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Association between the C242T polymorphism in the p22phox gene with arterial stiffness in the Brazilian population.
de Oliveira Alvim, Rafael; Santos, Paulo Caleb Junior Lima; Dias, Rodrigo Gonçalves; Rodrigues, Mariliza Velho; de Sa Cunha, Roberto; Mill, José Geraldo; Junior, Wilson Nadruz; Krieger, José Eduardo; Pereira, Alexandre Costa.
Afiliação
  • de Oliveira Alvim R; Laboratory of Genetics and Molecular Cardiology, Heart Institute-InCor, University of Sao Paulo Medical School, Sao Paulo, Brazil.
Physiol Genomics ; 44(10): 587-92, 2012 May 01.
Article em En | MEDLINE | ID: mdl-22496489
NADPH oxidase p22phox subunit is responsible for the production of reactive oxygen species in the vascular tissue. The C242T polymorphism in the p22phox gene has been associated with diverse coronary artery disease phenotypes, but the findings about the protective or harmful effects of the T allele are still controversial. Our main aim was to assess the effect of p22phox C242T genotypes on arterial stiffness, a predictor of late morbidity and mortality, in individuals from the general population. We randomly selected 1,178 individuals from the general population of Vitoria City, Brazil. Genotypes for the C242T polymorphism were detected by PCR-RFLP, and pulse wave velocity (PWV) values were measured with a noninvasive automatic device Complior. p22phox and TNF-α gene expression were quantified by real-time PCR in human arterial mammary smooth muscle cells. In both the entire and nonhypertensive groups: individuals carrying the TT genotype had higher PWV values and higher risk for increased arterial stiffness [odds ratio (OR) 1.93, 95% confidence interval (CI) 1.27-2.92 and OR 1.78, 95% CI 1.07-2.95, respectively] compared with individuals carrying CC+CT genotypes, even after adjustment for covariates. No difference in the p22phox gene expression according C242T genotypes was observed. However, TNF-α gene expression was higher in cells from individual carrying the T allele, suggesting that this genetic marker is associated with functional phenotypes at the gene expression level. In conclusion, we suggest that p22phox C242T polymorphism is associated with arterial stiffness evaluated by PWV in the general population. This genetic association shed light on the understanding of the genetic modulation on vascular dysfunction mediated by NADPH oxidase.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Polimorfismo Genético / Fator de Necrose Tumoral alfa / NADPH Oxidases / Rigidez Vascular Tipo de estudo: Observational_studies / Prevalence_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Female / Humans / Male / Middle aged País/Região como assunto: America do sul / Brasil Idioma: En Revista: Physiol Genomics Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2012 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Polimorfismo Genético / Fator de Necrose Tumoral alfa / NADPH Oxidases / Rigidez Vascular Tipo de estudo: Observational_studies / Prevalence_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Female / Humans / Male / Middle aged País/Região como assunto: America do sul / Brasil Idioma: En Revista: Physiol Genomics Assunto da revista: BIOLOGIA MOLECULAR Ano de publicação: 2012 Tipo de documento: Article País de afiliação: Brasil País de publicação: Estados Unidos