Mariani Carla Prudente Batista1, Eliane de Fatima Duarte2, Michele Delarmelina dos Reis Borba3, Emilie Zingler4, João Mangussi-Gomes3, Beatriz Taynara Araújo dos Santos5, Olivia Laquis de Moraes5, Sylvia Asaka Yamashita Hayashida6, Edmund C Baracat6, Francisco de Assis da Rocha Neves5, Gustavo Arantes Rosa Maciel6, Tania Aparecida Sartori Sanchez Bachega7, Gustavo Barcelos Barra8, Adriana Lofrano-Porto9. 1. 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. 2. Departmento de Psiquiatria, HUB, UnB, Brazil; Department of Family Medicine, McGill University, Montreal, Canada. 3. Ambulatório de Endocrinologia das Gônadas e Adrenais, Unidade de Endocrinologia, Hospital Universitário de Brasília (HUB), Universidade de Brasília (UnB), Brazil. 4. 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. 5. Laboratório de Farmacologia Molecular, Faculdade de Ciências da Saúde, UnB, Brazil. 6. Disciplina de Ginecologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil. 7. Laboratório de Hormônios e Genética Molecular - LIM 42, FMUSP, Brazil. 8. Unidade de Biologia Molecular, Laboratório e Instituto Sabin, Brasilia, DF, Brazil. 9. 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.
Abstract
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.
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.
Authors: Luis Eduardo Prado Correia; Bruna Cristine de Almeida; Manuel de Jesus Simões; Mauro Abi Haidar; Daniela Berguio Vidotti; Ivaldo Silva Journal: Biomed Res Int Date: 2017-12-21 Impact factor: 3.411
Authors: Alessandro Conforti; Frank Tüttelmann; Carlo Alviggi; Hermann M Behre; Robert Fischer; Liang Hu; Nikolaos P Polyzos; Dana Chuderland; Gottumukkala Achyuta Rama Raju; Thomas D'Hooghe; Manuela Simoni; Sesh K Sunkara; Salvatore Longobardi Journal: Front Endocrinol (Lausanne) Date: 2022-02-01 Impact factor: 5.555