hURAT1基因多态性与急性痛风性关节炎湿热证型的相关性研究

Correlation study on HURAT1 Gene Polymophism and Acute Gouty Arthritis of Damp Heat Type

目的:研究人尿酸盐阴离子蛋白1(hURAT1)基因启动子区单核苷酸多态性(SNP)与急性痛风性关节炎湿热证型的相关性。方法:临床筛选痛风性关节炎急性期发作患者110例,对照组115例。取研究对象外周抗凝血标本,通过Axygene96血基因组DNA小量制备试剂盒提取DNA,设计特异性引物,运用聚合酶链反应(PCR)进行扩增,运用基因序列测定技术,寻找SNP及突变位点。结果:hURAT1启动子区基因rs3825018基因型及等位基因频率研究显示,rs3825018杂合突变基因型(CT)、野生基因型(CC)、纯和突变基因(TT)在对照组和痛风组中的分布,分别为43.5%对27.3%,53.9%对70.0%,2.6%对2.7%,与野生基因相比,杂合突变基因型在两组中分布差异具有统计学意义(P=0.012)。其突变等位基因T基因频率为16.4%,低于对照组的24.3%(P=0.048),具有统计学差异。杂合突变基因型者患急性痛风性关节炎的风险较野生基因者降低(OR=0.493)。结论:人尿酸盐阴离子蛋白1(hURAT1)基因启动子区SNPs位点rs3825018与急性痛风性关节炎湿热证型密切相关。其突变性等位基因T为急性痛风性关节炎湿热证型的保护性等位基因。

Purpose： This research studies the correlation between SNP in hURAT1 gene promoter region and damp- heat syndrome of acute gouty arthritis. Methods： Clinical screening 110 patients had acute phase of gouty arthritis attack,115 cases of control group. Taking peripheral anticoagulant samples of research subject,extracting DNA through Axygene96 blood genomic DNA mini- prep kit,designing specific primers for amplification by PCR,is to find a SNP and mutation point by the use of gene sequencing technology. Results： The study of four SNPs genotype and allele frequencies shows that,the distribution frequency of rs3825018 heterozygous mutant genotype CT,wild genotype CC,homozygous mutation genotype TT in the control group and gout group,are：43. 5% vs. 27. 3%,53. 9% versus 70. 0%,2. 6% and 2. 7%. Comparing with the wild gene,heterozygous mutation genotype is statistically significant at the distribution difference in two groups（ P = 0. 012）. The gene frequency of SNP loci C118T mutation allele gene T is16. 4%,lower than 24. 3% of the control group. The risk for acute gouty arthritis of heterozygous mutant genotype is lower than wild genotype（ OR = 0. 493）. Conclusion： hURAT1 gene promoter region SNP loci rs3825018 correlate closely to acute gouty arthritis damp- heat syndrome. Tip mutation allele T is protective allele for damp- heat syndrome of acute gouty arthritis in hURAT1 promoter region SNPs loci rs3825018.