with lower education level. Weaker associations were observed for blood lipids, diabetes, high plasma glucose level and perceived stress. The socio-demographic differences between participants and non-participants indicated by the register analysis imply potential biases in epidemiological research. For instance, the positive association between education level and frequent alcohol consumption, may, in part be explained by participation bias. For other risk factors studied, an underestimation of the importance of low socioeconomic status may be more likely.
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