Significant associations of the rs2943634 (2q36.3) genetic polymorphism with adiponectin, high density lipoprotein cholesterol and ischemic stroke |
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Authors: | Arregui Maria Fisher Eva Knüppel Sven Buijsse Brian di Giuseppe Romina Fritsche Andreas Corella Dolores Willich Stefan N Boeing Heiner Weikert Cornelia |
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Institution: | a Department of Epidemiology, German Institute of Human Nutrition (DIfE), Potsdam-Rehbruecke, 14558 Nuthetal, Germanyb Administrative Office of the Commission on Genetic Testing, Robert Koch-Institute, Berlin, Germanyc Department of Internal Medicine, Division of Endocrinology, Diabetology, Nephrology, Vascular Disease and Clinical Chemistry, University of Tübingen, Tübingen, Germanyd Department of Preventive Medicine and CIBER Fisiopatología de la Obesidad y Nutrición, School of Medicine, University of Valencia, Valencia, Spaine Institute for Social Medicine, Epidemiology, and Health Economics, Charité University Medical Center, Berlin, Germany |
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Abstract: | Backgroundrs2943634 C/A single nucleotide polymorphism (SNP), located in a non coding region of chromosome 2q36.3, has been associated with coronary artery disease in two genome wide association studies. Our goal was to investigate its relation with myocardial infarction (MI) and ischemic stroke (IS), as well as with 12 intermediate risk phenotypes, in a population-based prospective cohort study.Methodsrs2943634 was genotyped in a case-cohort study including a random sample of 1891 individuals (subcohort) and all incident MI (n = 211) and IS (n = 144) cases during a mean follow-up of 8.2 ± 2.2 years, nested within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort comprising 27,548 middle-aged men and women.Resultsrs2943634 minor allele (A) was associated in an additive fashion with lower risk of IS but not with MI hazard ratio (HR) = 0.66; 95% confidence interval (CI): 0.50-0.87; P = 0.003; HR = 1.02; 95% CI: 0.82-1.28; P = 0.83 respectively, for the age and sex adjusted model]. Furthermore, it was related to slightly higher levels of plasma adiponectin CC 6.94, CA 7.27, AA 7.86 μg/ml, P = 0.0002] and high density lipoprotein (HDL)-cholesterol (CC 52.08, CA 53.05 and AA 55.27 mg/dl, P = 0.002), based on additive models. Adjustment for adiponectin and HDL-cholesterol did not attenuate the association between the SNP and IS risk. In contrast, adjustment for adiponectin abolished the association between the SNP and HDL-cholesterol and adjustment for HDL-cholesterol attenuated the association between the SNP and adiponectin.ConclusionsOur findings suggest that rs2943634 is associated with IS risk and with plasma levels of HDL-cholesterol and adiponectin in this German population. Further investigations are needed to confirm these results and to clarify the mechanisms underlying the association. |
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Keywords: | DIfE German Institute of Human Nutrition SNP Single nucleotide polymorphism MI Myocardial infarction IS Ischemic stroke EPIC European Prospective Investigation into Cancer and Nutrition A Adenine C Cytosine HR Hazard ratio CI Confidence interval HDL High density lipoprotein WTCCC Welcome Trust Case Control Consortium CAD Coronary artery disease CVD Cardiovascular diseases BMI Body mass index LDL Low density lipoprotein WC Waist circumference SBP Systolic blood pressure DBP Diastolic blood pressure TG Triglycerides HbA1c Glycated hemoglobin hs-CRP High-sensitivity C-reactive protein MDC Max Delbrü ck Center for Molecular Medicine HWE Hardy-Weinberg equilibrium SD Standard deviation SEM Means and standard error apoA-I Apolipoprotein A-I ABCA1 ATP-binding cassette transporter CETP Cholesteryl ester transfer protein LPL Lipoprotein lipase PI3K Phosphatidylinositol-3-kinase |
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