mtND4基因突变与弱精子症精子的相关分析  

Mutation analysis of the mtND4 gene associated with asthenospermia patients

作　　者：李传连[1] 郑九嘉[1] 杨宗[1] 黄学锋[2] 方可欣[1] 楼哲丰[1] 吴永根[2] 金龙金[1] 

机构地区：[1]温州医学院生命科学学院浙江省医学遗传学重点实验室,325035 [2]温州医学院附属第一医院生殖医学中心

出　　处：《中华泌尿外科杂志》2011年第1期62-66,共5页Chinese Journal of Urology

基　　金：基金项目：浙江省自然科学基金（Y206582）;温州市科技合作项目（H20090063）

摘　　要：目的分析弱精子症精子mtND4基因突变与弱精于症的相关性，探索弱精子症的分子病因。方法按WHO标准收集56例弱精子症精液标本和44例精子活力正常精液标本，用3对引物PCR扩增mtND4基因，纯化测序，分析mtND4基因突变，比较2组标本mtND4基因突变及多重单核苷酸多态性（SNP）的差异。结果发现31个同义突变位点和12个错义突变位点，其中6个核苷酸变异位点未报道过，分别为A11026G、C11215T、A11488G、C11713T、C12908T、T10908C。对照组mtND4基因T10873C和T11944C变异率分别为61．4％（27／44）和11．4％（5／44），显著高于弱精子症组的39．3％（22／56）和0％（P〈0．05）；除T10873C和TI1944C变异外，错义突变分析发现，对照组10例中与T10873C或T11944C组成多重SNP8例，而弱精子症组10例标本中仅2例，2组间比较差异有统计学意义（P〈0．05）；上述20例错义突变标本分成多重SNP组（与T10873C或T11944C）和非多重SNP组，多重SNP组a级精子百分率和a＋b级精子百分率均显著高于非多重SNP组（P〈0．05）。结论mtND4基因错义突变可能影响精于活动力，T10873C和T11944C多态性变异对精子活动力可能是一个有益因子，两者同时存在组成多重SNP时，两者的作用可能具有相互抵消的效应。Objective To investigate the relationship between mtND4 point mutation in sperms and asthenospermia. Methods Fifty-six asthenospermia cases and 44 control cases were collected using the WHO criterion for defining asthenospermia, the regions of mtND4 gene were amplified by using PCR of 3 pairs primers. Consequently, the point mutation, missense mutation and multiple sin gle nucleotide polymorphisms （SNP） were analyzed by employing sequencing technology and bioinfor- matics tools. Results Six mutations never before identified were found. The frequency of single point mutation T10873C and Tl1944C in the control group were significantly higher than those in the asthenospermia group （P〈0.05）. Eight cases involved T10873C or Tl1944C among the 10 cases in control groups with missense mutations were found. But, there were only 2 cases with such mutation in the 10 asthenospermia cases with missense mutations （P〈0. 05）. The previous 20 cases of missense mutations can be described as either multiple SNP group （with T10873C or T11944C） or nonmultiple SNP group. The percentage of a range and a plus b range of multiple SNP group of sperm was significantly higher than the non-multiple SNP group（P〈0.05）. Conclusions mtND4 gene mutation, especially the missense mutation may induce loss of sperm motility. The mutations of T10873Cand Tl1944C may be useful for sperm motility or counteract the influence for the sperm motility caused by these harmful mutations.

关 键 词：弱精子症 mtND4 基因突变 多态性 单核苷酸 

分 类 号：R698.2[医药卫生—泌尿科学]