沉默信息调节因子1基因多态性与广西人群显微镜下多血管炎的病例对照研究

SIRT1 gene polymorphism and microscopic polyangiitis in Guangxi population:A case-control study

目的 探讨沉默信息调节因子(SIRT1)遗传变异(rs1467568、rs4746720)与广西人群显微镜下多血管炎(microscopic polyangiitis,MPA)的相关性。方法 利用多重聚合酶链反应(PCR)结合高通量测序法对208例MPA患者和211例健康志愿者的SIRT1多态性进行基因分型;比较等位基因频率和基因型分布差异,进行连锁不平衡、单体型以及遗传模型的分层分析;评价不同基因型与临床症状的发生、实验室生化指标的关系。结果 SIRT1 rs1467568、rs4746720的基因型、等位基因频率以及单体型在两组之间的差异均无统计学意义(P> 0.05)。在年龄≥54岁亚组中,SIRT1 rs1467568的显性模型(OR=0.50,95%CI:0.27~0.92,P=0.026)、超显性模型(OR=0.49,95%CI:0.26~0.92,P=0.026)和加性模型(OR=0.57,95%CI:0.33~0.99,P=0.045)与MPA较低易感性相关。在rs1467568中,携带GG基因型的MPA患者具有更高水平的谷丙转氨酶(P=0.012);在rs4746720中,携带TT、TC基因型的MPA患者具有更高水平的谷草转氨酶(P=0.036)。结论 SIRT1 rs4746720与广西人群MPA易感性无关,而rs1467568可能与广西部分人群(≥54岁)MPA易感性相关;rs1467568、rs4746720分别与MPA患者丙氨酸氨基转移酶、天门冬氨酸氨基转移酶水平存在关联。

Objective To explore the relationship between SIRT1 genetic variation(rs1467568,rs4746720) and microscopic polyangiitis(MPA) in Guangxi population.Methods The SIRT1 polymorphisms of 208 patients with microscopic polyangiitis(MPA) and 211 healthy volunteers were genotyped by multiplex polymerase chain reaction(PCR) and high throughput sequencing.The allele frequencies and genotypes were compared.The linkage disequilibrium,haplotype and genetic model were analyzed.The relationship between different genotypes and clinical symptoms and laboratory biochemical indexes was evaluated.Results The results showed no significant difference between the two groups in genotype,allele frequency,and haplotype of SIRT1 rs1467568and rs4746720(P>0.05).In the age group ≥ 54 years old,the dominant model(OR = 0.50,95%CI:0.27 ~ 0.92,P = 0.026),overdominant model(OR = 0.49,95%CI:0.26 ~ 0.92,P = 0.026) and additive model(OR = 0.57,95%CI:0.33 ~ 0.99,P = 0.045) of SIRT1 rs1467568 were associated with lower susceptibility to MPA.In rs1467568,MPA patients with GG genotype had higher levels of glutamic pyruvic transaminase(P = 0.012),while in rs4746720,MPA patients with TT and TC genotypes had higher levels of glutamic oxaloacetic transaminase(P = 0.036).Conclusions In this study,SIRT1 rs4746720 was not related to the susceptibility to MPA in Guangxi population,but rs1467568 may be associated with the susceptibility to MPA in some people (≥ 54 years old) in Guangxi,and rs1467568 and rs4746720 were associated with the levels of glutamic pyruvic transaminase and glutamic oxaloacetic transaminase in patients with MPA.