The polymorphism (- 600 C > A) of CpG methylation site at the promoter region of CYP17A1 and its association of male infertility and testosterone levels

• The − 600C > A (rs17115149) at the promoter region of CYP17A1 was significantly associated with Oligoasthenoteratozoospermia.
• The − 600C > A polymorphism is statistically significant associated with testosterone levels from infertile males (n = 197, P < 0.05).
• The − 600C > A polymorphism is located at the promoter region of CYP17A1 was CpG methylation site for its expression.
• Novel CYP17A1 promoter polymorphism may signify a genetic risk factor for male infertility.

Cytochrome P450, family 17, subfamily A, polypeptide 1 (CYP17A1) is a key regulatory enzyme in the steroidogenic pathway. The functional and clinical relevance of novel CYP17A1 promoter single nucleotide polymorphism (- 600 C > A, rs17115149) was investigated with male infertility. Case-control association study of CYP17A1 from 456 infertile men performed with 465 normal fertile men. The rs17115149 at the promoter region of CYP17A1 was significantly associated with Oligoasthenoteratozoospermia (OAT, P = 0.0015, n = 265). 5-aza-dC treatment to B lymphocyte cells increased the CYP17A1 expression. Direct bisulfite sequencing of five human tissues showed that the rs17115149 is located at - 600 bp (- 600C > A) before transcription start site within the CpG islands of CYP17A1 promoter. This − 600 Cytosine of CpG site was highly methylated in colon and stomach tissues, but low methylated in adrenal gland, kidney and testis with higher CYP17A1 RNA expression. Especially, this polymorphism is statistically significant associated with testosterone levels from infertile males (n = 197, P < 0.05). CYP17A1 promoter polymorphism (rs17115149, − 600C > A) is a functional regulatory SNP which associated with its expression possibly by epigenetic pathway, which may signify a genetic risk factor for male infertility.