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.
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We are very grateful to all members of Department of Urology, CHA general hospital, Seoul, Korea for recruiting the infertile males who participated in this study. We thank Dr Lee, Hong Gu of the Department of Medicine, Seoul National University for the human adrenal corticocarcinoma NCI-H295R cells. This study was supported by a grant ( A120520 ) from the Korea Healthcare Technogy R&D Project, Ministry of Health and Welfare, Republic of Korea .
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