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Association of MTHFR, NFKB1, NFKBIA, DAZL and CYP1A1 gene polymorphisms with risk of idiopathic male infertility in a Han Chinese population.

In this study, we investigated the association between six genetic polymorphisms (MTHFR C677T and A1298C, NFKB1 -94ins/del ATTG, NFKBIA 3'UTR A>G, DAZL A386G (T54A) and CYP1A1 T3801C) and the risk of idiopathic male infertility in a Chinese population. A case-control study comprising 1,759 idiopathic male infertile patients of Han Chinese ethnicity and 1,826 healthy fertile control individuals was carried out. Genotypes of all polymorphisms were determined via PCR-RFLP. Chi-squared test and logistic regression modeling were performed to identify the association of the polymorphisms with idiopathic male infertility. It was found that the heterozygous and variant genotypes of the following polymorphisms were significantly associated with an increased idiopathic male infertility risk: MTHFR C677T (heterozygous OR=1.266 [1.089, 1.470], P=0.002; variant OR=1.384 [1.138, 1.684], P=0.001), MTHFR A1298C (heterozygous OR=1.233 [1.071, 1.419], P=0.004; variant OR=1.564 [1.183, 2.068], P=0.002), and CYP1A1 T3801C (heterozygous OR=1.163 [1.007, 1.344], P=0.040; variant OR=1.232 [1.005, 1.510], P=0.045). When genotypes of non-significant polymorphisms were combined and analyzed, it was found that the combination between variant DD genotype of NFKB1 -94ins/del ATTG polymorphism and heterozygous AG genotype of DAZL A386G polymorphism was significantly associated with a reduced idiopathic male infertility risk (OR=0.588 [0.376, 0.919], P=0.02). In summary, we have successfully identified the association (or lack thereof) between the polymorphisms and idiopathic male infertility risk.