A Common Single Nucleotide Polymorphism in Exon 10 of the Human Follicle Stimulating Hormone Receptor Is a Major Determinant of Length and Hormonal Dynamics of the Menstrual Cycle

Rr, Greb; Grieshaber, K; Gromoll, Jörg; Sonntag, Barbara; Nieschlag, Eberhard; Kiesel, L.; Simoni, Manuela

doi:10.1210/jc.2004-2268

Cited by 139 publications

(112 citation statements)

References 32 publications

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“…In females, these SNPs have been shown to influence serum FSH levels during the follicular phase of the menstrual cycle [42]. Our results indicated that there was no association between these SNPs and the mean value of baseline FSH, which was a result inconsistent with the findings of Sudo et al [16], and also, we found no association between 307 and 680 SNPs and the mean value of LH, E2, and PRL levels in infertile women.…”

Section: Discussioncontrasting

confidence: 93%

Impact of follicle-stimulating hormone receptor variants in female infertility

Ilgaz

Aydos

Karadağ

et al. 2015

J Assist Reprod Genet

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Purpose Follicle-stimulating hormone (FSH) and its receptor play a major role in the development of follicles and regulation of steroidogenesis in the ovary and spermatogenesis in the testis. We aim to analyze the role of FSHR gene variants (single nucleotide polymorphisms (SNPs) in exon 10 (codon 307 and 680) and in the core promoter region (at position −29) and Ala189Val inactivating mutation) in Turkish infertile women. There were studies analyzing the effects of the SNPs in exon 10 (codon 307 and 680) and in the core promoter region (at position −29) of the FSHR gene on spermatogenesis, but to our knowledge, there were no studies analyzing the effects of these three SNP combinations on female fertility. Methods In this study, the allelic, genotype, and haplotype frequency distributions of these three SNPs in the FSHR gene were analyzed in 102 infertile women and 99 unrelated healthy control individuals. The distribution of the polymorphisms was conformed by Hardy-Weinberg equilibrium test. Results There were no statistical differences (P>0.05) in the allele, genotype, and haplotype frequencies of the polymorphisms and FSH, luteinizing hormone (LH), estradiol (E2), and prolactin (PRL) levels between the infertile patients and the controls. However, a significant relation was found between 307 SNP GA genotype and FSH level ≥12. We did not find any homozygous or heterozygote mutations in infertile patients and healthy fertile controls. Conclusion The present study was the first study analyzing gma mutation and the polymorphism of the FSHR core promoter at position −29 alone and in combination with the two common SNPs in exon 10 in Turkish infertile women population. These findings indicate the significance of Ala307Thr GA genotype may be a predictive marker for poor ovarian reserve and infertility.

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Section: Discussioncontrasting

confidence: 93%

Impact of follicle-stimulating hormone receptor variants in female infertility

Ilgaz

Aydos

Karadağ

et al. 2015

J Assist Reprod Genet

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“…27,28 Nakamura et al 13 reported on a patient with primary amenorrhea but normal sized ovaries containing some small antral follicles. These follicles reacted to high doses of hMG injection.…”

Section: Discussionmentioning

confidence: 99%

An unbalanced translocation unmasks a recessive mutation in the follicle-stimulating hormone receptor (FSHR) gene and causes FSH resistance

et al. 2010

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Follicle-stimulating hormone (FSH) mediated by its receptor (FSHR) is pivotal for normal gametogenesis. Inactivating FSHR mutations are known to cause hypergonadotropic hypogonadism with disturbed follicular maturation in females. So far, only very few recessive point mutations have been described. We report on a 17-year-old female with primary amenorrhea, hypergonadotropic hypogonadism and disturbed folliculogenesis. Chromosome analysis detected a seemingly balanced translocation 46,XX,t(2;8)(p16.3or21;p23.1)mat. FSHR sequence analysis revealed a novel non-synonymous point mutation in exon 10 (c.1760C4A, p.Pro587His), but no wild-type allele. The mutation was also found in the father, but not in the mother. Furthermore, molecular-cytogenetic analyses of the breakpoint region on chromosome 2 showed the translocation to be unbalanced, containing a deletion with one breakpoint within the FSHR gene. The deletion size was narrowed down by array analysis to approximately 163 kb, involving exons 9 and 10 of the FSHR gene. Functional studies of the mutation revealed the complete lack of signal transduction presumably caused by a changed conformational structure of transmembrane helix 6. To our knowledge, this is the first description of a compound heterozygosity of an inactivating FSHR point mutation unmasked by a partial deletion. This coincidence of two rare changes caused clinical signs consistent with FSH resistance.

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“…G −29 A, A 919 G (Thr 307 Ala) and A 2039 G (Asn 680 Ser) polymorphisms have been extensively studied by different investigators. It was reported that the polymorphism A 2039 G is associated with high basal FSH levels in women undergoing Assisted Reproductive Technology (ART) programme [17][18][19][20][21][22]. Recently, we have reported association of FSHR gene polymorphism (A 919 G, G −29 A) with altered ovarian response in subjects undergoing gonadotropin treatment during ART programme [23,24].…”

Section: Introductionmentioning

confidence: 94%

“…Primary amenorrhea subjects (n=48) Secondary amenorrhea subjects (n=38) response of the ovary to exogenous FSH [17,18,20,22]. However, a few studies have refuted this view [22,33].…”

Section: Hormonementioning

confidence: 99%

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Follicle stimulating hormone receptor gene variants in women with primary and secondary amenorrhea

Achrekar

Modi

Meherji

et al. 2010

J Assist Reprod Genet

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Purpose This retrospective study was designed to analyze the FSHR gene variants in subjects with primary and secondary amenorrhea with hypergonadotropic hypogonadism. Materials and methods Eighty six women with primary or secondary amenorrhea and 100 normally cycling proven fertile women of Indian origin were retrospectively studied. These subjects were systematically screened for entire FSHR gene. Results The frequency distribution of polymorphism at −29 position of FSHR gene is altered in women with primary and secondary amenorrhea as compared to controls. AA genotype at −29 position of FSHR gene seems to be associated with increased serum FSH levels in the study subjects. We have identified a novel homozygous mutation C 1723 T (Ala 575 Val) in one woman with primary amenorrhea. Conclusions Our findings suggest that increased serum FSH levels in subjects with primary amenorrhea correlated to FSHR genotype at position −29. We identified a novel homozygous mutation C 1723 T (Ala 575 Val) in a woman with primary amenorrhea.

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A Common Single Nucleotide Polymorphism in Exon 10 of the Human Follicle Stimulating Hormone Receptor Is a Major Determinant of Length and Hormonal Dynamics of the Menstrual Cycle

Abstract: The FSH receptor Ser680/Ser680 genotype is associated with higher ovarian threshold to FSH, decreased negative feedback of luteal secretion to the pituitary during the intercycle transition, and longer menstrual cycles.

Cited by 139 publications

References 32 publications

Impact of follicle-stimulating hormone receptor variants in female infertility

Impact of follicle-stimulating hormone receptor variants in female infertility

An unbalanced translocation unmasks a recessive mutation in the follicle-stimulating hormone receptor (FSHR) gene and causes FSH resistance

Follicle stimulating hormone receptor gene variants in women with primary and secondary amenorrhea

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