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Polymorphisms in the Selenoprotein S gene and subclinical cardiovascular disease in the Diabetes Heart Study.

ABSTRACT: Selenoprotein S (SelS) has previously been associated with a range of inflammatory markers, particularly in the context of cardiovascular disease (CVD). The aim of this study was to examine the role of SELS genetic variants in risk for subclinical CVD and mortality in individuals with type 2 diabetes mellitus (T2DM). The association between 10 polymorphisms tagging SELS and coronary (CAC), carotid (CarCP) and abdominal aortic calcified plaque, carotid intima media thickness and other known CVD risk factors was examined in 1220 European Americans from the family-based Diabetes Heart Study. The strongest evidence of association for SELS SNPs was observed for CarCP; rs28665122 (5' region; ? = 0.329, p = 0.044), rs4965814 (intron 5; ? = 0.329, p = 0.036), rs28628459 (3' region; ? = 0.331, p = 0.039) and rs7178239 (downstream; ? = 0.375, p = 0.016) were all associated. In addition, rs12917258 (intron 5) was associated with CAC (? = -0.230, p = 0.032), and rs4965814, rs28628459 and rs9806366 were all associated with self-reported history of prior CVD (p = 0.020-0.043). These results suggest a potential role for the SELS region in the development subclinical CVD in this sample enriched for T2DM. Further understanding the mechanisms underpinning these relationships may prove important in predicting and managing CVD complications in T2DM.

SUBMITTER: Cox AJ

PROVIDER: S-EPMC3597768 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Polymorphisms in the Selenoprotein S gene and subclinical cardiovascular disease in the Diabetes Heart Study.

Cox Amanda J AJ Lehtinen Allison B AB Xu Jianzhao J Langefeld Carl D CD Freedman Barry I BI Carr J Jeffrey JJ Bowden Donald W DW

Acta diabetologica 20121116 3

Selenoprotein S (SelS) has previously been associated with a range of inflammatory markers, particularly in the context of cardiovascular disease (CVD). The aim of this study was to examine the role of SELS genetic variants in risk for subclinical CVD and mortality in individuals with type 2 diabetes mellitus (T2DM). The association between 10 polymorphisms tagging SELS and coronary (CAC), carotid (CarCP) and abdominal aortic calcified plaque, carotid intima media thickness and other known CVD r ...[more]

PMID: 23161441

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Project description:Background and objectivesBlacks have high rates of cardiovascular disease and mortality. Diabetes and CKD, risk factors for cardiovascular mortality in the general population, are common among blacks. We sought to assess their contribution to cardiovascular disease and mortality in blacks.Design, setting, participants, & measurementsThis observational cohort study was of 3211 participants in the Jackson Heart Study (enrolled 2000-2004). Rates of incident stroke, incident coronary heart disease, and cardiovascular mortality were quantified in participants with diabetes, CKD (eGFR<60 ml/min per 1.73 m(2), urine albumin-to-creatinine ratio ≥30 mg/g, or both), or both through 2012, with a median follow-up of 6.99 years.ResultsFour hundred fifty-six (14.2%) participants had only diabetes, 257 (8.0%) had only CKD, 201 (6.3%) had both, and 2297 (71.5%) had neither. Diabetes without CKD was associated with excess risks of incident stroke, incident coronary heart disease, and cardiovascular mortality after adjustment for demographic and clinical covariates, including prevalent cardiovascular disease (excess incidence rates, 2.6; 95% confidence interval, 0.5 to 4.7; 2.6; 95% confidence interval, 0.3 to 4.8; and 2.4; 95% confidence interval, 0.4 to 4.3 per 1000 person-years, respectively). CKD without diabetes was associated with comparable nonsignificant excess risks for incident stroke and coronary heart disease (2.5; 95% confidence interval, -0.1 to 5.2 and 2.4; 95% confidence interval, -0.8 to 5.5 per 1000 person-years, respectively) but a larger excess risk for cardiovascular mortality (7.3; 95% confidence interval, 3.0 to 11.5 per 1000 person-years). Diabetes and CKD together were associated with greater excess risks for incident stroke (13.8; 95% confidence interval, 5.3 to 22.3 per 1000 person-years), coronary heart disease (12.8; 95% confidence interval, 4.9 to 20.8 per 1000 person-years), and cardiovascular mortality (14.8; 95% confidence interval, 7.2 to 22.3 per 1000 person-years). The excess risks associated with the combination of diabetes and CKD were larger than those associated with established risk factors, including prevalent cardiovascular disease.ConclusionsThe combination of diabetes and kidney disease is associated with substantial excess risks of cardiovascular events and mortality among blacks.

Dataset Information

Polymorphisms in the Selenoprotein S gene and subclinical cardiovascular disease in the Diabetes Heart Study.

Publications

Polymorphisms in the Selenoprotein S gene and subclinical cardiovascular disease in the Diabetes Heart Study.

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