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.
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DOI：
10.1016/j.atherosclerosis.2013.04.008
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发表时间：
2013-07
期刊：
影响因子：
5.3
通讯作者：
Bowden DW
中科院分区：
文献类型：
--
作者：
Cox AJ;Ng MC;Xu J;Langefeld CD;Koch KL;Dawson PA;Carr JJ;Freedman BI;Hsu FC;Bowden DW
一系列流行病学研究证明，总胆红素浓度(TBILI)与心血管疾病风险之间存在负相关关系。此外，TBILI被认为是通过UGT1A基因家族受到强烈的遗传调控，提示它可能是一个可遗传的CVD危险因素。然而，很少有研究直接将TBILI相关的UGT1A变异与CVD的严重程度或预后联系起来。这项研究在糖尿病心脏研究(DHS)中复制了TBILI的遗传关联，并研究了TBILI相关SNPs与亚临床心血管疾病和死亡率的关系。这项调查包括来自国土安全部的1220名自称欧洲裔美国人(EA)的人，这是一项基于家庭的研究，旨在研究2型糖尿病(T2D)大血管并发症的风险。使用Affymetrix全基因组人类SNP阵列5.0和Illumina Infinium人类外显子组珠芯片v1.0研究了与TBILI的遗传相关性。随后的分析评估了与TBILI相关的顶级SNPs与血管钙化斑块和死亡率的关系。全基因组关联研究在UGT1A基因家族中发现了18个SNPs，与tBILI相关。最高命中率为rs887829(p=8.67×10-20)。没有令人信服的证据表明，与TBILI相关的顶级SNPs与血管钙化斑块有关(p=0.05-0.88)。然而，有证据表明与全因死亡率有关(p=0.0004-0.06)，最高的死亡率是2741034卢比。这些发现支持UGT1A基因变异在T2D死亡风险中的潜在作用。在T2D高危人群中，仍需进一步量化UGT1A基因家族变异带来的心血管疾病风险程度。
A 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. This 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. A genome-wide association study (GWAS) detected 18 SNPs within the UGT1A gene family associated with TBili at p<5×10-8. The top hit was rs887829 (p=8.67×10-20). 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. These 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.
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胆红素在糖尿病，代谢综合征和心血管疾病中的作用。
影响因子：
5.6
作者：
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通讯作者：
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DOI：
10.1111/j.1464-5491.2011.03560.x
发表时间：
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期刊：
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作者：
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