Reproductive physiology in young men is cumulatively affected by FSH-action modulating genetic variants : FSHR -29G/A and c.2039 A/G, FSHB -211G/T

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dc.contributor.authorGrigorova, Marina
dc.contributor.authorPunab, Margus
dc.contributor.authorPunab, Anna Maria
dc.contributor.authorPoolamets, Olev
dc.contributor.authorVihljajev, Vladimir
dc.contributor.authorŽilaitiene, Birute
dc.contributor.authorErenpreiss, Juris
dc.contributor.authorMatulevičius, Valentinas
dc.contributor.authorLaan, Maris
dc.contributor.institutionScientific Laboratory of Molecular Genetics
dc.date.accessioned2021-08-19T07:45:01Z
dc.date.available2021-08-19T07:45:01Z
dc.date.issued2014-04-09
dc.description.abstractFollicle-Stimulating Hormone Receptor (FSHR) -29G/A polymorphism (rs1394205) was reported to modulate gene expression and reproductive parameters in women, but data in men is limited. We aimed to bring evidence to the effect of FSHR -29G/A variants in men. In Baltic young male cohort (n = 982; Estonians, Latvians, Lithuanians; aged -0.2±2.0 years), the FSHR -29 A-allele was significantly associated with higher serum FSH (linear regression: effect 0.27 IU/L; P = 0.0019, resistant to Bonferroni correction for multiple testing) and showed a non-significant trend for association with higher LH (0.19 IU/L) and total testosterone (0.93 nmol/L), but reduced Inhibin B (-7.84 pg/mL) and total testes volume (effect -1.00 mL). Next, we extended the study and tested the effect of FSHR gene haplotypes determined by the allelic combination of FSHR -29G/A and a well-studied variant c.2039 A/G (Asn680Ser, exon 10). Among the FSHR -29A/2039G haplotype carriers (A-Ser; haplotype-based linear regression), this genetic effect was enhanced for FSH (effect 0.40 IU/L), Inhibin B (-16.57 pg/mL) and total testes volume (-2.34 mL). Finally, we estimated the total contribution of three known FSH-action modulating SNPs ( FSHB -211G/T; FSHR -29G/A, c.2039 A/G) to phenotypic variance in reproductive parameters among young men. The major FSH-action modulating SNPs explained together 2.3%, 1.4%, 1.0 and 1.1% of the measured variance in serum FSH, Inhibin B, testosterone and total testes volume, respectively. In contrast to the young male cohort, neither FSHR -29G/A nor FSHR haplotypes appeared to systematically modulate the reproductive physiology of oligozoospermic idiopathic infertile patients (n = 641, Estonians; aged 31.5±6.0 years). In summary, this is the first study showing the significant effect of FSHR -29G/A on male serum FSH level. To account for the genetic effect of known common polymorphisms modulating FSH-action, we suggest haplotype-based analysis of FSHR SNPs (FSHR -29G/A, c.2039 A/G) in combination with FSHB -211G/T testing.en
dc.description.statusPeer reviewed
dc.format.extent735062
dc.identifier.citationGrigorova, M, Punab, M, Punab, A M, Poolamets, O, Vihljajev, V, Žilaitiene, B, Erenpreiss, J, Matulevičius, V & Laan, M 2014, 'Reproductive physiology in young men is cumulatively affected by FSH-action modulating genetic variants : FSHR -29G/A and c.2039 A/G, FSHB -211G/T', PLoS ONE, vol. 9, no. 4, e94244. https://doi.org/10.1371/journal.pone.0094244
dc.identifier.doi10.1371/journal.pone.0094244
dc.identifier.issn1932-6203
dc.identifier.urihttps://dspace.rsu.lv/jspui/handle/123456789/6042
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=84899567811&partnerID=8YFLogxK
dc.language.isoeng
dc.relation.ispartofPLoS ONE
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subject1.6 Biological sciences
dc.subject3.1 Basic medicine
dc.subject1.1. Scientific article indexed in Web of Science and/or Scopus database
dc.subjectGeneral Biochemistry,Genetics and Molecular Biology
dc.subjectGeneral Agricultural and Biological Sciences
dc.subjectGeneral
dc.titleReproductive physiology in young men is cumulatively affected by FSH-action modulating genetic variants : FSHR -29G/A and c.2039 A/G, FSHB -211G/Ten
dc.type/dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article

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