Genetics of Variation in Serum Uric Acid and Cardiovascular Risk Factors in Mexican Americans
Genetics of Variation in Serum Uric Acid and Cardiovascular Risk Factors in Mexican Americans
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DOI：
10.1210/jc.2008-0682
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发表时间：
2009-02-01
影响因子：
5.8
通讯作者：
Arar, Nedal H.
中科院分区：
文献类型：
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作者：
Voruganti, V. Saroja;Nath, Subrata D.;Arar, Nedal H.
背景资料：血清尿酸升高与几种心血管疾病（CVD）风险因素相关，如高血压、炎症、内皮功能障碍、胰岛素抵抗、血脂异常和肥胖。然而，尿酸作为CVD的独立危险因素的作用尚不清楚。目的：本研究的目的是定位墨西哥裔美国人中调节血清尿酸变化的数量性状位点，并建立血清尿酸与其他CVD危险因素之间的关系（n = 848;男性= 310，女性= 538）参加了圣安东尼奥家庭心脏研究。方法：采用方差分量分解法进行定量遗传分析，在软件程序SOLAR中实现。结果：血清尿酸的平均值+/- SD为5.35 +/- 1.38 mg/dl。单因素遗传分析显示血尿酸等心血管病危险指标具有显著的遗传性（P < 0.005）。双因素分析显示，血尿酸与体重指数、腰围、腰臀比、体脂、血浆胰岛素、甘油三酯、高密度脂蛋白胆固醇、C反应蛋白、粒细胞巨噬细胞集落刺激因子显著相关（P < 0.05）。全基因组扫描检测调节血清尿酸变异的数量性状位点显示，染色体3 p26上的比值（LOD）得分的显著对数为4.72（经验LOD得分= 4.62; P < 0.00001）。一个LOD支持区间包含25个基因，其中一个有趣的候选基因是趋化因子受体2。结论：血尿酸的变异中存在显著的遗传成分，血尿酸与其他心血管危险因素之间存在多效性。（临床内分泌代谢杂志94：632-638，2009）
Background: Elevated serum uric acid is associated with several cardiovascular disease (CVD) risk factors such as hypertension, inflammation, endothelial dysfunction, insulin resistance, dyslipidemia, and obesity. However, the role of uric acid as an independent risk factor for CVD is not yet clear.Objective: The aim of the study was to localize quantitative trait loci regulating variation in serum uric acid and also establish the relationship between serum uric acid and other CVD risk factors in Mexican Americans (n = 848; men = 310, women = 538) participating in the San Antonio Family Heart Study.Methods: Quantitative genetic analysis was conducted using variance components decomposition method, implemented in the software program SOLAR.Results: Mean +/- SD of serum uric acid was 5.35 +/- 1.38 mg/dl. Univariate genetic analysis showed serum uric acid and other CVD risk markers to be significantly heritable (P < 0.005). Bivariate analysis showed significant correlation of serum uric acid with body mass index, waist circumference, waist/hip ratio, total body fat, plasma insulin, serum triglycerides, high-density lipoprotein cholesterol, C-reactive protein, and granulocyte macrophage-colony stimulating factor (P < 0.05). A genome-wide scan for detecting quantitative trait loci regulating serum uric acid variation showed a significant logarithm of odds (LOD) score of 4.72 (empirical LOD score = 4.62; P < 0.00001) on chromosome 3p26. One LOD support interval contains 25 genes, of which an interesting candidate gene is chemokine receptor 2.Summary: There is a significant genetic component in the variation in serum uric acid and evidence of pleiotropy between serum uric acid and other cardiovascular risk factors. (J Clin Endocrinol Metab 94: 632-638, 2009)