Single-nucleotide polymorphisms in the promoter region influence the expression of the human follicle-stimulating hormone receptor

Objective

To characterize novel single-nucleotide polymorphisms (SNPs) in the human FSH receptor (FSHR) promoter region.

Design

Retrospective and basic research study.

Setting

University hospital.

Patients

Women (202 from Germany and 55 from Indonesia) with male or tubal factor infertility undergoing controlled ovarian stimulation for IVF treatment.

Interventions

None.

Main Outcome Measure(s)

Frequency, distribution, and correlation with clinical data of the SNPs. Dual luciferase assays and electrophoretic mobility shift assays (EMSA).

Result(s)

We identified two SNPs and three mutations in the promoter region of the human FSHR which could be allocated to positions −29, −37, −114, −123, and −138 upstream of the translational initiation codon. One SNP showed a high incidence (−29: 44%, n = 202), but no correlation with basal FSH serum levels or ovarian response with the SNP at position −29 was found. Luciferase reporter assays, using pGL3 vector constructs, showed that mutations at positions −37 and −138 lead to significantly higher promoter activity. EMSA indicate that putative binding sites for transcription factors are affected by the SNPs.

Conclusions

The newly identified SNPs do not seem to influence clinical parameters substantially, but modulate expression of the FSHR via changes in transcription factor binding sites.

Key Words:  FSH receptor , promoter region , single-nucleotide polymorphisms