RESUMO
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.
Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Arilamina N-Acetiltransferase/genética , Infertilidade Masculina/etiologia , Fumar/efeitos adversos , Adulto , Dieta , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Infertilidade Masculina/genética , Masculino , Polimorfismo de Nucleotídeo Único , Fatores de RiscoRESUMO
The study was designed to investigate the associations of polymorphisms Ile462Val and 3801T>C of the cytochrome P450 1A1 (CYP1A1) gene with idiopathic male infertility (IMI) and to assess the impact of smoking status on the relationship between the polymorphisms and the susceptibility to the disease. DNA samples from 203 patients with IMI and 227 fertile men were genotyped for the polymorphisms by a polymerase chain reaction and restriction fragment length polymorphism methods. We found for the first time that the increased risk of IMI in carriers of genotype 462Ile/Val of the CYP1A1 gene occurred only in smoker men (odds ratio [OR] = 1.91; 95% confidence interval [CI] 1.01-3.59), whereas nonsmoker men did not have the risk of infertility (OR = 1.58; 95% CI 0.66-3.76). The results of our study demonstrate that the analysis of gene-environment interactions is necessary to explain conflicting results of genetic studies of IMI and to improve our understanding of the mechanisms of the disease.
Assuntos
Citocromo P-450 CYP1A1/genética , Fertilidade/genética , Interação Gene-Ambiente , Infertilidade Masculina/genética , Polimorfismo de Nucleotídeo Único , Fumar/efeitos adversos , Adulto , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Frequência do Gene , Predisposição Genética para Doença , Humanos , Infertilidade Masculina/enzimologia , Infertilidade Masculina/etiologia , Desequilíbrio de Ligação , Modelos Logísticos , Masculino , Razão de Chances , Fenótipo , Fatores de RiscoRESUMO
This study was designed to investigate the association between null polymorphisms of glutathione S-transferase (GST) M1 and T1 genes and idiopathic male infertility in a Russian population including 203 infertile and 227 fertile men. The nondeletion genotype of the GSTT1 gene was found to be strongly associated with the increased risk of idiopathic male infertility and asthenozoospermia.