Trp28Arg/Ile35Thr LHB gene variants are associated with elevated testosterone levels in women with polycystic ovary syndrome.

Autor: Batista MC; Ambulatório de Endocrinologia das Gônadas e Adrenais, Unidade de Endocrinologia, Hospital Universitário de Brasília (HUB), Universidade de Brasília (UnB), Brazil; Unidade de Endocrinologia, Hospital Regional de Taguatinga, Brasília, DF, Brazil., Duarte Ede F; Departmento de Psiquiatria, HUB, UnB, Brazil; Department of Family Medicine, McGill University, Montreal, Canada., Borba MD; Ambulatório de Endocrinologia das Gônadas e Adrenais, Unidade de Endocrinologia, Hospital Universitário de Brasília (HUB), Universidade de Brasília (UnB), Brazil., Zingler E; Ambulatório de Endocrinologia das Gônadas e Adrenais, Unidade de Endocrinologia, Hospital Universitário de Brasília (HUB), Universidade de Brasília (UnB), Brazil; Laboratório de Farmacologia Molecular, Faculdade de Ciências da Saúde, UnB, Brazil., Mangussi-Gomes J; Ambulatório de Endocrinologia das Gônadas e Adrenais, Unidade de Endocrinologia, Hospital Universitário de Brasília (HUB), Universidade de Brasília (UnB), Brazil., dos Santos BT; Laboratório de Farmacologia Molecular, Faculdade de Ciências da Saúde, UnB, Brazil., de Moraes OL; Laboratório de Farmacologia Molecular, Faculdade de Ciências da Saúde, UnB, Brazil., Hayashida SA; Disciplina de Ginecologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil., Baracat EC; Disciplina de Ginecologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil., da Rocha Neves Fde A; Laboratório de Farmacologia Molecular, Faculdade de Ciências da Saúde, UnB, Brazil., Maciel GA; Disciplina de Ginecologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil., Bachega TA; Laboratório de Hormônios e Genética Molecular - LIM 42, FMUSP, Brazil., Barra GB; Unidade de Biologia Molecular, Laboratório e Instituto Sabin, Brasilia, DF, Brazil., Lofrano-Porto A; Ambulatório de Endocrinologia das Gônadas e Adrenais, Unidade de Endocrinologia, Hospital Universitário de Brasília (HUB), Universidade de Brasília (UnB), Brazil; Laboratório de Farmacologia Molecular, Faculdade de Ciências da Saúde, UnB, Brazil. Electronic address: adlofrano@unb.br.
Jazyk: angličtina
Zdroj: Gene [Gene] 2014 Oct 15; Vol. 550 (1), pp. 68-73. Date of Electronic Publication: 2014 Aug 08.
DOI: 10.1016/j.gene.2014.08.017
Abstrakt: Introduction: Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder, of multifactorial etiology, which affects 6-10% of women of reproductive age. It is considered the leading cause of anovulatory infertility, menstrual disorders and hyperandrogenism in this population. The genetic basis of PCOS is still largely unknown despite significant family clustering; determining its mode of inheritance is particularly difficult given the heterogenic presentation of the disease.
Materials and Methods: 130 Brazilian women, aged 14-42 years, who met the 2003 Rotterdam criteria for PCOS diagnosis, were included, and 96 healthy women constituted the control group. Presence of hirsutism was classified using the modified Ferriman-Gallwey score (F-G score) as absent (≤7), mild (8-14), and severe (≥15). Blood levels of luteinizing hormone (LH), total testosterone (TT), dehydroepiandrosterone sulfate (DHEA-S) and androstenedione were determined. The coding region of the luteinizing hormone beta-subunit (LHB) gene was amplified and sequenced. Differences in allelic and genotypic frequency distribution of each polymorphism across controls and cases were estimated by the Mantel-Haenszel chi-square or Fisher's exact test (p<0.05), and the probability of an association between the detection of a polymorphism and presence of a diagnosis of PCOS, by logistic regression.
Result(s): Sequencing detected 8 polymorphisms in the LHB gene coding region. Two polymorphisms in linkage disequilibrium were significantly more prevalent in the presence of hyperandrogenemia: rs1800447/rs34349826 (Trp28Arg/Ile35Thr) (p=0.02).
Conclusion(s): In this series, a modulatory effect of LHB polymorphisms on hyperandrogenemia phenotype of PCOS was observed; however, this finding needs to be replicated in other populations.
(Copyright © 2014 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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