Single nucleotide polymorphisms in the promoter and coding region of the FSH receptor gene determine four haplotypes differently distributed in normozoospermic and azoospermic men

Abstract

The human follicle-stimulating hormone (FSH) receptor possesses single nucleotide polymorphims (SNPs) in exon 10 (at codons 307 and 680) which influence serum FSH levels in women but not in men. In the present study we extended our previous analysis to 438 men with non-obstructive azoospermia and 304 controls. In addition, we analysed a novel, common SNP in the core promoter of the FSHR gene (at position –29). SNPs were determined by the Taqman allelic discrimination assay. No significant difference in the frequency of the polymorphism at position 680 (Asn/Asn, Asn/Ser, Ser/Ser) between azoo- and normozoospermic men was found. As for the SNP at position –29 (A/G), the A–29 was less frequent than the G–29 allele both in controls (25% vs. 75%) and in patients (30% vs. 70%) (p=NS). Considering the three SNPs together, the four most common allelic variants were found, i.e. A-Thr-Asn, G-Thr-Asn, A-Ala-Ser and G-Ala-Ser, combined into the 10 major combinations. A statistically significant difference in the allelic distribution between controls and azoospermic men was found (p<0.01 by Fisher's exact test) and the A-Ala-Ser haplotype was more frequent in patients (9.1%) than in controls (5.4%), while the G-Thr-Asn haplotype was less frequent in patients (33.1%) than in controls (40.6%). No significant correlation between serum FSH levels and FSHR allele was found. This study shows that the SNPs in the FSHR gene do not influence serum FSH levels in normal and azoospermic men. However, the different distribution of the FSHR alleles between controls and azoospermic men suggests that the A-Ala-Ser haplotype might represent a genetic factor contributing to phenotypic expression of severe spermatogenetic impairment.