CFTR基因5T位点多态性与先天性双侧输精管缺如发病风险相关性研究及meta分析

Correlation between CFTR 5T polymorphisms and the risk of congenital bilateral absence of the vas deferens

目的:探讨囊性纤维化跨膜传导调节因子(CFTR)基因5T位点多态性与先天性双侧输精管缺如(CBAVD)发病风险的相关性。方法:采用病例-对照研究方法,选取40例国内孤立发生的CBAVD患者作为病例组和104例健康男性作为对照组,用Sanger测序方法对CFTR基因9号内含子(TG)m-n(T)单倍型进行测序分型;结合本实验和Pubmed、Web of science、Medline和中国知网等数据库文献中相关数据,进行meta分析,来探讨5T突变与CBAVD发病风险的相关性。结果:Sanger测序结果表明,病例组中检测到6种基因型,分别为TG11-5T、TG12-5T、TG13-5T、TG11-7T、TG12-7T、TG11-9T;对照组中检测到7种基因型,分别为TG11-5T、TG12-5T、TG10-7T、TG11-7T、TG12-7T、TG13-7T、TG11-9T。与对照组10/208(4.81%)相比,在病例组13/80(16.25%)中观察到TG12-5T单倍型约增加了3.38倍;与对照组(0)相比,在病例组中观察到TG13-5T单倍型为6/80(7.5%);TG11-5T单倍型在对照组2/80(2.50%)和病例组4/208(1.92%)中差异很小。TG12_13-5T单倍型在病例组与对照组中差异极显著(OR=7.40,95%CI=4.83～11.34,P<0.01)。经meta分析,TG12_13-5T单倍型与男性患CBAVD疾病的相关性较高。结论:TG12_13-5T单倍型增加CBAVD患病风险,为男性生殖提供了理论基础。

Objective: To investigate the association between the 5 T site polymorphism of the cystic fibrosis transmembrane conductance regulator(CFTR) gene and the risk of congenital bilateral absence of the vas deferens(CBAVD). Methods: This case-control study included 40 male patients with isolated CBAVD in the experimental group and 104 healthy men as controls. We used the Sanger sequencing method to encode the CFTR gene intron 9(TG) m-n(T) and type the haplotypes, followed by a review and meta-analysis of the data obtained from the experiment and relevant literature from the PubMed, Web of science, Medline, CNKI and an exploration of the correlation between 5 T mutation and the risk of CBAVD. Results: Sanger sequencing revealed 6 genotypes in the CBAVD patients, including TG11-5 T, TG12-5 T, TG13-5 T, TG11-7 T, TG12-7 T and TG11-9 T, and 7 in the healthy controls, which were TG11-5 T, TG12-5 T, TG10-7 T, TG11-7 T, TG12-7 T, TG13-7 T and TG11-9 T. Compared with the controls, the CBAVD patients showed obviously increased rates of the TG12-5 T haplotype(4.81%[10/208] vs 16.25%[13/80]) and the TG13-5 T haplotype(0% vs 7.5%[6/80]), but no significant difference in the TG11-5 T haplotype(1.92%[4/208] vs 2.50%[2/80]). There was a statistically significant difference between the experimental and control groups in the TG12_13-5 T haplotype(OR = 7.40, 95% CI: 4.83-11.34, P < 0.01). The TG12_13-5 T haplotype was found to be highly correlated with CBAVD. Conclusion: The haplotype of TG12_13-5 T increases the risk of CBAVD in men, which has provided a theoretical basis for male reproduction.