Abstract
Many studies have been performed to explore the role of xenobiotic metabolizing gene variants and male infertility risk. However, the results remain inconclusive and contradictory. Therefore, the objective of the present study was to investigate the association among 16 genes and its 24 variants (CAT rs1001179, rs7943316, SOD2 rs4880, GPX1 rs1050450, CYP1A1 rs1048943, rs4646903, GSTP1 rs1695, MTHFR rs1801133, rs1801131, rs2274976, rs2066472, MTHFD1 rs2236225, MTRR rs1801394, CYP2D6 rs3892097, PON1 rs854560, rs662, PON2 rs7493, NAT2 rs1799930, NRF2 rs6721961, AHR rs2066853, rs1476080, rs6960165, null GSTM1, null GSTT1) involved in xenobiotic metabolism and their correlation with male infertility. A literature search was done using PubMed, Google Scholar, and Science Direct. Meta-analysis was conducted using Review Manager 5.3 software. Genotype-tissue expression (GTEx) portal and RegulomDB were used to determine genotype and tissue expression. Pathogenicity of significant gene variants was determined using I-Mutant 2.0, PolyPhen 2, SNP & GO, SIFT, and CADD tools. A total of 106 studies were selected for the present study to analyze 16 genes and their variants. SOD2 rs4880, CYP1A1 rs4646903, MTHFR rs1801133, rs1801131, rs2274976, PON1 rs854560, NRF2 rs6721961, and null GSTM1 gene variants are associated with increased risk of male infertility. SOD2 rs4880 and MTHFR rs1801133, rs1801131, rs2274976 are found to decrease the stability of the protein. However, no significant association was observed between CAT rs1001179, rs7943316, GPX1 rs1050450, CYP1A1 rs1048943,GSTP1 rs1695,MTHFR rs2066472, MTHFD1 rs2236225, MTRR rs1801394, CYP2D6 rs3892097, PON1 rs662, PON2 rs7493, NAT2 rs1799930, AHR rs2066853, rs1476080, rs6960165, null GSTT1 gene polymorphisms and the risk of male infertility.