Gómez-Carballa Alberto, Pardo-Seco Jacobo, Martinón-Torres Federico, Salas Antonio
Unidade de Xenética, Departamento de Anatomía Patolóxica e Ciencias Forenses, Instituto de Ciencias Forenses, Facultade de Medicina, Universidade de Santiago de Compostela, Galicia, Spain.
GenPoB Research Group, Instituto de Investigaciones Sanitarias (IDIS), Hospital Clínico Universitario de Santiago, Santiago de Compostela, Galicia, Spain.
J Hum Genet. 2017 Mar;62(3):361-371. doi: 10.1038/jhg.2016.130. Epub 2016 Dec 1.
Infertility has a complex multifactorial etiology and a high prevalence worldwide. Several studies have pointed to variation in the mitochondrial DNA (mtDNA) molecule as a factor responsible for the different disease phenotypes related to infertility. We analyzed 53 mitogenomes of infertile males from Galicia (northwest Spain), and these haplotypes were meta-analyzed phylogenetically with 43 previously reported from Portugal. Taking advantage of the large amount of information available, we additionally carried out association tests between patient mtDNA single-nucleotide polymorphisms (mtSNPs) and haplogroups against Iberian matched controls retrieved from The 1000 Genomes Project and the literature. Phylogenetic and association analyses did not reveal evidence of association between mtSNPs/haplogroups and infertility. Ratios and patterns in patients of nonsynonymous/synonymous changes, and variation at homoplasmic, heteroplasmic and private variants, fall within expected values for healthy individuals. Moreover, the haplogroup background of patients was variable and fits well with patterns typically observed in healthy western Europeans. We did not find evidence of association of mtSNPs or haplogroups pointing to a role for mtDNA in male infertility. A thorough review of the literature on mtDNA variation and infertility revealed contradictory findings and methodological and theoretical problems that overall undermine previous positive findings.
不孕症病因复杂，具有多因素性，在全球范围内患病率较高。多项研究指出，线粒体DNA（mtDNA）分子的变异是导致与不孕症相关的不同疾病表型的一个因素。我们分析了来自西班牙西北部加利西亚地区的53名不育男性的线粒体基因组，并将这些单倍型与之前葡萄牙报告的43个单倍型进行了系统发育的荟萃分析。利用现有的大量信息，我们还对从千人基因组计划和文献中获取的伊比利亚匹配对照，开展了患者mtDNA单核苷酸多态性（mtSNP）和单倍群之间的关联测试。系统发育分析和关联分析均未发现mtSNP/单倍群与不孕症之间存在关联的证据。患者非同义/同义变化的比率和模式，以及纯合、杂合和私有变异的情况，均在健康个体的预期值范围内。此外，患者的单倍群背景具有多样性，与健康西欧人通常观察到的模式非常吻合。我们没有发现mtSNP或单倍群存在关联的证据，表明mtDNA在男性不育症中不起作用。对有关mtDNA变异与不孕症的文献进行全面回顾后发现，研究结果相互矛盾，且存在方法和理论问题，总体上削弱了之前的阳性研究结果。
