کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5947857 | 1172374 | 2013 | 6 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Association of SNPs in the UGT1A gene cluster with total bilirubin and mortality in the Diabetes Heart Study Association of SNPs in the UGT1A gene cluster with total bilirubin and mortality in the Diabetes Heart Study](/preview/png/5947857.png)
- UGT1A gene cluster associated with total bilirubin concentrations in the DHS.
- Bilirubin-associated SNPs were not associated vascular calcified plaque.
- Bilirubin-associated SNPs were also associated with risk for all-cause mortality.
ObjectiveA negative relationship between total bilirubin concentration (TBili) and CVD risk has been documented in a series of epidemiological studies. In addition, TBili is thought to be under strong genetic regulation via the UGT1A gene family, suggesting it may be a heritable CVD risk factor. However, few studies directly relate TBili-associated UGT1A variants to CVD severity or outcome. This study replicated the genetic association for TBili in the Diabetes Heart Study (DHS), and examined the relationships of TBili-associated SNPs with measures of subclinical CVD and mortality.MethodsThis investigation included 1220 self-described European American (EA) individuals from the DHS, a family-based study examining risk for macrovascular complications in type 2 diabetes (T2D). Genetic associations with TBili were examined using the Affymetrix Genome-wide Human SNP Array 5.0 and the Illumina Infinium Human Exome beadchip v1.0. Subsequent analyses assessed the relationships of the top TBili-associated SNPs with measures of vascular calcified plaque and mortality.ResultsA genome-wide association study detected 18 SNPs within the UGT1A gene family associated with TBili at p < 5 Ã 10â8. The top hit was rs887829 (p = 8.67 Ã 10â20). There was no compelling evidence of association between the top TBili-associated SNPs and vascular calcified plaque (p = 0.05-0.88). There was, however, evidence of association with all-cause mortality (p = 0.0004-0.06), the top hit being rs2741034.ConclusionThese findings support a potential role for UGT1A genetic variants in risk for mortality in T2D. Further quantification of the extent of CVD risk conferred by UGT1A gene family variants in a high risk cohort with T2D is still required.
Journal: Atherosclerosis - Volume 229, Issue 1, July 2013, Pages 155-160