Genetic heterogenecity of MTHFR C677T allele modulate hormonal dysfunction associated risk factors in the cases of male infertility

Male infertility is a serious problem in the developing world. Spermatogenesis is highly sensitive phenomenon due to involvement of environmental and genetic factors. The present study has been designed with the aim to evaluate the frequency of MTHFR C677T gene polymorphism, DNA copy number variations, hormone profile changes, and karyotypic alterations to evaluate the ‘risk factor’ in male infertility. Blood samples (n=72) were collected from clinically diagnosed cases of non obstructive azoospermia (NOA) and sever oligozoospermic patients with respective control. MTHFR C677T allele frequency and hormone profile (FSH, LH, Testosterone) was evaluated by ARMS-PCR and ELISA, respectively. Karyotypes were developed for confirmation of chromosomal aberrations as end point for genetic marker in infertility. Statistical analysis shows significant (p<0.05) variation in FSH, LH and testosterone in serum level in the cases of azoospermia and oligozoospermia. The frequency of CT allele shows (15.15%) genetic heterozygocity in the cases of azoospermia. Karyotype shows highest frequency of mosaicism (46, XY/46, XYY), suggesting chromosomal imbalance occurs due to non - disjunction events during meiosis I , which not only increase the frequency of heterozygocity of MTHFR gene but may also modulate endocrine dysfunction during spermatogenesis resulting in an increase of “risk factor” for developing male infertility.