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Abstract

Asian Journal of Andrology (2009) 11: 333-341. doi: 10.1038/aja.2008.27; published online19 January 2009.

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

Kentaro Ichioka1, Kanji Nagahama1, Kazutoshi Okubo1, Takeshi Soda1, Osamu Ogawa1 and Hiroyuki Nishiyama1

1 Department of Urology, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Ja

Correspondence: Dr Osamu Ogawa, 54, Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. Fax: +81-75-761-3441 E-mail: ogawao@kuhp.kyoto-u.ac.jp

Received 23 April 2008; Revised 20 August 2008; Accepted 10 October 2008; Published online 19 January 2009.

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.

Keywords: genetic polymorphism, GSTM1, GSTT1, male infertility, NQO1, SOD2, varicocele testis

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