The contribution of genetic variations of aryl hydrocarbon receptor pathway genes to male factor infertility

Abstract

Objective: Todeterminewhetherthepolymorphismsinarylhydrocarbonreceptor(AHR),arylhydrocarbonrecep- tor repressor (AHRR), and aryl hydrocarbon receptor nuclear translocator (ARNT) genes are associated with male factor infertility. Design: An association study. Setting: University research laboratory and andrology clinic. Patient(s): ThesubjectswereinfertileEstonianmen(n1⁄4112)withazoospermiaoroligozoospermiaandcontrols (n 1⁄4 212) with normal sperm parameters. Intervention(s): Blood samples were obtained for DNA extraction and genotyping. MainOutcomeMeasure(s): AHR(Arg554Lys),AHRR(Pro185Ala),andARNT(G/Callele)polymorphismswere genotyped using allele-specific polymerase chain reaction. Allele and genotype frequencies were compared between infertile men and controls and separately in the normozoospermia, oligozoospermia, and azoospermia groups. Result(s): The AHRR Ala185Ala genotype was implicated in susceptibility to male factor infertility. Ala/Ala genotype frequency increased in the following order: normozoospermia (18.0%), oligozoospermia (26.0%), azoospermia (42.1%). Allele and genotype frequencies of AHR and ARNT polymorphisms were similar between cases and controls. Conclusion(s): WedemonstratedthattheAHRRPro185Alapolymorphismcontributedtoapredispositiontomale factor infertility in the Estonian population. A greater prevalence of the Ala/Ala genotype was found among infer- tile patients.