A single-nucleotide polymorphism of the DAZL gene promoter confers susceptibility to spermatogenic failure in the Taiwanese Han

Deleted in AZoospermia-like (DAZL) is an autosomal homologue of Y chromosome-linked DAZ gene located on chromosome 3p24. DAZL is only expressed in the gonads and is critical to germ cell development in different species. However, the regulation of DAZL has not been explored. Reporter assays, electrophoretic mobility shift assays, supershift assays and bisulfate sequencing were used to identify the core promoter region of DAZL. Sequence analysis was used to identify single-nucleotide polymorphisms (SNPs) in the promoter region. A total of 337 infertile men with abnormal semen parameters and 203 fertile men with normal semen parameters were subjected to sequence analysis of the DAZL promoter region. The DAZL gene core promoter is located 1 kb upstream of the transcription start site. Three SNPs (−792G>A, −669A>C and −309T>C) were identified in our population. Of these three SNPs, −792G>A was more prevalent in the infertile men (P= 0.0005). Quantitative analysis revealed that genotypes of −792G>A had effects on sperm concentration (P= 0.0025) and motility (P= 1.5 × 10–7). The G to A substitution was associated with decreased binding of the nuclear respiratory factor-1 (NRF-1) to the promoter region and decreased reporter gene activity. We have identified the core promoter of the human DAZL gene. We also provide preliminary evidence for the role of a novel SNP of the DAZL gene promoter in human spermatogenic failure.