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Analysis of polymorphisms of genes responsible for the biosynthesis and metabolism of collagen as risk factors for development of genital prolapse

Grant number: 14/01107-6
Support Opportunities:Regular Research Grants
Duration: March 01, 2015 - February 28, 2018
Field of knowledge:Health Sciences - Medicine - Maternal and Child Health
Principal Investigator:Emerson de Oliveira
Grantee:Emerson de Oliveira
Host Institution: Faculdade de Medicina do ABC (FMABC). Organização Social de Saúde. Fundação do ABC. Santo André , SP, Brazil
Associated researchers: César Eduardo Fernandes ; Ricardo Peres Do Souto


It is defined as genital prolapse the displacement of the pelvic viscera caudally toward the genital hiatus. Stems from the imbalance between the forces responsible for maintaining the pelvic organs in their normal position , and those that tend to propel them out of the pelvis. Several studies have linked the decreased amount of collagen with genital prolapse. Women with connective tissue diseases such as Marfan syndrome or Ehlers - Danlos syndrome have high rates of the disease .Vaginal fascia and ligaments have a predominance of collagen type I and III, which allow the accommodation of structures in cases of sudden increase in abdominal pressure and the passage of a fetus, for example. The genetic markers are polymorphisms that occur when a locus has two or more alleles, whose frequencies exceed 1% in the population. The single nucleotide polymorphism is a place where a single DNA base pair varies from person to person in a given population .It is believed that in humans there is more than one million polymorphisms , and of those, about 30,000 have phenotypic manifestations with clinical significance .Type I collagen is a component of connective tissue more closely related , studies , urinary incontinence and pelvic organ prolapse. This protein is composed of three peptide chains : two ± 1 and ± 2 (± 1 () 2 ± 2 (?) ? '), Synthesized by the COL1A1 and COL1A2 genes, respectively ( ? ) ( ? ) . Studies have shown that the single base polymorphism ( SNP ) G ? T Sp1 site located in the first intron of COL1A1 ( rs1800012 ) gene affects transcriptional regulation of collagen .Mutations affecting COL1A2 gene reduce the biosynthesis of collagen type I. However, the clinical status of patients is quite different .The type III collagen minors and thin , responsible for the flexibility and elasticity of the tissue fibers . It is found in skin, aorta , lungs , uterus , fascia and ligaments . It is a heterotrimeric protein composed of two chains and a chain -1 ± ± -2 . These chains have similar spatial structure, but are encoded by different genes. The gene encoding the chain ± -1 is called COL3A1 and is located on chromosome 2q24.3 - q31 , should be coordinated and tightly controlled to form a proper protein structure. Recently some studies have attempted to relate the polymorphism of this gene with genital prolapse.The matrix metalloproteinases (MMPs ) are a family of proteolytic enzymes that degrade extracellular matrix components such as collagen , gelatin and elastin. The vertebrate MMPs act on various substrates , and are able to degrade virtually all components of the extracellular matrix.MMP -1 plays an important role in the degradation of type I collagen , whereas MMP -3 can activate other MMPs including MMP- 1. That said , it is plausible to believe that the overexpression of these enzymes could in part explain the increased susceptibility to the development of pelvic organ prolapse.LOX is traditionally recognized for exercising the function of catalyzing lysine -derived cross- linkages and hidroxilisinas on collagen fibers , and lysine in elastin fibers . Dysfunctions in the LOX gene lead to a reduction in the interconnections of the fibers, suggesting the involvement of the enzyme in the maturation and stabilization of collagen and elastin fibers process.Accurate identification of patients at increased risk for developing genital prolapse would be revolutionary in the sense preventive and treatment of disease.We proposed , in this study , to assess whether the polymorphisms of genes of the biosynthesis and metabolism of collagen ( COL1A1 , COL1A2 , COL3A1 , MMP1 , MMP3 , MMP9 , and LOXL1 ) are risk factors for the development of pelvic organ prolapse. (AU)

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Scientific publications (5)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
GHERSEL, FREDERICO REZENDE; SOUTO, RICARDO PERES; PACHECO GONZALES, ESTER WILMA; PAULO, DENISE SOUZA; EDUARDO FERNANDES, CESAR; OLIVEIRA, EMERSON. Avaliação de polimorfismos de genes de matriz de metaloproteinase 9 (MMP9) como fatores de risco para o prolapso de órgãos pélvicos na população brasileira. Revista Brasileira de Ginecologia e Obstetrícia, v. 41, n. 3, p. 164-169, . (14/01107-6)
TEIXEIRA, FERNANDO HENRIQUE; FERNANDES, CESAR EDUARDO; SOUTO, RICARDO PERES; DE OLIVEIRA, EMERSON. Polymorphism rs1800255 from COL3A1 gene and the risk for pelvic organ prolapse. INTERNATIONAL UROGYNECOLOGY JOURNAL, v. 31, n. 1, p. 73-78, . (14/01107-6)
DE FREITAS ROSA, JOSYANDRA PAULA; HADDAD, RAPHAEL FEDERICCI; REIS MAEDA, FABIANA GARCIA; SOUTO, RICARDO PERES; FERNANDES, CESAR EDUARDO; DE OLIVEIRA, EMERSON. Associação entre polimorfismo do gene col1a2 e a ocorrência do prolapso de órgãos pélvicos em mulheres brasileiras. Revista Brasileira de Ginecologia e Obstetrícia, v. 41, n. 1, p. 31-36, . (14/01107-6)
MARCUS VINICIUS BARBOSA DE PAULA; MARCOS ANTÔNIO DE FARIAS LIRA JÚNIOR; VIVIAN COSTA E SILVA CROCCO MONTEIRO; RICARDO PERES SOUTO; CÉSAR EDUARDO FERNANDES; EMERSON DE OLIVEIRA. Evaluation of the fibulin 5 gene polymorphism as a factor related to the occurrence of pelvic organ prolapse. Revista da Associação Médica Brasileira, v. 66, n. 5, p. 680-686, . (14/01107-6)

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