中国汉族人尿酸盐转运蛋白1基因启动子区多态性与原发性高尿酸血症的关联研究

Human urate transporter I promoter polymorphisms and hyperuricemia in Chinese Han people

目的 研究中国汉族人群人尿酸盐转运蛋白1（hURAT1）基因启动子区单核苷酸多态性（SNP）与原发性高尿酸血症的相关性。方法应用PCR扩增、基因测序方法对538名青岛及周边地区汉族人（其中原发性高尿酸血症患者215例，正常对照者323名）hURAT1基因启动子区进行序列分析。结果中国汉族人群中hURAT1基因启动子区共发现5个多态性位点，分别为-454A／T、-434T／c、-382C／T、-87C／T、＋118G／A，5个SNPs高度连锁（r。=0．99）。5个SNPs杂合突变基因型（AT、CT、CT、CT、AG）频率的分布在高尿酸血症组和正常对照组之间差异有统计学意义（均P〈0．05）。logistic回归分析显示，杂合突变基因型者（AT、CT、CT、CT、AG）发生高尿酸血症的风险较野生基因型者（AA、Tr、cc、cc、GG）降低（OR0．68～0．75）。突变型等位基因（T、C、T、T、A）携带者发生高尿酸血症的危险性比野生等位基因（A、T、C、C、G）携带者明显降低（P=0．022，P=0．038）。结论hURAT1基因启动子区-454A／T、-434T／C、-382C／T、-87C／T、＋118G／ASNPs与原发性高尿酸血症密切相关。

Objective To analyze the association of human urate transporter 1 （ hURAT1） gene promoter single-nucleotide polymorphisms（SNPs） with primary hyperuricemia（ HUA ） in Chinese Han people. Methods A total of 215 patients with HUA and 323 healthy subjects were chosen to be investigated of SNPs of hURAT1 promoter by PCR and sequencing. Results Five SNPs were identified, including-454A/T,-434T/C,-382C/T, -87C/T, and ＋ 118G/A. Pairwise linkage disequilibrium analysis displayed a high linkage disequilibrium between the five SNPs （r2 = 0. 99 ）. In HUA group, the heterozygous genotypes （AT, CT, CT, CT, AG ）frequencies were significantly lower than those in control group （ P〈0.05 ）. Logistic regression analysis showed that the heterozygosis genotypes （ AT, CT, CT, CT, AG） were protective factors of HUA （ OR 0. 68-0.75 ）. The minor allele （ T, C, T, T, A ） frequencies for both SNPswere significantly different between two groups （ P = 0. 022, P = 0. 038 ）. Conclusion These findings indicate that -454A/T,-434T/C,-382C/T,-87C/T, and ＋ 118G/A SNPs of hURAT1 gene promoter area are associated with HUA in Chinese Han population.