人类白细胞抗原-DQA1、细胞色素P4503A5*3基因多态性与特发性膜性肾病遗传易感性关联性研究

Correlation between gene polymorphisms of HLA-DQA1 and CYP3A5*3 and genetic susceptibility of idiopathic membranous nephropathy

目的:探讨分析人类白细胞抗原(HLA)-DQA1、细胞色素P450(CYP)3A5*3基因多态性与特发性膜性肾病(IMN)遗传易感性的关联性。方法:将IMN患者62例作为研究组,另将健康者62例作为对照组。采用聚合酶链反应(PCR)技术和基因测序技术检测入组患者的HLA-DQA1(rs2187668)、CYP3A5*3(rs776746)基因型,判断各基因型与IMN患者的关系。结果:研究组中HLA-DQA1 rs2187668基因型AA占比高于对照组(P<0.05),基因型GG、AG占比低于对照组(均P<0.05);研究组等位基因A占比高于对照组(P<0.05)。研究组与对照组CYP3A5*3 rs776746不同基因型占比及等位基因占比比较无统计学差异(均P>0.05)。HLA-DQA1 rs2187668AA基因型IMN患者24 h尿蛋白量和血肌酐水平显著高于AG和GG型,肾小球滤过率显著低于AG和GG型(均P<0.05)。结论:HLA-DQA1 rs2187668位点的基因多态性与IMN的发生有关,AA基因型和等位基因A可增加IMN易感性。

Objective:To explore the correlation between gene polymorphisms of human leukocyte antigen(HLA)-DQA1 and cytochrome P450(CYP)3A5*3 and genetic susceptibility of idiopathic membranous nephropathy(IMN).Methods:A total of 62 patients with IMN and 62 healthy controls as study group and control group,respectively.The genotypes of HLA-DQA1(rs2187668)and CYP3A5*3(rs776746)were detected by polymerase chain reaction(PCR)and gene sequencing method,and their relationship with IMN was determined.Results:The proportion of HLA-DQA1 rs2187668 genotype AA in study group was higher than that in control group(P<0.05),and the proportion of GG and AG genotype was lower than that in the control group(all P<0.05).The proportion of allele A in study group was higher than that in control group(P<0.05).There was no significant difference in the proportions of different genotypes and alleles in CYP3A5*3(rs776746)between the two groups(all P>0.05).The levels of 24-hour urinary protein and serum creatinine in IMN patients with HLA-DQA1(rs2187668)’s genotype AA were significantly higher than those with genotypes AG and GG,and glomerular filtration rate was significantly lower than that with genotypes AG and GG(all P<0.05).Conclusion:The polymorphisms of HLA-DQA1 gene at rs2187668 locus are related to the occurrence of IMN,genotype AA and allele A will increase IMN susceptibility.