Association between male infertility and genetic variability at the PON1/2 and GSTM1/T1 gene loci

Abstract

Environmental xenobiotics such as organophosphate pesticides are known factors involved in male infertility. Paraoxanase (PON) and glutathione transferase (GST) are involved in biotransformation of organophosphate pesticides. Interindividual genetic variations in biotransformation enzyme activities can lead to differences in the susceptibility to male infertility. This case-control study investigated associations between polymorphisms in the PON and GST genes (PON1–55/192, PON2–311, GSTM1/T1) and infertility. The study group consisted of 187 infertile men (86 with non-obstructive azoospermia (NOA) and 101 with oligoasthenoteratozoospermia (OAT)), whereas the control group comprised of 194 fertile men. Statistically significant differences were found in PON1–55MM genotype (chi-squared = 7.37; P = 0.02) and PON1–55M allele (chi-squared = 5.98; P = 0.01) distribution between the infertile and fertile men. A separate analysis revealed that significant differences in genotype frequencies were limited to the OAT group (chi-squared = 9.11, P = 0.01). However, no significant differences in genotype frequencies of other tested polymorphisms (PON1–192, PON2–311, GSTM1/T1) and male infertility were observed. The PON1–55M allele might represent a risk factor for infertility susceptibility in Slovenian men. Further studies with a larger sample size are needed to confirm these findings. Male infertility affects approximately 10% of the male adult population. Environmental xenobiotics such as organophosphate pesticides are known factors involved in male infertility. Enzymes, like paraoxanase (PON) and glutathione transferase (GST) are involved in the biotransformation of organophosphate pesticides. Therefore interindividual genetic variations in biotransformation enzyme activities can lead to differences in the susceptibility to male infertility. We conducted a case–control study to investigate the association between polymorphisms in the PON and GST genes (PON1–55/192, PON2–311, GSTM1/T1) and infertility in 381 Slovene Caucasian men. The study group consisted of 187 infertile men: 86 with non-obstructive azoospermia and 101 with oligoasthenoteratozoospermia, whereas the control group comprised of 194 proven fertile men. We found statistically significant differences in the PON1–55 genotype (chi-squared (2 df) = 7.37; p = 0.02) and allele (chi-squared (1 df) = 5.98; P = 0.01) distribution between the infertile and fertile men; a separate analysis of patients with azoospermia and oligoasthenoteratozoospermia revealed that significant differences in genotype frequencies were limited to the oligoasthenoteratozoospermia group (chi-squared = 9.11, P = 0.01), which also after applying Benjamini-Hochberg correction remained significant. No significant differences in frequencies of genotypes of other tested polymorphisms (PON1–192, PON2–311, GSTM1/T1) and male infertility were observed. This case–control study found that the PON1–55M allele might represent a risk factor for infertility susceptibility in Slovenian men. Further studies on larger sample size are needed to confirm our findings.