Megsin基因单核苷酸多态性与IgA肾病相关性研究

Association of single nucleotide polymorphism of megsin gene with IgA nephropathy

目的探讨megsin基因单核苷酸多态性（SNP）与IgA肾病的关系.方法用直接测序法广泛筛查megsin基因全部编码区、部分调控区和外显子-内含子连接区,发现11个单核苷酸多态性,挑选8个中高频SNP（频率＞0.05）,选取中国汉族散发性原发性IgA肾病患者210例,同时采用103名健康志愿者作为对照组,利用聚合酶链反应-限制型片断长度多态性（PCR-RFLP）及PCR产物直接测序法进行基因分型,对IgA肾病进行病例对照相关分析.结果外显子1中5＇非翻译区267G/A在IgA肾病发病中有显著意义：IgA肾病组中AG＋AA基因型频率为29.0%（65/210）,明显高于对照组的16.5%（17/103）,P＜0.05;等位基因A频率为14.8%（62/210）,明显高于对照组的8.7%（18/103）,P＜0.05.AG＋AA基因型与GG基因型相比,比数比为2.07,其95%可信区间为1.15～3.74.基因内部各SNP之间连锁不平衡现象非常普遍.结论megsin基因267G/A多态性与IgA肾病易感性相关,提示AG和AA基因型是IgA肾病发病的危险因素.

Objective To investigate whether the single nucleotide polymorphisms （SNPs） in the gene of megsin, a novel serine protease inhibitor, account for the pathogenicity of IgA nephropathy （IgAN）. Methods A comprehensive megsin gene survey, including the entire coding region, part of the regulatory region, and exon-intron connection region, was performed by PCR-direct sequencing on the DNA samples of peripheral blood from 12 randomly selected IgAN patients and 12 randomly selected healthy persons. Eight SNPs with moderate or high frequencies （with the frequency 〉5% ） selected from the 11 SNPs found were used as candidate SNPs. Then 210 IgAN patients proven by renal-biopsy, all of Chinese Han nationality, and 103 normal volunteers were recruited. The 8 candidate SNPs were genotyped by direct sequencing or PCR-RFLP and a case-control association study was carried out. Results The SNP of 267G/A in 5＇ untranslated region within exonl was significantly associated with IgAN. The frequency of AG/AA genotype of the IgA patients was 29.0%, significantly higher than that of the controls （ 16.5%, P〈0.05 ）. The frequency of A allele of the IgA patients was 14.8%, significantly higher than that of the controls （8.7%, P〈0.05）. The odds ratio of AG/AA genotype versus GG genotype was 2.07 with the 95% confidence interval of 1.15-3.74. The linkage disequilibrium between two SNPs existed commonly within one gene. Conclusion 267G/A in megsin gene is associated with IgAN susceptibility. AG and AA genotypes are the risk factors of pathogenesis of IgAN.