Association of male infertility with Pro185Ala polymorphism in the aryl hydrocarbon receptor repressor gene: implication for the susceptibility to dioxins.

OBJECTIVE: To examine whether Arg554Lys polymorphism in the gene for aryl hydrocarbon receptor (AHR) and/or Pro185Ala polymorphism in the gene for aryl hydrocarbon receptor repressor (AHRR) constitutes a susceptibility locus for dioxin-related male infertility.
DESIGN: Association study of male infertility with polymorphisms.
SETTING: National research institute and university hospitals. PATIENT(S): 123 Japanese men with azoospermia or severe oligozoospermia and 112 men with proven fertility. INTERVENTION(S): Polymorphism analysis. MAIN OUTCOME MEASURE(S): The allele and genotype frequencies between infertile men and controls. RESULT(S): The allele and genotype frequencies of the AHR polymorphism were comparable between infertile men and controls. By contrast, although the difference in the allele frequency of the AHRR polymorphism did not reach a significant level, the genotype frequency was statistically significantly different between the two groups of men. Furthermore, the statistical difference became more significant when the frequency was compared between the Pro/Pro genotype and the Pro/Ala plus Ala/Ala genotype. CONCLUSION(S): The Pro185Ala polymorphism in AHRR may constitute a susceptibility locus for dioxin-related male infertility. It appears that the negative feedback effect of AHRR on dioxin-related signaling is weaker for the proline allele than for the alanine allele, and that the hypomorphic function of the proline allele exerts a recessive adverse effect on male fertility.