Department of Genetics, Texas Biomedical Research Institute San Antonio, TX, USA ; Department of Nutrition, Nutrition Research Institute, University of North Carolina at Chapel Hill Kannapolis, NC, USA.
Department of Genetics, Texas Biomedical Research Institute San Antonio, TX, USA.
Front Genet. 2013 Dec 16;4:279. doi: 10.3389/fgene.2013.00279. eCollection 2013.
Increased serum uric acid (SUA) is a risk factor for gout and renal and cardiovascular disease (CVD). The purpose of this study was to identify genetic factors that affect the variation in SUA in 632 Mexican Americans participants of the San Antonio Family Heart Study (SAFHS). A genome-wide association (GWA) analysis was performed using the Illumina Human Hap 550K single nucleotide polymorphism (SNP) microarray. We used a linear regression-based association test under an additive model of allelic effect, while accounting for non-independence among family members via a kinship variance component. All analyses were performed in the software package SOLAR. SNPs rs6832439, rs13131257, and rs737267 in solute carrier protein 2 family, member 9 (SLC2A9) were associated with SUA at genome-wide significance (p < 1.3 × 10(-7)). The minor alleles of these SNPs had frequencies of 36.2, 36.2, and 38.2%, respectively, and were associated with decreasing SUA levels. All of these SNPs were located in introns 3-7 of SLC2A9, the location of the previously reported associations in European populations. When analyzed for association with cardiovascular-renal disease risk factors, conditional on SLC2A9 SNPs strongly associated with SUA, significant associations were found for SLC2A9 SNPs with BMI, body weight, and waist circumference (p < 1.4 × 10(-3)) and suggestive associations with albumin-creatinine ratio and total antioxidant status (TAS). The SLC2A9 gene encodes an urate transporter that has considerable influence on variation in SUA. In addition to the primary association locus, suggestive evidence (p < 1.9 × 10(-6)) for joint linkage/association (JLA) was found at a previously-reported urate quantitative trait locus (Logarithm of odds score = 3.6) on 3p26.3. In summary, our GWAS extends and confirms the association of SLC2A9 with SUA for the first time in a Mexican American cohort and also shows for the first time its association with cardiovascular-renal disease risk factors.
血清尿酸（SUA）升高是痛风和肾脏及心血管疾病（CVD）的危险因素。本研究的目的是确定影响 632 名墨西哥裔美国人参与圣安东尼奥家庭心脏研究（SAFHS）中 SUA 变异的遗传因素。使用 Illumina Human Hap 550K 单核苷酸多态性（SNP）微阵列进行全基因组关联（GWA）分析。我们使用基于线性回归的关联测试，在加性等位基因效应模型下进行，同时通过亲缘关系方差分量来考虑家庭成员之间的非独立性。所有分析均在 SOLAR 软件包中进行。溶质载体家族 2 成员 9（SLC2A9）中的 rs6832439、rs13131257 和 rs737267 与 SUA 相关，达到全基因组显著性（p < 1.3×10(-7))。这些 SNP 的次要等位基因频率分别为 36.2%、36.2%和 38.2%，与 SUA 水平降低相关。所有这些 SNP 均位于 SLC2A9 的内含子 3-7 中，这是欧洲人群中先前报道的关联所在的位置。当分析与心血管-肾脏疾病危险因素的关联时，在与 SUA 强烈相关的 SLC2A9 SNP 条件下，发现 SLC2A9 SNP 与 BMI、体重和腰围显著相关（p < 1.4×10(-3))，与白蛋白-肌酐比和总抗氧化状态（TAS）呈显著相关（p < 1.4×10(-3))。SLC2A9 基因编码尿酸转运体，对 SUA 的变异性有很大影响。除了主要关联位点外，在先前报道的尿酸数量性状位点（对数比值得分= 3.6）上还发现了提示性联合连锁/关联（JLA）的证据（p < 1.9×10(-6))。3p26.3。总之，我们的 GWAS 首次在墨西哥裔美国人队列中扩展和证实了 SLC2A9 与 SUA 的关联，并首次显示了其与心血管-肾脏疾病危险因素的关联。
