MTHFR、MTRR基因多态性与精子DNA完整性的相关性分析  

A correlation analysis between MTHFR and MTRR gene polymorphism and sperm DNA fragmentation index

作　　者：刘春辉 陕文生[1] 王志强[1] 朱晨[1] 王海 李少君 王连[3] 彭靖[4] Liu ChunHui;Shan WenSheng;Wang ZhiQiang;Zhu Chen;Wang Hai;Li ShaoJun;Wang Lian;Peng Jing(Department of Andrology,Gansu Provincial Maternity and Child-care Hospital;Department of Reproductive Medicine and Urology,Gansu Provincial Maternity and Child-care Hospital;Genetic Medicine Center,Gansu Provincial Maternity and Child-care Hospital;Andrology Center,Peking University First Hospital)

机构地区：[1]甘肃省妇幼保健院男科 [2]甘肃省妇幼保健院生殖泌尿科 [3]甘肃省妇幼保健院医学遗传中心 [4]北京大学第一医院男科中心

出　　处：《中国男科学杂志》2023年第2期62-69,共8页Chinese Journal of Andrology

基　　金：兰州市科技发展指导性计划项目(2020-ZD-4);甘肃省自然科学基金项目(20JR10RA425)。

摘　　要：目的探讨5,10-亚甲基四氢叶酸还原酶(MTHFR)、甲硫氨酸合成酶还原酶(MTRR)基因多态性与精子DNA完整性是否存在相关性。方法随机选取2017年3月至2020年12月期间在我院就诊的患者822人,分为少精子症组(A组)、弱精子症组(B组)、少弱精子症组(C组)、正常对照组(X组)。对所有入组对象进行精液分析、精子DNA碎片指数(DFI)和血浆同型半胱氨酸(HCY)、精浆HCY水平的检测、并检测他们的MTHFR C667T、MTHFR A1298C、MTRR A66G基因。所有观察对象给予叶酸片(800μg/日)、维生素B12(25μg/日)干预3个月后,再次检测精液质量与HCY。结果A、B、C、X组MTHFR C677T、MTHFR A1298C、MTRR A66G多态性发生率分别为39.1%~50.6%、39.1%~57.3%、24.7%~37.9%、10.8%~26.9%;精子参数异常的各组,MTHFR、MTRR基因多态性发生率均高于正常对照组,且均具有统计学差异。A、B、C、X组DFI值变化(药物干预前/干预后)分别为19.80±11.893/13.79±5.450,18.45±9.243/12.92±4.499,13.40±7.732/9.63±3.468,13.73±5.678/10.89±3.047,A、B、C组DFI均值均高于X组,存在显著差异,药物干预后DFI在A、B、C组出现了显著降低,存在统计学意义,在X组降低无统计学差异。血浆HCY、精浆HCY与DFI的皮尔逊相关系数分别为药物干预前r=0.902、r=0.881,干预后r=0.862、r=0.821均存在正性相关,且均具有统计学差异。结论MTHFR、MTRR多态性是导致叶酸代谢障碍的重要因素,而叶酸代谢障碍会导致HCY在人体内堆积,高HCY对精子DNA完整性会造成一定损害,两者间存在正性相关性。在给予叶酸及维生素B12干预3月后,HCY水平降低,DFI显著改善。Objective To explore the correlation between 5,10-methylenetetrahydrofolate reductase(MTHFR),methionine synthase reductase(MTRR)gene polymorphisms and sperm DNA integrity.Methods Total of 822 patients in our hospital from March 2017 to December 2020 were randomly enrolled and divided into four groups including oligozoospermia group(group A),asthenospermia group(group B),oligozoospermia group(Group C)and normal control group(Group X).Semen quality,sperm DNA fragment index(DFI),plasma homocysteine(Hcy)and seminal plasma Hcy levels were analyzed,and their MTHFR C667T,MTHFR A1298C and MTRR A66G genes were detected.All the subjects were further given with folic acid tablets(800μg/day),vitamin B12(25μg/day)for 3 months,and their DFI,plasma Hcy and seminal plasma Hcy levels were analyzed again.Results The incidence(%)of MTHFR C677T,MTHFR A1298C and MTRR A66G polymorphisms in groups A,B,C and X were 39.1~50.6,39.1~57.3,24.7~37.9 and 10.8~26.9,respectively;The incidences of MTHFR and MTRR gene polymorphisms in the groups with abnormal sperm parameters were all higher than that in the normal control group,and there were significant differences.The changes of DFI value(%)in groups A,B,C and X(before/after drug intervention)were 19.80±11.893/13.79±5.450,18.45±9.243/12.92±4.499,13.40±7.732/9.63±3.468,13.73±5.678/10.89±3.047 respectively.The mean value of DFI in group A,B and C was higher than that in group X,and there was a significant statistical difference.After drug intervention,DFI was decreased significantly in group A,B and C,however,there was no significant difference in group X.The Pearson correlation coefficients between plasma HCY,seminal plasma HCY and DFI were r=0.902 and r=0.881 before drug intervention and r=0.862 and r=0.821 after intervention,respectively.Conclusion MTHFR and MTRR polymorphisms are important factors in the occurrence of folate metabolism disorder.They often result in the accumulation of HCY in human body.High HCY level frequently damages the integrity of sperm DNA,and there is a posi

关 键 词：5 10-亚甲基四氢叶酸还原酶 甲硫氨酸合成酶还原酶 精子 DNA碎片裂 高半胱氨酸 

分 类 号：R349.6[医药卫生—基础医学] R321.1