title: Synergism between the N-acetyltransferase 2 gene and oxidant exposure increases the risk of idiopathic male infertility.
abstract: N-acetyltransferase (NAT2) is a phase-II xenobiotic-metabolizing enzyme participating in the detoxification of toxic arylamines, aromatic amines and hydrazines. The present study was designed to investigate whether two common single-nucleotide polymorphisms (SNP) of the NAT2 gene (481C>T, rs1799929; 590G>A, rs1799930) are associated with susceptibility to idiopathic male infertility and to assess if the risk is modified by oxidant and antioxidant exposures. A total 430 DNA samples (203 infertile patients and 227 fertile men) were genotyped for the polymorphisms by PCR and restriction fragment length polymorphism. No association was found between the NAT2 polymorphisms and idiopathic male infertility. However, gene-environment interaction analysis revealed that a low-acetylation genotype, 590GA, was significantly associated with increased disease risk in men who had environmental risk factors such as cigarette smoking (OR 1.71, 95% CI 1.02-2.87, P = 0.042), alcohol abuse (OR 2.14, 95% CI 1.08-4.27, P = 0.029) and low fruit/vegetable intake (OR 1.68, 95% CI 1.01-2.79, P = 0.04). This pilot study found, as far as is known for the first time, that the polymorphism 590G>A of NAT2 is a novel genetic marker for susceptibility to idiopathic male infertility, but the risk is potentiated by exposure to various environmental oxidants.
authors.affiliation: Department of Biology, Medical Genetics and Ecology, Kursk State Medical University, Kursk, Russian Federation; Family Planning and Reproductive Health Clinic, Regional Perinatal Center, Kursk, Russian Federation.
authors.forename: Sergey L
authors.initials: SL
authors.lastname: Yarosh
authors.affiliation: Department of Zoology and Theory of Evolution, Kursk State University, Kursk, Russian Federation.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Kokhtenko
authors.affiliation: Department of Medical Biological Disciplines, Belgorod State National Research University, Belgorod, Russian Federation.
authors.forename: Mikhail I
authors.initials: MI
authors.lastname: Churnosov
authors.affiliation: Department of Pathophysiology, Sumy State University, Sumy, Ukraine.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Ataman
authors.affiliation: Department of Biology, Medical Genetics and Ecology, Kursk State Medical University, Kursk, Russian Federation.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Solodilova
authors.affiliation: Department of Biology, Medical Genetics and Ecology, Kursk State Medical University, Kursk, Russian Federation. Electronic address: polonikov@rambler.ru.
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Polonikov
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000009:adverse effects*; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D004032:Diet; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007248:Infertility, Male / Q000209:etiology* / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*
chemical_list: D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human
keywords: N-acetyltransferase 2 (NAT2); alcohol abuse; cigarette smoking; fruit and vegetable intake; gene–environment interaction; idiopathic male infertility