Isoforms and single nucleotide polymorphisms of the FSH receptor gene: implications for human reproduction

Abstract

The FSH receptor shows three single nucleotide polymorphisms (SNPs), one in the promoter and two in exon 10. In addition, the FSH receptor mRNA undergoes extensive alternative splicing. While no physiological role for the SNP in the promoter and for alternative spliced isoforms has been demonstrated so far, the SNPs in exon 10 result in four discrete allelic variants characterized by the amino acid combinations Thr³⁰⁷-Asn⁶⁸⁰, Ala³⁰⁷-Ser⁶⁸⁰, Ala³⁰⁷-Asn⁶⁸⁰ and Thr³⁰⁷-Ser⁶⁸⁰. Several studies have demonstrated that the first two allelic variants are very frequent (∼60 and 40% respectively) in the Caucasian population. The rarer Ala³⁰⁷-Asn⁶⁸⁰ and Thr³⁰⁷-Ser⁶⁸⁰ variants are much less frequent (307-Ser⁶⁸⁰ variant seems to be associated with significantly higher basal serum FSH levels and with a higher amount of FSH required for ovarian stimulation in women undergoing assisted reproduction. This suggests that the FSH receptor genotype can influence the ovarian response to FSH stimulation. The presence of SNPs in the FSH receptor gene capable of modifying FSH action paves the way for future patient-tailored, genotype-based hormone therapies.