谷胱甘肽转硫酶T1、P1和M1基因多态性与马兜铃酸肾病的关系

Association of GSTT1, GSTMI and GSTP1 gene polymorphism with aristolochic acid nephropathy

目的探讨中国人群中谷胱甘肽转硫酶T1（GSTT1）、M1（GSTM1）和P1（GSTP1）基因多态性与马兜铃酸肾病（AAN）发病的关系。方法应用多重PCR和特异性的两对引物．聚合酶链反应（CTPP—PCR）方法测定59例AAN患者（AAN组）和157例健康体检者（对照组）中GSTT1、GSTM1和GSTP1基因型，比较两组间各基因型分布及GSTP1 G等位基因频率差异。结果AAN组中GSTT1基因缺失型频率明显高于健康对照组（66．1％比48．4％，P〈0．05）。经年龄和性别校正的回归分析亦显示，GSTT1缺失的个体发生AAN的风险是携带GSTT1的个体的1．747倍（95％CI：0．818～3．731）。而GSTM1基因缺失型、GSTP1突变基因型和GSTP1 G等位基因频率在AAN组和健康对照组分别为40．7％、28．8％、16．1％和47．8％、31．8％、17．5％，差异无统计学意义。结论GSTT1基因缺失可能与AAN发病有关，是中国南方汉族人AAN的易感因素。

Objective To investigate the association of genetic polymorphisms in glutathione S-transferases T1 （GSTT1）, M1 （GSTM1） and P1 （GSTP1） with aristolochic acid nephropathy （AAN） of Chinese people in Wenzhou of China. Methods Fifty-nine patients with AAN （AAN group） including 29 male and 30 female as well as 157 healthy ethnically matched controls （control group） including 93 male and 64 female were enrolled in this study. The genotypes of GSTT1, GSTM1 and GSTP1 were determined by multiple PCR and confronting twopair primers PCR （CTPP-PCR）. Results The genotype frequencies of GSTP1 were in Hardy- Weinberg equilibrium. Compared with the healthy controls, the frequency of GSTT1 null genotype was significantly higher in the patients with AAN （66.1% vs 48.4% ,P〈0.05）. Risk of AAN for individuals with GSTT1 null genotype was 1.747 fold of those without GSTT1 null genotype （95% CI=0.818-3.731）. The frequency of GSTM1 null genotype, GSTP1 variant genotypes and GSTP1 G allele in the patients and in the controls were 40.7%, 28.8%, 16.1% and 47.8%, 31.8%, 17.5%, respectively, which were not significantly different. No significant differences were found in prevalence of GSTM1 and GSTP1 gene distribution between patients and controls. Conclusion GSTT1. gene polymorphism appears to be associated with susceptibility to AAN in Southern China.