Association between SLC2A9 transporter gene variants and uric acid phenotypes in African American and white families.
Association between SLC2A9 transporter gene variants and uric acid phenotypes in African American and white families.
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非裔美国人和白人家庭中 SLC2A9 转运蛋白基因变异与尿酸表型之间的关联。
DOI：
10.1093/rheumatology/keq425
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Turner,StephenT
中科院分区：
文献类型：
--
作者：
Rule,AndrewD;deAndrade,Mariza;Matsumoto,Martha;Mosley,TomH;Kardia,Sharon;Turner,StephenT
目标。slc2a9基因变异与白人人群的血清尿酸有关，但对非裔美国人知之甚少。由于SLC2A9是一种转运体，与血清尿酸相比，基因变异可能与尿酸排泄（一种衡量肾小管运输的指标）的关系更为密切，尿酸排泄受其产生和肾外清除的影响。方法：在动脉病变遗传流行病学网络队列中获得分布在SLC2A9基因上的单核苷酸多态性（snp）的基因型。通过调整年龄、性别、利尿剂使用、BMI、同型半胱氨酸和甘油三酯，我们评估了snp与血清尿酸、尿尿酸与肌酐比值的关系。结果：我们在1155名非裔美国人（53个snp）和1132名白人（63个snp）中发现了与血清尿酸相关的slc2a9基因变异。非洲裔美国人（rs13113918）和白人受试者（rs11723439）中最具统计学意义的snp位于该基因的后半部分，分别解释了2.7和2.8%的血清尿酸变异。在对非裔美国人的SNP进行调整后，0.9%的血清尿酸变异可以用该基因前半部分的SNP （rs1568318）来解释。出乎意料的是，SLC2A9基因变异与血清尿酸的相关性强于与尿酸的部分排泄。结论：这些发现支持了SLC2A9基因变异影响非裔美国人尿酸水平的两个不同位点，并提示SLC2A9基因变异通过肾脏和肾外清除影响血清尿酸水平。
Objectives.SLC2A9gene variants associate with serum uric acid in white populations, but little is known about African American populations. Since SLC2A9 is a transporter, gene variants may be expected to associate more closely with the fractional excretion of urate, a measure of renal tubular transport, than with serum uric acid, which is influenced by production and extrarenal clearance.Methods.Genotypes of single nucleotide polymorphisms (SNPs) distributed across theSLC2A9gene were obtained in the Genetic Epidemiology Network of Arteriopathy cohorts. The associations of SNPs with serum uric acid, fractional excretion of urate and urine urate-to-creatinine ratio were assessed with adjustments for age, sex, diuretic use, BMI, homocysteine and triglycerides.Results.We identifiedSLC2A9gene variants that were associated with serum uric acid in 1155 African American subjects (53 SNPs) and 1132 white subjects (63 SNPs). The most statistically significant SNPs in African American subjects (rs13113918) and white subjects (rs11723439) were in the latter half of the gene and explained 2.7 and 2.8% of the variation in serum uric acid, respectively. After adjustment for this SNP in African Americans, 0.9% of the variation in serum uric acid was explained by an SNP (rs1568318) in the first half of the gene. Unexpectedly,SLC2A9gene variants had stronger associations with serum uric acid than with fractional excretion of urate.Conclusions.These findings support two different loci by which SLC2A9 variants affect uric acid levels in African Americans and suggest SLC2A9 variants affect serum uric acid level via renal and extrarenal clearance.
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影响因子：
13.6
作者：
Weiner, Daniel E.;Tighiouart, Hocine;Levey, Andrew S.
通讯作者：
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作者：
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