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.


METHODS
Retrospective and basic research study.


METHODS
University hospital.


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


METHODS
None.


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


RESULTS
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.
Wunsch
Alain
A
Institute of Reproductive Medicine, University Hospital, Münster, Germany.
Ahda
Yuni
Y
Banaz-Yaşar
Ferya
F
Sonntag
Barbara
B
Nieschlag
Eberhard
E
Simoni
Manuela
M
Gromoll
Jörg
J
D000704:Analysis of Variance; D000818:Animals; D001483:Base Sequence / Q000235:genetics; D002478:Cells, Cultured; D005260:Female; D043373:Follicle Stimulating Hormone, Human / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011962:Receptors, FSH / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D012189:Retrospective Studies
D043373:Follicle Stimulating Hormone, Human; D011962:Receptors, FSH