Systematic review and meta-analysis of the genetic association between protamine polymorphism and male infertility

While several previous studies have proposed an association between male infertility and protamine polymorphism, the reported findings have shown some inconsistency. To evaluate the potential association between the two most common single nucleotide polymorphisms (rs2301365 and rs1646022) in protamine and male infertility, we performed a meta-analysis involving 2713 cases and 2086 controls from 15 published case-controlled studies. Overall, our analysis showed significant associations between the specific protamine single-nucleotide polymorphism (rs2301365) and male infertility, and this association was indicated by all of the models we tested. Subgroup analysis revealed significant associations with a Caucasian background, PCR sequence, population-based, case size of > 150 and case size of < 150 subgroups. Similarly, significant associations were found between rs1646022 and male infertility in the hospital population and case size of < 200 subgroups. However, trial sequential analysis showed that the number of patients in the study did not reach optimal information size. Further studies with larger sample sizes are now warranted to clarify the potential roles of the two protamine polymorphisms in the pathogenesis of male infertility. This may help us to understand the precise molecular mechanisms underlying the effect of protamines upon male infertility.