BCAS3基因rs11653176位点单核苷酸多态性与痛风的相关性研究

Association of BCAS3 rs11653176 gene polymorphism with the occurrence of gout

目的探讨原发性痛风易感基因（BCAS3）rs11653176位点单核苷酸多态性与山东沿海地区汉族男性痛风发病之间的相关性。方法选取痛风组缓解期患者152例、急性期68例、健康对照者280例、单纯性高尿酸血症患者252例，均为男性。TaqMan探针技术对BCAS3基因rs11653176位点进行基因分型：RT—qPCR测定各例PBMC中BCAS3基因mRNA的表达水平；ELISA法检测痛风患者和对照者血清中肿瘤坏死因子α（TNF-α）、白细胞介素（IL）-6和IL-18的水平。结果BCAS3基因rs11653176位点等位基因频率的改变与痛风存在相关性（P〈0．01）；痛风患者BCAS3mRNA水平显著高于健康人和高尿酸血症患者（P〈0．01）；痛风患者中，含C等位基因的基因型BCAS3mRNA表达水平高于含T等位基因的基因型（P〈0．05）;痛风急性期炎症因子水平明显高于缓解期和高尿酸血症患者（P〈0．01）。结论BCAS3基因rs11653176位点等位基因频率的改变（高C低T），可能促进该基因高表达，导致痛风的发生。而痛风患者发作与炎症因子的产生密切相关。

Objective To explore the relationship between the polymorphisms of the primary gout predisposing gene （BCAS3） rs11653176 locus and the incidence of gout in Han Chinese men in coastal areas of Shandong Province. Methods One hundred and fifty-two cases of patients with gout remission, 68 cases of acute stage, 252 patients with hyperuricemia, and 280 healthy subjects, total males, were enrolled. Genotyping the rs11653176 locus of BCAS3 gene by TaqMan probe technique. The expression level of BCAS3 gene mRNA in each PBMC was measured by RT-qPCR. The levels of tumor necrosis factor-α （ TNF-α）, interleukin-6 （ IL-6 ） , and interleukin-18 （IL-18） in serum were measured by ELISA. Results The change of allele frequency of rs11653176 locus in BCAS3 gene was associated with gout（ P〈0.01 ）. BCAS3 mRNA in patients with gout was significantly higher than that of healthy people and patients with hyperuricemia （P〈0.01）. In gout patients, the expression level of BCAS3 gene containing C allele was higher than that of T allele （ mRNA, P〈0.05 ）. The inflammatory factors in the acute phase of gout were significantly higher than those in phases of remission and hyperuricemia （ P 〈 0.01 ）. Conclusion Changes in the allele frequency of BCAS3 alleles rs11653176 （ high C, low T） may contribute to the expression of this gene, and lead to gout. And the onset of gout is closely related to the production of inflammatory factors.