| 1. |
- Brito, Ema C, 1961-, et al.
(författare)
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PPARGC1A sequence variation and cardiovascular risk-factor levels : a study of the main genetic effects and gene x environment interactions in children from the European youth heart study
- 2009
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 52:4, s. 609-613
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: The PPARGC1A gene coactivates multiple nuclear transcription factors involved in cellular energy metabolism and vascular stasis. In the present study, we genotyped 35 tagging polymorphisms to capture all common PPARGC1A nucleotide sequence variations and tested for association with metabolic and cardiovascular traits in 2,101 Danish and Estonian boys and girls from the European Youth Heart Study, a multicentre school-based cross-sectional cohort study. METHODS: Fasting plasma glucose concentrations, anthropometric variables and blood pressure were measured. Habitual physical activity and aerobic fitness were objectively assessed using uniaxial accelerometry and a maximal aerobic exercise stress test on a bicycle ergometer, respectively. RESULTS: In adjusted models, nominally significant associations were observed for BMI (rs10018239, p = 0.039), waist circumference (rs7656250, p = 0.012; rs8192678 [Gly482Ser], p = 0.015; rs3755863, p = 0.02; rs10018239, beta = -0.01 cm per minor allele copy, p = 0.043), systolic blood pressure (rs2970869, p = 0.018) and fasting glucose concentrations (rs11724368, p = 0.045). Stronger associations were observed for aerobic fitness (rs7656250, p = 0.005; rs13117172, p = 0.008) and fasting glucose concentrations (rs7657071, p = 0.002). None remained significant after correcting for the number of statistical comparisons. We proceeded by testing for gene x physical activity interactions for the polymorphisms that showed nominal evidence of association in the main effect models. None of these tests was statistically significant. CONCLUSIONS/INTERPRETATION: Variants at PPARGC1A may influence several metabolic traits in this European paediatric cohort. However, variation at PPARGC1A is unlikely to have a major impact on cardiovascular or metabolic health in these children.
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| 2. |
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| 3. |
- Franks, Paul, et al.
(författare)
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Physical activity energy expenditure may mediate the relationship between plasma leptin levels and worsening insulin resistance independently of adiposity.
- 2007
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Ingår i: J Appl Physiol. - : American Physiological Society. - 8750-7587. ; 102:5, s. 1921-6
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Tidskriftsartikel (refereegranskat)abstract
- Leptin regulates a constellation of neuroendocrine processes that control energy homeostasis. The infusion of leptin in rodents lacking endogenous leptin promotes physical activity energy expenditure (PAEE) and improves insulin signaling, whereas hyperleptinemia is associated with physical inactivity and insulin resistance (IR). We tested whether baseline leptin levels predict changes in PAEE and IR over time, independent of obesity. We also assessed whether the relationship between leptin and change in IR is mediated by PAEE. The population consisted of 288 nondiabetic UK Caucasian adults (mean age: 49.4 yr; SD: 0.7 yr), in whom leptin, insulin, glucose, PAEE (via heart rate monitoring with individual calibration by indirect calorimetry), and anthropometric characteristics had been measured at baseline and 5 yr later. In linear regression models, baseline leptin levels inversely predicted follow-up PAEE ( P = 0.033). On average, individuals with low leptin levels (below sex-specific median) increased their daily activity 35% more during the 5-yr follow-up period than those with above-median leptin levels. Baseline leptin level also predicted worsening IR (fasting, 30-min, and 2-h insulins, and homeostasis model assessment-IR; all P < 0.01). Associations were independent of potential confounders, such as adiposity, age, and sex. Including baseline PAEE as a cofactor in the leptin-insulin models reduced the strength (1–4% reduction) and significance of the associations, suggesting that PAEE mediates the leptin-insulin relationships. Hyperleptinemia predicts a relative decline in PAEE and worsening insulin resistance, possibly via shared molecular pathways.
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| 5. |
- Olsen, Rikke K J, et al.
(författare)
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ETFDH mutations as a major cause of riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency.
- 2007
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Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; 130:Pt 8, s. 2045-54
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Tidskriftsartikel (refereegranskat)abstract
- Multiple acyl-CoA dehydrogenation deficiency (MADD) is a disorder of fatty acid, amino acid and choline metabolism that can result from defects in two flavoproteins, electron transfer flavoprotein (ETF) or ETF: ubiquinone oxidoreductase (ETF:QO). Some patients respond to pharmacological doses of riboflavin. It is unknown whether these patients have defects in the flavoproteins themselves or defects in the formation of the cofactor, FAD, from riboflavin. We report 15 patients from 11 pedigrees. All the index cases presented with encephalopathy or muscle weakness or a combination of these symptoms; several had previously suffered cyclical vomiting. Urine organic acid and plasma acyl-carnitine profiles indicated MADD. Clinical and biochemical parameters were either totally or partly corrected after riboflavin treatment. All patients had mutations in the gene for ETF:QO. In one patient, we show that the ETF:QO mutations are associated with a riboflavin-sensitive impairment of ETF:QO activity. This patient also had partial deficiencies of flavin-dependent acyl-CoA dehydrogenases and respiratory chain complexes, most of which were restored to control levels after riboflavin treatment. Low activities of mitochondrial flavoproteins or respiratory chain complexes have been reported previously in two of our patients with ETF:QO mutations. We postulate that riboflavin-responsive MADD may result from defects of ETF:QO combined with general mitochondrial dysfunction. This is the largest collection of riboflavin-responsive MADD patients ever reported, and the first demonstration of the molecular genetic basis for the disorder.
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| 6. |
- Andersson, Lena, 1965, et al.
(författare)
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Can access to psychiatric health care explain regional differences in disability pension with psychiatric disorders?
- 2007
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Ingår i: Soc Psychiatry Psychiatr Epidemiol. - : Springer Science and Business Media LLC. - 0933-7954 .- 1433-9285. ; 42:5, s. 366-71
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Psychiatric disorders are a serious public health problem, especially as many psychiatric disorders begin early in life. Disability pension (DP) with psychiatric diagnoses has, since the mid 1990s, increased in several European countries and regional differences within countries have emerged. It is not clear whether these regional differences are associated with differences in access to psychiatric health care. AIM: The aim of this study was to investigate whether regional differences in DP with psychiatric diagnoses in Norway were associated with differences in psychiatric service provision (the number of staff employed and psychiatric beds available). METHOD: The study population consisted of individuals aged 16-67 years living in Norway (n = 4,348,410) and six southern regions. Included cases were individuals who were granted a DP with a psychiatric diagnosis between 1 January and 31 December 1990, 1995 or 2000. Mental retardation was excluded. Data on cases were collected from the National Insurance Administration and data on psychiatric health care staff and beds was collected from Specialist Health Service, Statistics Norway. Regression models were used to calculate incidence rate ratios (IRR) with 95% confidence intervals (CI) using Norway as reference. RESULTS: Staffing levels (per 10,000 inhabitants) did not differ substantially between the regions, with the exception of Oslo that had about 70% higher numbers of staff employed. In regression analyses controlling for numbers of psychiatric staff and beds, regional differences in DP remained. Both men and women in the semi rural regions Aust-Agder and Vest-Agder were significantly more likely to receive a DP with a psychiatric diagnosis, while the IRR for DP was reduced in Ostfold. Different psychiatric staff groups were associated with increased or decreased rates of DP. The adjusted IRR between number of psychiatric staff (man-years of staff per 10,000 inhabitants) and DP with psychiatric diagnoses were: 1.23 (1.18-1.29) for psychologists, 1.13 (1.04-1.23) for physicians, 1.03 (1.00-1.07) for nurses and 0.84 (0.80-0.88) for auxiliary nurses. Furthermore, increased numbers of beds were associated with DP with a psychiatric diagnosis (IRR 2.86 (2.03-4.05) for 100 beds/10,000 population). CONCLUSION: Psychiatric provision (in terms of both staff and beds) was associated with the incidence of DP with psychiatric diagnoses but regional differences in provision did not explain the regional differences in DP with a psychiatric diagnosis. Future work needs to examine whether differences in case detection and case management are associated with regional differences in DP with psychiatric diagnoses.
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| 7. |
- Andersson, Lena, 1965, et al.
(författare)
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Disability pension for psychiatric disorders: Regional differences in Norway 1988-2000
- 2006
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Ingår i: Nord J Psychiatry. ; 60:4, s. 255-62
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to describe regional differences in the incidence of disability pensions (DPs) with psychiatric diagnoses, and to determine whether these differences were related to age and/or gender. We compared the incidence rates of new DPs including all diagnoses, with DP with psychiatric diagnoses in Norwegian regions from 1988 to 2000. The population at risk was all individuals aged 16-67 in each year. Individuals already on DP were excluded. Cases were collected from the Norwegian National Insurance Administration. The results showed that the incidence rate ratio (IRR; Norway reference) for DP with psychiatric diagnoses was most elevated for men 1.41 (95% CI 1.27-1.58) and women 1.48 (95% CI 1.34-1.64) living in the most rural region. Men in the urban area had a higher IRR, 1.33 (95% CI 1.26-1.40), than urban women, 1.02 (95% CI 0.96-1.07). The incidence more than doubled in the youngest age group (16-29 years) and decreased in the oldest age group (60-67 years) between 1988 and 2000. The findings conclude that individuals living in semi-rural regions of Norway are more likely to receive a DP with a psychiatric diagnosis than those living in urban areas. Large gender differences were found in the urban area. Further research is needed to investigate the impact of the psychiatric healthcare system and access to rehabilitation on psychiatric disability.
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| 8. |
- Hensing, Gunnel, 1956, et al.
(författare)
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Increase in sickness absence with psychiatric diagnosis in Norway: a general population-based epidemiologic study of age, gender and regional distribution
- 2006
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Ingår i: BMC Med. - : Springer Science and Business Media LLC. - 1741-7015. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim of this study was to assess the incidence of sickness absence with psychiatric diagnoses from 1994-2000, and the distribution across gender, age groups, diagnostic groups and regions in a general population. METHODS: The population at risk was defined as all individuals aged 16-66 years who were entitled to sickness benefits in 1994, 1996, 1998 and 2000 (n = 2,282,761 in 2000). All individuals with a full-time disability pension were excluded. The study included approximately 77% of the Norwegian population aged 16-66 years. For each year, the study base started on 1 January and ended on 31 December. Individuals that were sick-listed for more than 14/16 consecutive days with a psychiatric diagnosis on their medical certificate were selected as cases. Included in this study were data for Norway, the capital city Oslo and five regions in the southeast of the country. RESULTS: Sickness absence with psychiatric diagnoses increased in all age groups, in women and men, and in all regions. At the national level, the cumulative incidence increased in women from 1.7% in 1994 to 4.6% in 2000, and in men from 0.8% in 1994 to 2.2% in 2000. The highest cumulative incidence was found in middle-aged women and men (30-59 years). Women had a higher incidence than men in all stratification groups. The cumulative incidences in 2000 varied between 4.6% to 5.6% in women in the different regions, and for men the corresponding figures were 2.1% to 3.2%. Throughout the four years studied, women in Oslo had more than twice as high incidence levels of sickness absence with alcohol and drug diagnoses as the country as a whole. There were some differences between regions in sickness absence with specific psychiatric diagnoses, but they were small and most comparisons were non-significant. CONCLUSION: Sickness absence with psychiatric diagnoses increased between 1994 and 2000 in Norway. The increase was highest in the middle-aged, and in women. Few regional differences were found. That the increase pervaded all stratification groups supports general explanations of the increase, such as changes in attitudes to psychiatric disorders in both patients and doctors, and increased mental distress probably associated with societal changes at a more structural level.
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| 9. |
- Ihlebaek, C., et al.
(författare)
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Prevalence of low back pain and sickness absence: a "borderline" study in Norway and Sweden
- 2006
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Ingår i: Scand J Public Health. - 1403-4948. ; 34:5, s. 555-8
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Low back pain (LBP) is a major public health problem in both Norway and Sweden. The aim of the study was to estimate the prevalence of LBP and sickness absence due to LBP in two neighbouring regions in Norway and Sweden. The two areas have similar socioeconomic status, but differ in health benefit systems. METHODS: A representative sample of 1,988 adults in Norway and 2,006 in Sweden completed questionnaires concerning LBP during 1999 and 2000. For this study only individuals in part or full time jobs, (n = 1,158 in Norway and n = 1,129 in Sweden) were included. RESULTS: In Norway the lifetime prevalence was 60.7% and in Sweden 69.6%, the one-year prevalence was 40.5% and 47.2%, and the point prevalence 13.4% and 18.2% respectively. There was a significantly higher risk of reporting LBP in Sweden, even after controlling for gender, age, education, and physical workload. There was no difference in risk of self-certified short-term sickness absence (1-3 days), but it was a 40% lower risk of sickness absence with medical sickness certification in Sweden compared with Norway. CONCLUSION: The prevalence of LBP was higher in the Swedish area than in the Norwegian. The risk of self-certified sickness absence, however, showed no differences and the risk of medically certified sickness absence was lower in the Swedish area. This contradiction might partly be explained by the economical "disincentives" in the Swedish health compensation system.
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| 10. |
- Vimaleswaran, Karani S, et al.
(författare)
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Absence of association between the INSIG2 gene polymorphism (rs7566605) and obesity in the European Youth Heart Study (EYHS)
- 2009
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Ingår i: Obesity. - : Wiley. - 1930-7381 .- 1930-739X. ; 17:7, s. 1453-1457
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Tidskriftsartikel (refereegranskat)abstract
- The first genome-wide association study for BMI identified a polymorphism, rs7566605, 10 kb upstream of the insulin-induced gene 2 (INSIG2) transcription start site, as the most significantly associated variant in children and adults. Subsequent studies, however, showed inconsistent association of this polymorphism with obesity traits. This polymorphism has been hypothesized to alter INSIG2 expression leading to inhibition of fatty acid and cholesterol synthesis. Hence, we investigated the association of the INSIG2 rs7566605 polymorphism with obesity- and lipid-related traits in Danish and Estonian children (930 boys and 1,073 girls) from the European Youth Heart Study (EYHS), a school-based, cross-sectional study of pre- and early pubertal children. The association between the polymorphism and obesity traits was tested using additive and recessive models adjusted for age, age-group, gender, maturity and country. Interactions were tested by including the interaction terms in the model. Despite having sufficient power (98%) to detect the previously reported effect size for association with BMI, we did not find significant effects of rs7566605 on BMI (additive, P = 0.68; recessive, P = 0.24). Accordingly, the polymorphism was not associated with overweight (P = 0.87) or obesity (P = 0.34). We also did not find association with waist circumference (WC), sum of four skinfolds, or with total cholesterol, triglycerides, low-density lipoprotein, or high-density lipoprotein. There were no gender-specific (P = 0.55), age-group-specific (P = 0.63) or country-specific (P = 0.56) effects. There was also no evidence of interaction between genotype and physical activity (P = 0.95). Despite an adequately powered study, our findings suggest that rs7566605 is not associated with obesity-related traits and lipids in the EYHS.Obesity (2009) doi:10.1038/oby.2008.650.
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| 11. |
- Vimaleswaran, Karani S., et al.
(författare)
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Habitual Energy Expenditure Modifies the Association Between NOS3 Gene Polymorphisms and Blood Pressure
- 2008
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Ingår i: American Journal of Hypertension. - : Oxford University Press. - 0895-7061 .- 1941-7225. ; 21:3, s. 297-302
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Tidskriftsartikel (refereegranskat)abstract
- Background: The endothelial nitric-oxide synthase (NOS3) gene encodes the enzyme (eNOS) that synthesizes the molecule nitric oxide, which facilitates endothelium-dependent vasodilation in response to physical activity. Thus, energy expenditure may modify the association between the genetic variation at NOS3and blood pressure.Methods: To test this hypothesis, we genotyped 11 NOS3 polymorphisms, capturing all common variations, in 726 men and women from the Medical Research Council (MRC) Ely Study (age (mean ± s.d.): 55 ± 10 years, body mass index: 26.4 ± 4.1 kg/m2). Habitual/non-resting energy expenditure (NREE) was assessed via individually calibrated heart rate monitoring over 4 days.Results: The intronic variant, IVS25+15 [G→A], was significantly associated with blood pressure; GG homozygotes had significantly lower levels of diastolic blood pressure (DBP) (−2.8 mm Hg; P = 0.016) and systolic blood pressure (SBP) (−1.9 mm Hg; P = 0.018) than A-allele carriers. The interaction between NREE and IVS25+15 was also significant for both DBP (P = 0.006) and SBP (P = 0.026), in such a way that the effect of the GG-genotype on blood pressure was stronger in individuals with higher NREE (DBP: −4.9 mm Hg, P = 0.02. SBP: −3.8 mm Hg, P= 0.03 for the third tertile). Similar results were observed when the outcome was dichotomously defined as hypertension.Conclusions: In summary, the NOS3 IVS25+15 is directly associated with blood pressure and hypertension in white Europeans. However, the associations are most evident in the individuals with the highest NREE. These results need further replication and have to be ideally tested in a trial before being informative for targeted disease prevention. Eventually, the selection of individuals for lifestyle intervention programs could be guided by knowledge of genotype.
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