title: Polymorphisms in aryl hydrocarbon receptor gene are associated with idiopathic male factor infertility.
abstract: We wanted to determine whether genetic polymorphisms of aryl hydrocarbon receptor (AhR) gene are associated with susceptibility to male infertility. This study comprised 176 men with idiopathic infertility and 352 healthy fertile men who served as controls. Seven single-nucleotide polymorphisms (SNPs) of the AhR gene (rs2066853, rs1476080, rs10250822, rs10247158, rs2282885, rs6960165, and rs7811989) were selected and genotyped by the polymerase chain reaction-restriction fragment length polymorphism analysis. The serum levels of reproductive and thyroid hormones and inhibin B were also measured. After multiple regression analysis, 2 of the 7 studied SNPs were significantly associated with the occurrence of male infertility. Men with rs2066853 AA genotype had 33% decreased risk of being infertile (odds ratio [OR] = 0.67, 95% confidence interval [CI]: 0.46-0.87; P = .003). The C allele of rs2282885 was significantly associated with infertility risk, with an OR of 2.14 (95% CI: 1.64-3.72) for heterozygotes and 3.54 (95% CI: 2.25-5.84) for homozygotes. When haplotypes were composed of 7 AhR SNP sites, patients with AACACAG haplotype harbored more than 75% decreased risk of being infertile (OR = 0.21, 95% CI: 0.11-0.32; P = .001). Conversely, carriers of the AACACGA haplotype had more than 12-fold increased risk of being infertile (OR = 12.62, 95% CI: 2.77-52.74; P = .00001). Homozygosity for the rs2066853 A allele and rs2282885 C allele decreases and increases the risk of developing male infertility, respectively.
authors.affiliation: 1Clinical Center for Urological Disease Diagnosis and Private Clinic Specialized in Urological and Andrological Genetics, Tehran, Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Safarinejad
authors.forename: Nayyer
authors.initials: N
authors.lastname: Shafiei
authors.forename: Saba
authors.initials: S
authors.lastname: Safarinejad
mesh_terms: D000328:Adult; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005298:Fertility / Q000235:genetics*; D043373:Follicle Stimulating Hormone, Human / Q000097:blood; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007248:Infertility, Male / Q000097:blood / Q000235:genetics* / Q000503:physiopathology; D007265:Inhibins / Q000097:blood; D007492:Iran; D016015:Logistic Models; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D016017:Odds Ratio; D010641:Phenotype; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics*; D012307:Risk Factors; D013076:Sperm Count; D013081:Sperm Motility / Q000235:genetics; D013739:Testosterone / Q000097:blood; D013963:Thyroid Hormones / Q000097:blood
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D043373:Follicle Stimulating Hormone, Human; D007265:Inhibins; D007986:Luteinizing Hormone; D018336:Receptors, Aryl Hydrocarbon; D013739:Testosterone; D013963:Thyroid Hormones; C111235:AHR protein, human; C422364:inhibin B
keywords: aryl hydrocarbon receptor; genetics; male infertility; single-nucleotide polymorphisms; unexplained infertility