Dataset Information

Association of a 62 Variants Type 2 Diabetes Genetic Risk Score With Markers of Subclinical Atherosclerosis: A Transethnic, Multicenter Study.

ABSTRACT: Type 2 diabetes mellitus (T2D) and cardiovascular disease share risk factors and subclinical atherosclerosis (SCA) predicts events in those with and without diabetes mellitus. T2D genetic risk may predict both T2D and SCA. We hypothesized that greater T2D genetic risk is associated with higher extent of SCA.In a cross-sectional analysis, including ?9210 European Americans, 3773 African Americans, 1446 Hispanic Americans, and 773 Chinese Americans without known cardiovascular disease and enrolled in the Framingham Heart Study, Coronary Artery Risk Development in Young Adults, Multi-Ethnic Study of Atherosclerosis, and Genetic Epidemiology Network of Arteriopathy studies, we tested a 62 T2D-loci genetic risk score for association with measures of SCA, including coronary artery or abdominal aortic calcium score, common and internal carotid artery intima-media thickness, and ankle-brachial index. We used ancestry-stratified linear regression models, with random effects accounting for family relatedness when appropriate, applying a genetic-only (adjusted for sex) and a full SCA risk factors-adjusted model (significance, P<0.01=0.05/5, number of traits analyzed). An inverse association with coronary artery calcium score in Multi-Ethnic Study of Atherosclerosis Europeans (fully-adjusted P=0.004) and with common carotid artery intima-media thickness in the Framingham Heart Study (P=0.009) was not confirmed in other study cohorts, either separately or in meta-analysis. Secondary analyses showed no consistent associations with ?-cell and insulin resistance genetic risk sub-scores in the Framingham Heart Study and in the Coronary Artery Risk Development in Young Adults.SCA does not have a major genetic component linked to a burden of 62 T2D loci identified by large genome-wide association studies. A shared T2D-SCA genetic basis, if any, might become apparent from better functional information about both T2D and cardiovascular disease risk loci.

SUBMITTER: Dauriz M

PROVIDER: S-EPMC4472563 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Association of a 62 Variants Type 2 Diabetes Genetic Risk Score With Markers of Subclinical Atherosclerosis: A Transethnic, Multicenter Study.

Dauriz Marco M Porneala Bianca C BC Guo Xiuqing X Bielak Lawrence F LF Peyser Patricia A PA Durant Nefertiti H NH Carnethon Mercedes R MR Bonadonna Riccardo C RC Bonora Enzo E Bowden Donald W DW Florez Jose C JC Fornage Myriam M Hivert Marie-France MF Jacobs David R DR Kabagambe Edmond K EK Lewis Cora E CE Murabito Joanne M JM Rasmussen-Torvik Laura J LJ Rich Stephen S SS Vassy Jason L JL Yao Jie J Carr Jeffrey J JJ Kardia Sharon L R SL Siscovick David D O'Donnell Christopher J CJ Rotter Jerome I JI Dupuis Josée J Meigs James B JB

Circulation. Cardiovascular genetics 20150324 3

<h4>Background</h4>Type 2 diabetes mellitus (T2D) and cardiovascular disease share risk factors and subclinical atherosclerosis (SCA) predicts events in those with and without diabetes mellitus. T2D genetic risk may predict both T2D and SCA. We hypothesized that greater T2D genetic risk is associated with higher extent of SCA.<h4>Methods and results</h4>In a cross-sectional analysis, including ≤9210 European Americans, 3773 African Americans, 1446 Hispanic Americans, and 773 Chinese Americans wi ...[more]

PMID: 25805414

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Project description:Gestational diabetes mellitus (GDM) can be considered a silent risk for out-of-pregnancy diabetes mellitus (DM) and cardiovascular disease (CVD) later in life. We aimed to assess the predictive role of 3rd trimester lipid profile during pregnancy for the susceptibility to markers of subclinical atherosclerosis (CVD susceptibility) at 3 years in a cohort of women with history of GDM. A secondary aim is to evaluate the usefulness of novel nutrigenetic markers, in addition to traditional parameters, for predicting early subclinical atherosclerosis in such women in order to plan adequate early prevention interventions. We assessed 28 consecutive GDM women in whom we collected socio-demographic characteristics and clinical and anthropometric parameters at the 3rd trimester of pregnancy. In a single blood sample, from each patient, we assessed 9 single nucleotide polymorphisms (SNPs) from 9 genes related to nutrients and metabolism, which were genotyped by High Resolution Melting analysis. All women then attended a 3-year-postpartum follow-up and on that occasion performed an oral glucose tolerance test (OGTT, with 75?g oral glucose), the measurement of carotid artery intima-media thickness (cIMT), and analyses of metabolic parameters. In addition, we evaluated the physical activity level and the adherence to Mediterranean diet (MedDiet) using the International Physical Activity Questionnaire (IPAQ-short version) and PREDIMED questionnaires. We found an association between 3rd trimester triglycerides and cIMT (p = 0.014). We also found significant associations between the APOA5 CC genotype and cIMT after adjustments for age and body mass index (p = 0.045) and between the interaction CC APOA5/CC LDLR and cIMT (p = 0.010). At the follow-up, the cohort also featured a mean BMI in the overweight range and a high mean waist circumference. We found no difference in the MedDiet adherence, physical activity, and smoking but an inverse correlation between the PREDIMED and the IPAQ scores with the IMT. In conclusion, this preliminary study provides insight into the predictive role of lipid profile during pregnancy and of some genetic variants on cIMT taken as a parameter of subclinical CVD susceptibility in GDM.

Dataset Information

Association of a 62 Variants Type 2 Diabetes Genetic Risk Score With Markers of Subclinical Atherosclerosis: A Transethnic, Multicenter Study.

Publications

Association of a 62 Variants Type 2 Diabetes Genetic Risk Score With Markers of Subclinical Atherosclerosis: A Transethnic, Multicenter Study.

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