Genetic polymorphisms in glutathione S-transferase T1 affect the surgical outcome of varicocelectomies in infertile patients

Abstract

Glutathione S-transferases (GSTs), superoxide dismutase 2 (SOD2) and NAD(P)H:quinone oxidoreductase 1 (NQO1) are anti-oxidant enzyme genes. Polymorphisms of GSTs, SOD2 and NQO1 have been reported to influence individual susceptibility to various diseases. In an earlier study, we obtained preliminary findings that a subset of glutathione S-transferase T1 (GSTT1)-wt patients with varicocele may exhibit good response to varicocelectomy. In this study, we extended the earlier study to determine the distribution of genotype of each gene in the infertile population and to evaluate whether polymorphism of these genes affects the results of surgical treatment of varicocele. We analyzed 72 infertile varicocele patients, 202 infertile patients without varicocele and 101 male controls. Genotypes of GSTs were determined by polymerase chain reaction (PCR). Genotyping of SOD2 and NQO1 was performed using the PCR-restriction fragment length polymorphism (PCR-RFLP) method. A significantly better response to varicocelectomy was found in patients with the GSTT1-wt genotype (63.2%) and NQO1-Ser/Ser genotype (80.0%) than in those with GSTT1-null genotype (35.3%) and NQO1-Pro/Pro or NQO1-Pro/Ser genotype (45.2%), respectively. The frequencies of glutathione S-transferase M1/T1, SOD2 and NQO1 genotypes did not differ significantly among the varicocele patients, idiopathic infertile patients and male controls. GSTT1 genotype is associated with improvement of semen parameters after varicocelectomy. As the number of patients with NQO1-Ser/Ser genotype was not sufficient to reach definite conclusions, the association of NQO1 genotype with varicocelectomy requires further investigation.

Genetic Polymorphisms of Glutathione S‐Transferase M1, T1, and P1, and the Assessment of Oxidative Damage in Infertile Men With Varicoceles From Northwestern China

“…Previous studies have suggested that the frequency of the GSTM1 null genotype is significantly higher in infertile men than that in fertile men (Tirumala et al, 2010) and that the decline in the semen quality of individuals with idiopathic infertility is associated with the GSTM1 / GSTT1 null genotypes (Finotti et al, 2009). Furthermore, the improvement in the semen parameters in response to varicocelectomy is significantly higher in patients with the GSTT1 present genotype (Ichioka et al, 2009), and the susceptibility of sperm and seminal plasma to oxidative stress is significantly greater in idiopathic infertile men with the GSTM1 null genotype than in idiopathic infertile men with the GSTM1 present genotype (Aydemir et al, 2007). The GSTM1 and GSTT1 present genotypes are related to a favorable response to varicocelectomy (Okubo et al, 2005), and the GSTM1 null genotype appears to predispose the sperm of patients with varicoceles to increased oxidative damage (Chen et al, 2002).…”

Glutathione-S-transferase gene polymorphisms (GSTM1, GSTT1, GSTP1) and idiopathic male infertility: novel perspectives versus facts

“…2 Six case-control studies 1,3-7 were eligible concerning GSTM1 genotype (912 male infertility cases, 859 controls) and five casecontrol studies 1,4,6-8 were eligible concerning GSTT1 genotype (862 male infertility cases, 755 controls). All studies were conducted on Caucasian subjects except for one 6 in the case of GSTM1 polymorphism and two 6,8 in the case of GSTT1 polymorphism.…”

Association of the Glutathione S-transferases M1 and T1 polymorphism with male infertility: a meta-analysis

“…The characteristics of selected studies are summarized in Table 1. A total of 12 eligible studies met the inclusion criteria, including 11 studies for GSTM1 [14,15,[25][26][27][28][29][30][31][32][33] and 9 ones for GSTT1 [17,26,27,[29][30][31][32][33]. All the included studies were case-control studies.…”