OBJECTIVE: To assess the pharmacogenetic potential of FSH for infertility treatment. DESIGN: Review of the literature and genomic databases. METHODS: Single-nucleotide polymorphism (SNP) assessed: rs6166 (c.2039A>G, p.N680S), rs6165 (c.919A>G, p.T307A), rs1394205 (c.-29G>A) in FSHR, and rs10835638 (c.-211G>T) in FSHB. Literature search via PubMed. Blast analysis of genomic information available in the NCBI nucleotide database. Comparison of allele frequency and haplotype distribution using the http://spsmart.cesga.estool. RESULTS: All these SNPs appear first in Homo, result in reduced FSH action, and are present with variable frequencies and combinations worldwide. Stringent clinical studies demonstrate that the FSHR genotype influences serum FSH levels and gonadal response in both sexes. Serum FSH levels depend on the -211G>T SNP, influencing transcriptional activity of the FSHB promoter. Genotypes reducing FSH action are overrepresented in infertile subjects. CONCLUSIONS: Although the clinical relevance of the FSHR polymorphisms alone is limited, the combination of FSHR and FSHB genotypes has a much stronger impact than either one alone in both sexes. About 20% of people are carriers of the alleles associated with lower serum FSH levels/reduced FSHR expression or activity, possibly less favorable for reproduction. Prospective studies need to investigate whether stratification of infertile patients according to their FSHR-FSHB genotypes improves clinical efficacy of FSH treatment compared with the current, naïve approach. A relative enrichment of less favorable FSHR-FSHB genotypes may be related to changes in human reproductive strategies and be a marker of some health-related advantage at the cost of reduced fertility.

Mechanisms in endocrinology: Genetics of FSH action: a 2014-and-beyond view / Simoni, Manuela; Casarini, Livio. - In: EUROPEAN JOURNAL OF ENDOCRINOLOGY. - ISSN 0804-4643. - STAMPA. - 170:(2014), pp. R91-R107. [10.1530/EJE-13-0624]

Mechanisms in endocrinology: Genetics of FSH action: a 2014-and-beyond view

SIMONI, Manuela;CASARINI, Livio
2014

Abstract

OBJECTIVE: To assess the pharmacogenetic potential of FSH for infertility treatment. DESIGN: Review of the literature and genomic databases. METHODS: Single-nucleotide polymorphism (SNP) assessed: rs6166 (c.2039A>G, p.N680S), rs6165 (c.919A>G, p.T307A), rs1394205 (c.-29G>A) in FSHR, and rs10835638 (c.-211G>T) in FSHB. Literature search via PubMed. Blast analysis of genomic information available in the NCBI nucleotide database. Comparison of allele frequency and haplotype distribution using the http://spsmart.cesga.estool. RESULTS: All these SNPs appear first in Homo, result in reduced FSH action, and are present with variable frequencies and combinations worldwide. Stringent clinical studies demonstrate that the FSHR genotype influences serum FSH levels and gonadal response in both sexes. Serum FSH levels depend on the -211G>T SNP, influencing transcriptional activity of the FSHB promoter. Genotypes reducing FSH action are overrepresented in infertile subjects. CONCLUSIONS: Although the clinical relevance of the FSHR polymorphisms alone is limited, the combination of FSHR and FSHB genotypes has a much stronger impact than either one alone in both sexes. About 20% of people are carriers of the alleles associated with lower serum FSH levels/reduced FSHR expression or activity, possibly less favorable for reproduction. Prospective studies need to investigate whether stratification of infertile patients according to their FSHR-FSHB genotypes improves clinical efficacy of FSH treatment compared with the current, naïve approach. A relative enrichment of less favorable FSHR-FSHB genotypes may be related to changes in human reproductive strategies and be a marker of some health-related advantage at the cost of reduced fertility.
2014
170
R91
R107
Mechanisms in endocrinology: Genetics of FSH action: a 2014-and-beyond view / Simoni, Manuela; Casarini, Livio. - In: EUROPEAN JOURNAL OF ENDOCRINOLOGY. - ISSN 0804-4643. - STAMPA. - 170:(2014), pp. R91-R107. [10.1530/EJE-13-0624]
Simoni, Manuela; Casarini, Livio
File in questo prodotto:
File Dimensione Formato  
153.pdf

Accesso riservato

Descrizione: Articolo principale
Tipologia: Versione pubblicata dall'editore
Dimensione 2.44 MB
Formato Adobe PDF
2.44 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
EJE-13-0624.pdf

Open access

Tipologia: Versione dell'autore revisionata e accettata per la pubblicazione
Dimensione 2.7 MB
Formato Adobe PDF
2.7 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1063419
Citazioni
  • ???jsp.display-item.citation.pmc??? 32
  • Scopus 95
  • ???jsp.display-item.citation.isi??? 86
social impact