Evaluation of 172 candidate polymorphisms for association with oligozoospermia or azoospermia in a large cohort of men of European descent

Background: In spite of tremendous efforts by a number of groups, the search for single nucleotide polymorphisms (SNPs) strongly associated with male factor infertility by means of gene re-sequencing studies has yielded few likely candidates. A recent pilot, genome-wide SNP association study (GWAS) identified a list of SNPs associated with oligozoospermia and azoospermia. This is an expanded follow-up study of the SNPs identified by the GWAS as well as other SNPs from previously published gene re-sequencing studies. Methods: On the basis of the pilot GWAS and SNPs with published associations with male infertility, 172 SNPs were genotyped in men with idiopathic azoospermia or oligozoospermia using the Illumina BeadXpress (R) platform. Results: Several SNPs were identified or confirmed to be significantly associated with oligozoospermia and/or azoospermia. More importantly, this follow-up study indicates that, at least in Caucasian men, no single common SNP accounts for a significant proportion of spermatogenic failure cases. Conclusions: The associations reported in this study are promising, but much larger genome-wide studies will be necessary to confidently validate these SNPs and identify novel SNPs associated with male infertility.