CTLA4基因多态性与不明原因习惯性流产发生风险关系

Relationship between CTLA4 gene polymorphism and risk of unexplained habitual abortion occurance

目的:探究细胞毒性T淋巴细胞相关性抗原-4(CTLA4)与不明原因习惯性流产(UHA)发生风险关系。方法:选取本院治疗的98例UHA患者,另选107例正常妊娠者为对照组,提取血液DNA,聚合酶链式反应-限制性片段多态性法检测CTLA-4基因rs5742909、rs4553808、rs231775位点基因分型,酶联免疫吸附法检测血清Th1型、Th2型细胞因子表达;分析CTLA4基因型与UHA发生风险、各位点基因型与炎症因子水平关系。结果:与对照组相比,UHA组血清干扰素γ(IFN-γ)、肿瘤坏死因子-α(TNF-α)、白介素-2(IL-2)水平均升高,IL-4、IL-6、IL-10水平均降低(P<0.05)。两组CTLA4基因rs5742909、rs4553808、rs231775位点实际基因频率与理论值无差异(P>0.05),符合Hardy-Weinberg遗传平衡定律;s5742909位点T等位基因频率、rs231775位点G等位基因频率均高于对照组(P<0.05)。rs5742909、rs231775不同基因型者血清IFN-γ、TNF-α、IL-2、IL-4、IL-6、IL-10水平有差异(P<0.05)。logistic多因素回归分析显示rs5742909 T等位基因携带者发生UHA相对危险度为C等位基因的1.984倍,rs231775 T等位基因携带者发生UHA相对危险度为C等位基因的1.837倍。结论:CTLA4基因rs5742909、rs231775位点多态性与UHA发生相关,rs5742909位点C→T突变、rs231775位点A→G突变可增加UHA的发病风险。

Objective:To explore the relationship between cytotoxic T lymphocyte associated antigen-4(CTLA4)of women and their risk of unexplained habitual abortion(UHA)occurance.Methods:98 women with UHA were selected in study group,and another 107 normal pregnant women were selected in control group.Serum of the women in the two groups was collected and their DNA from cell blood was extracted.Polymerase chain reaction-restriction fragment polymorphism(PCR-RFLP)was used to detect the genotypes of CTLA-4 gene rs5742909 loci,rs4553808 loci and rs231775 loci.The expressions of serum Th1 and Th2 cytokines levels were detected by ELISA.The relationship between CTLA4 genotype and the risk of UHA,and the relationship between genotypes and inflammatory factor level were analyzed.Results:The levels of serum interferon-γ(IFN-γ),tumor necrosis factor-ɑ(TNF-ɑ),and interleukin-2(IL-2)of women in the study group were significant higher than those of women in the control group,while the levels of IL-4,IL-6,and IL-10 of women in the study group were significant lower(P<0.05).The frequency value of actual gene rs5742909 loci and rs231775 loci of CTLA4 gene of women in the study group had no significant different from their theoretical frequency value(P>0.05),which conformed to Hardy-Weinberg's law of genetic balance.The T allele frequency of s5742909 loci and the G allele frequency of rs231775 loci of women in the study group were significant higher than those of women in the control group(P<0.05).The levels of serum IFN-γ,TNF-ɑ,IL-2,IL-4,IL-6,and IL-10 of women with rs5742909 and rs231775 genotypes had significant different(P<0.05).Logistic multivariate regression analysis showed that the relative risk of women carried rs5742909 T allele was 1.984 times higher than that of UHA women carried C allele,and the relative risk of women carried rs231775 T allele was 1.837 times higher than that of UHA women carried C allele.Conclusion:The polymorphisms of rs5742909 and rs231775 loci of CTLA4 gene are associated with UHA occurance,and C→T mutation at rs5742909 loci and A→G mutation at rs231775 loci can increase the risk of UHA occurance.