Association between the C242T polymorphism in the p22phox gene with arterial stiffness in the Brazilian population

Author(s)

Alvim, Rafael de Oliveira ^[1] ; Junior Lima Santos, Paulo Caleb ^[1] ; Dias, Rodrigo Goncalves ^[1] ; Rodrigues, Mariliza Velho ^[1] ; Cunha, Roberto de Sa ^[2] ; Mill, Jose Geraldo ^[2] ; Nadruz Junior, Wilson ^[3] ; Krieger, Jose Eduardo ^[1] ; Pereira, Alexandre Costa ^[1]

Affiliation

^[1] Univ Sao Paulo, Sch Med, Lab Genet & Mol Cardiol, Heart Inst InCor, BR-05403000 Sao Paulo - Brazil

^[2] Univ Fed Espirito Santo, Dept Physiol, Vitoria, ES - Spain

^[3] Univ Estadual Campinas, Fac Ciencias Med, Dept Clin Med, Sao Paulo - Brazil

• Document type: Journal article
• Source: Physiological Genomics; v. 44, n. 10, p. 587-592, MAY 2012.
• Web of Science Citations: 9

Abstract

de Oliveira Alvim R, Lima Santos PCJ, Goncalves Dias R, Rodrigues MV, de Sa Cunha R, Mill JG, Junior WN, Krieger JE, Pereira AC. Association between the C242T polymorphism in the p22phox gene with arterial stiffness in the Brazilian population. Physiol Genomics 44: 587-592, 2012. First published April 10, 2012; doi:10.1152/physiolgenomics.00122.2011.-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-alpha 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-alpha 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. (AU)

• FAPESP's process: 01/00009-0 - An integrated approach for the dissection of primary hypertension: molecular and functional characterization of the cardiovascular system
• Grantee: Eduardo Moacyr Krieger
• Support Opportunities: Research Projects - Thematic Grants