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

Imagem de Miniatura
Arquivos
art_BATISTA_Trp28ArgIle35Thr_LHB_gene_variants_are_associated_with_elevated_2014.PDF (255.28 KB)
Citações na Scopus
10
Tipo de produção
article
Data de publicação
2014
DOI
Scopus
Web of Science
Título da Revista
ISSN da Revista
Título do Volume
Editora
ELSEVIER SCIENCE BV
Autores
BATISTA, Mariani Carla Prudente
DUARTE, Eliane de Fatima
BORBA, Michele Delarmelina dos Reis
ZINGLER, Emilie
MANGUSSI-GOMES, Joao
SANTOS, Beatriz Taynara Araujo dos
MORAES, Olivia Laquis de
NEVES, Francisco de Assis da Rocha
Citação
GENE, v.550, n.1, p.68-73, 2014
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
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: rsl 800447/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.
Palavras-chave
Polycystic ovary syndrome, LHB gene, Gene polymorphism, Hyperandrogenemia, Hirsutism
URI
https://observatorio.fm.usp.br/handle/OPI/8508
Referências
  1. Alexander Carolyn J, 2009, Rev Obstet Gynecol, V2, P232
  2. Ates S, 2013, GYNECOL ENDOCRINOL, V29, P931, DOI 10.3109/09513590.2013.819082
  3. Azziz R, 2004, J CLIN ENDOCR METAB, V89, P2745, DOI 10.1210/jc.2003-032046
  4. Chen ZJ, 2011, NAT GENET, V43, P55, DOI 10.1038/ng.732
  5. Dasgupta S, 2012, GENE, V494, P51, DOI 10.1016/j.gene.2011.11.054
  6. Elter K, 1999, FERTIL STERIL, V71, P425, DOI 10.1016/S0015-0282(98)00491-9
  7. HAAVISTO AM, 1995, J CLIN ENDOCR METAB, V80, P1257, DOI 10.1210/jc.80.4.1257
  8. Hayes FJ, 1998, J CLIN ENDOCR METAB, V83, P2343, DOI 10.1210/jc.83.7.2343
  9. Jakimiuk AJ, 2001, J CLIN ENDOCR METAB, V86, P1318, DOI 10.1210/jc.86.3.1318
  10. Kim NK, 2001, FERTIL STERIL, V75, P1238, DOI 10.1016/S0015-0282(01)01806-4
  11. Kosova G., 2013, MOL CELL ENDOCRINOL, V373, P28
  12. Lin LH, 2013, INT J GYNECOL OBSTET, V120, P115, DOI 10.1016/j.ijgo.2012.08.016
  13. Liu NN, 2012, REPROD BIOL ENDOCRIN, V10, DOI 10.1186/1477-7827-10-36
  14. LOBO RA, 1985, CLIN OBSTET GYNAECOL, V12, P633
  15. Lobo RA, 2000, ANN INTERN MED, V132, P989
  16. Lofrano-Porto A, 2007, NEW ENGL J MED, V357, P897, DOI 10.1056/NEJMoa071999
  17. MATTERI RK, 1989, AM J OBSTET GYNECOL, V161, P1704
  18. Mueller A, 2007, HORM RES, V67, P35, DOI 10.1159/000096036
  19. Nilsson C, 1997, FERTIL STERIL, V67, P998, DOI 10.1016/S0015-0282(97)81430-6
  20. Pau C, 2013, FERTIL STERIL, V99, P1774, DOI 10.1016/j.fertnstert.2012.12.033
  21. RAJKHOWA M, 1995, CLIN ENDOCRINOL, V43, P297, DOI 10.1111/j.1365-2265.1995.tb02035.x
  22. Ramanujam LN, 1999, CLIN ENDOCRINOL, V51, P243, DOI 10.1046/j.1365-2265.1999.00791.x
  23. Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group, 2004, HUM REPROD, V19, P41
  24. Ryckman K., 2008, CURR PROTOC HUM GENE, V57
  25. Segars JH, 2010, J CLIN ENDOCR METAB, V95, P2058, DOI 10.1210/jc.2010-0518
  26. Skrgatic L, 2012, J STEROID BIOCHEM, V128, P107, DOI 10.1016/j.jsbmb.2011.11.006
  27. Suganuma N, 1996, ENDOCRINOLOGY, V137, P831, DOI 10.1210/en.137.3.831
  28. Takahashi K, 1998, HUM REPROD, V13, P3338, DOI 10.1093/humrep/13.12.3338
  29. Takahashi K, 1999, FERTIL STERIL, V71, P96, DOI 10.1016/S0015-0282(98)00409-9
  30. Tapanainen JS, 1999, J CLIN ENDOCR METAB, V84, P1711, DOI 10.1210/jc.84.5.1711
  31. Urbanek M, 2007, NAT CLIN PRACT ENDOC, V3, P103, DOI 10.1038/ncpendmet0400
  32. Vink JM, 2006, J CLIN ENDOCR METAB, V91, P2100, DOI 10.1210/jc.2005-1494
  33. WALSH PS, 1991, BIOTECHNIQUES, V10, P506
  34. Wang R, 2012, MOL HUM REPROD, V18, P498, DOI 10.1093/molehr/gas024
  35. Xu N, 2010, FERTIL STERIL, V94, P781, DOI 10.1016/j.fertnstert.2009.10.020

Coleções
Artigos e Materiais de Revistas Científicas - FM/MOG
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - LIM/42
Artigos e Materiais de Revistas Científicas - LIM/58