title: Trp28Arg/Ile35Thr LHB gene variants are associated with elevated testosterone levels in women with polycystic ovary syndrome.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.affiliation: 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.
authors.forename: Mariani Carla Prudente
authors.initials: MC
authors.lastname: Batista
authors.affiliation: Departmento de Psiquiatria, HUB, UnB, Brazil; Department of Family Medicine, McGill University, Montreal, Canada.
authors.forename: Eliane de Fatima
authors.initials: Ede F
authors.lastname: Duarte
authors.affiliation: Ambulatório de Endocrinologia das Gônadas e Adrenais, Unidade de Endocrinologia, Hospital Universitário de Brasília (HUB), Universidade de Brasília (UnB), Brazil.
authors.forename: Michele Delarmelina dos Reis
authors.initials: MD
authors.lastname: Borba
authors.affiliation: 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.
authors.forename: Emilie
authors.initials: E
authors.lastname: Zingler
authors.affiliation: Ambulatório de Endocrinologia das Gônadas e Adrenais, Unidade de Endocrinologia, Hospital Universitário de Brasília (HUB), Universidade de Brasília (UnB), Brazil.
authors.forename: João
authors.initials: J
authors.lastname: Mangussi-Gomes
authors.affiliation: Laboratório de Farmacologia Molecular, Faculdade de Ciências da Saúde, UnB, Brazil.
authors.forename: Beatriz Taynara Araújo
authors.initials: BT
authors.lastname: dos Santos
authors.affiliation: Laboratório de Farmacologia Molecular, Faculdade de Ciências da Saúde, UnB, Brazil.
authors.forename: Olivia Laquis
authors.initials: OL
authors.lastname: de Moraes
authors.affiliation: Disciplina de Ginecologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil.
authors.forename: Sylvia Asaka Yamashita
authors.initials: SA
authors.lastname: Hayashida
authors.affiliation: Disciplina de Ginecologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil.
authors.forename: Edmund C
authors.initials: EC
authors.lastname: Baracat
authors.affiliation: Laboratório de Farmacologia Molecular, Faculdade de Ciências da Saúde, UnB, Brazil.
authors.forename: Francisco de Assis
authors.initials: Fde A
authors.lastname: da Rocha Neves
authors.affiliation: Disciplina de Ginecologia, Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, Brazil.
authors.forename: Gustavo Arantes Rosa
authors.initials: GA
authors.lastname: Maciel
authors.affiliation: Laboratório de Hormônios e Genética Molecular - LIM 42, FMUSP, Brazil.
authors.forename: Tania Aparecida Sartori Sanchez
authors.initials: TA
authors.lastname: Bachega
authors.affiliation: Unidade de Biologia Molecular, Laboratório e Instituto Sabin, Brasilia, DF, Brazil.
authors.forename: Gustavo Barcelos
authors.initials: GB
authors.lastname: Barra
authors.affiliation: 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.
authors.forename: Adriana
authors.initials: A
authors.lastname: Lofrano-Porto
mesh_terms: D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution; D000735:Androstenedione / Q000097:blood; D001938:Brazil; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D037101:Luteinizing Hormone, beta Subunit / Q000097:blood / Q000235:genetics*; D011085:Polycystic Ovary Syndrome / Q000097:blood* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D013739:Testosterone / Q000097:blood*; D055815:Young Adult
chemical_list: D037101:Luteinizing Hormone, beta Subunit; D013739:Testosterone; D000735:Androstenedione; D019314:Dehydroepiandrosterone Sulfate
keywords: Gene polymorphism; Hirsutism; Hyperandrogenemia; LHB gene; Polycystic ovary syndrome