Avaliação de polimorfismos nos genes BMP6 e VDR na susceptibilidade à osteonecrose em pacientes com doença falciforme

• Main Author: SOUZA, Mariana Barros Souto de
• Other Authors: http://lattes.cnpq.br/3946903637397489
• Language: Portuguese
• Published: Universidade Federal de Pernambuco 2018
• Subjects: Polimorfismo (Genética); Genes; Osteonecrose
• Online Access: https://repositorio.ufpe.br/handle/123456789/25085

Submitted by Fernanda Rodrigues de Lima ([e-mail]) on 2018-07-12T20:00:24Z No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) DISSERTAÇÃO Mariana Barros Souto Souza.pdf: 2334625 bytes, checksum: a0fef77124581c4602c777533df38447 (MD5) === Approved for entry into archive by Alice Araujo ([e-mail]) on 2018-07-18T17:19:44Z (GMT) No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) DISSERTAÇÃO Mariana Barros Souto Souza.pdf: 2334625 bytes, checksum: a0fef77124581c4602c777533df38447 (MD5) === Made available in DSpace on 2018-07-18T17:19:45Z (GMT). No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) DISSERTAÇÃO Mariana Barros Souto Souza.pdf: 2334625 bytes, checksum: a0fef77124581c4602c777533df38447 (MD5) Previous issue date: 2017-02-23 === CNPQ === A osteonecrose é uma complicação crônica e progressiva da doença falciforme (DF) e ocorre devido à vaso-oclusão na microcirculação óssea, com infarto das superfícies articulares. Sabendo que a ocorrência da osteonecrose possui uma base multifatorial, polimorfismos de diversos genes, dentre eles o BMP6 e o VDR, têm sido bastante estudados. Pois participam diretamente do metabolismo ósseo. Assim o objetivo do nosso trabalho foi avaliar se existe associação entre polimorfismos nos genes BMP6 e VDR com o desenvolvimento da osteonecrose nos pacientes com DF. O estudo foi conduzido por comparação de grupos numa amostra de 303 pacientes com DF, divididos em 105 casos (83 HbSS, 11 HbSC, 11 HbSβ), os pacientes com osteonecrose e 198 controles (114 HbSS, 51 HbSC e 33 HbSβ) pacientes acima de 18 anos e que não apresentaram manifestações clínicas. Foram selecionados seis polimorfismos do BMP6 (rs3812163, rs270393, rs1225934, rs449853, rs267196, rs267201) e dois do VDR (FokI e Cdx2). A genotipagem dos polimorfismos foi realizada por PCR em tempo real utilizando sondas TaqMan®. Apenas os rs3812163 (T>A) e rs267201 (A>G) do BMP6 mostraram-se associados ao desenvolvimento de osteonecrose (P<0,0001). Juntamente com o FokI (P= 0,024) e com o Cdx2 (P= 0,046), aparecem como fatores de proteção contra o desenvolvimento da osteonecrose. A compreensão desses fatores de risco genéticos para o desenvolvimento da osteonecrose torna-se necessária para fornecer novos conhecimentos sobre a patogênese desta doença e, oferecer oportunidades para seu tratamento, que atualmente é limitado. === Osteonecrosis is a chronic and progressive complication of sickle cell disease (SCD) and occurs due to vaso-occlusion in the bone microcirculation, with infarction of the articular surfaces. Knowing that the occurrence of osteonecrosis has a multifactorial basis, polymorphisms of several genes, among them BMP6 and VDR, have been well studied. Because they participate directly in bone metabolism. Thus the objective of our study was to evaluate if there is an association between polymorphisms in BMP6 and VDR genes with the development of osteonecrosis in patients with SCD. The study was conducted by comparing a sample group of 303 patients with SCD divided in 105 cases (83 HBSS 11 HbSC, 11 HbSβ), patients with osteonecrosis and 198 controls (114 HBSS HbSC 51 and 33 HbSβ), patients over 18 years of age and who did not present clinical manifestations. Six BMP6 polymorphisms (rs3812163, rs270393, rs1225934, rs449853, rs267196, rs267201) and two within VDR (FokI and Cdx2) were selected. Polymorphism genotyping was performed by real-time PCR using TaqMan®. Only rs3812163 (T> A) and rs267201 (A> G) of BMP6 were shown to be associated with the development of osteonecrosis (P <0.0001). Together with FokI (P = 0.024) and Cdx2 (P = 0.046), they appear as protective factors against the development of osteonecrosis. Understanding these genetic risk factors for the development of osteonecrosis becomes necessary to provide new insights into the pathogenesis of this disease and provide opportunities for its treatment, which is currently limited.