Synergistic effects of TIMP2-418G/C and MMP9-1562C/T variants on the male infertility risk.

Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) involve in the degradation of the extracellular matrix (ECM) that imbalances their activity and may lead to various diseases. The present study aims to evaluate the association between MMP9-1562C/T and TIMP2-418G/C variants and synergistic effects of both variants on male infertility in an Iranian population. We analyzed these polymorphisms in 101 infertile men and 106 fertile men as a control group using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Based on the obtained results, no considerable association was observed in MMP9-1562C/T polymorphism frequency between infertile men and controls while frequencies of TIMP2-418G/C variant were significantly different in infertile and control groups (P = 0.028). Men with CC, GC and CC + GC genotypes for TIMP2-418G/C polymorphism had an increased risk of infertility compared to men with GG genotype [OR = 1.85, 95% CI (0.917-3.734, P = 0.086), OR = 1.94, 95% CI (1.098-3.437, P = 0.023) and OR = 2.053 95% CI (1.179-3.577, P = 0.011), respectively]. Also, in the presence of both TIMP2-418C and MMP9-1562T alleles the male infertility risk was significantly increased (P = 0.032). The current study suggests that the variation of TIMP2 gene and its interaction with MMP9 gene might be associated with male infertility. However, to confirm these findings, further studies are required in different ethnicities and with a larger sample size.