亚甲基四氢叶酸还原酶C677T基因多态性与特发性男性不育症相关性分析

Association between methyltetrahydrofolate reductase c677t gene polymorphism and idiopathic male infertility

目的研究亚甲基四氢叶酸还原酶(MTHFR)C677T基因多态性与精液参数相关性,并分析MTHFR C677T基因多态性分布与特发性男性不育症的易感性。方法收集我院2017年4月至2018年9月就诊的特发性男性不育症患者167例,根据WHO《人类精液检查与处理实验室检查手册》第五版要求行精液质量分析;精液质量参数包括:精液体积、精子密度、精子总数、前向运动精子率、畸形率和液化率。根据实时荧光定量聚合酶链式反应(RT-PCR)检测MTHFR C677T基因多态性,探讨MTHFR C677T基因多态性与精液质量的相关性。为进一步明确MTHFR C677T与男性特发性不育症之间的关系,同期收集65例正常生育男性组成对照组,分析MTHFR C677T多态性位点在不育组和对照组中的分布及其与特发性不育症之间的易感性。结果特发性不育症患者组中,与野生基因型(CC)相比,携带突变杂合子(CT)和突变纯合子(TT)基因型患者的前向精子运动率均降低,差异具有显著性(P<0.01,P<0.05);精液量、精子密度、精子总数、畸形率和液化率在各基因型间比较差异无统计学意义(P>0.05)。特发性不育症患者组TT基因型占26.3%,T等位基因频率为47.6%,分别高于对照组的10.7%和32.3%(P<0.05,P<0.01);Logistic回归分析显示,携带TT基因型的男性发生特发性不育症的危险性是CC型的3.626倍(95%CI:1.452-9.058);按照精液质量检测指标进一步对167例男性特发性不育症患者进行分组,发现携带TT基因型的男性发生弱精子症、畸精子症和弱畸精子症的风险升高,其OR值分别为3.536、4.138和4.082(95%CI:1.377-9.097;95%CI:1.564-10.947;95%CI:1.464-11.383);而携带CT基因型的男性发生弱畸精子症的危险性是CC基因型的2.143倍(95%CI:1.028-4.467)。少精子症、少畸精子症、少弱精子症和少弱畸精子症与MTHFR C667T基因型分布无关(P>0.05)。结论 MTHFR C677T多态性与前向精子运动率有关,TT基因型可能是男性患特发性不育症的易感基因。

Objective:To study the association between methylenetetrahy-drofolate reductase(MTHFR)C677T gene polymorphism and semen parameters.The distribution of MTHFR C677T gene polymorphism and susceptibility of idiopathic male infertility were analyzed.Methods:167 cases of idiopathic male infertility from April 2017 to September 2018 were collected and analyzed according to the fifth edition of the Manual for Laboratory examination of Human semen examination and processing.The semen quality parameters include:volume of semen,Sperm density,total sperm count,sperm forward motility rate,deformity rate and liquefaction rate.The polymorphism of MTHFR C677T gene was detected by real-time fluorescence quantitative polymerase chain reaction(RT-PCR),and the relationship between the polymorphism of MTHFR C677T gene and semen quality was investigated.In order to further clarify the relationship between MTHFR C677T and male idiopathic infertility,65 normal fertile men were collected as control group.Results:In the idiopathic male infertility group,sperm forward motility rate of the patients with CT and TT genotype was significantly lower than that of the men with CC genotype(P<0.01,P<0.05).There was no significant difference in the sperm volume,sperm density,total sperm count,deformity rate,and liquefaction rate.However,TT genotype was 26.3%and T allele frequency was 47.6%in idiopathic infertility group,which was higher than that in control group(10.7%and 32.3%,P<0.05,P<0.01);The risk of idiopathic infertility in men with TT genotype was3.626 times higher than that of CC type(95%CI:1.452-9.058).It was also found that the risk of asthenospermia,teratospermia and asthenoteratospermia was increased with TT genotype,with the odds ratio(OR)values of 3.536,4.138 and 4.082(95%CI:1.377-9.097;95%CI:1.564-10.947;95%CI:1.464-11.383).Men with CT genotype were 2.143 times more likely to develop asthenoteratospermia than those with CC genotype(95%CI:1.028-4.467).Oligospermia,oligoasthenospermia,oligoteratospermia and oligoasthenoteratospermia were not correlated with the genotype distribution of MTHFR C677T(P>0.05).Conclusion:MTHFR C677T polymorphism is associated with sperm forward motility rate.TT genotype may be a susceptible gene for idiopathic infertility in men.