Angiotensin-converting enzyme and p22phox polymorphisms and the risk of coronary heart disease in a low-risk Spanish population

Abstract

OBJECTIVE:To evaluate the genetic contribution to myocardial infarction in a homogeneous Caucasian population (a Mediterranean Spanish population) with very low frequency of coronary heart disease (CHD). DESIGN:We analyzed a total of 210 subjects, younger than 55 years, considered to be a low-risk population (104 cases of myocardial infarction and 106 control), and genotyped them (using polymerase chain reaction and sequencing) for the angiotensin-converting enzyme (ACE) insertion/deletion (ACE I/D) and for the C242T polymorphism of NADPH oxidase p22(phox). Also, we sequenced 23 alleles of the ACE gene (9 D and 14 I) for the region that includes the end of the intron 16 and the exon 17. RESULTS:The ACE genotype-prevalence values for II, ID and DD were 4.81%, 28.85% and 66.34%, respectively, among the myocardial infarction patients, and 2.83%, 71.70% and 25.47% among controls. The statistical analysis comparing patients and controls revealed significant differences (chi(2)=25.09, P=0.00000055) between the two subpopulations. Also, we found a strong association between the genotype DD and the risk of suffering CHD (odds ratio (OR): 3.64; 95% CI: 2.37-8.07). The prevalence of the CC, TC and TT genotypes of p22(phox) gene among healthy controls proved to be 53.77%, 44.34% and 1.89%, while those of myocardial infarction were 58.65%, 39.42% and 1.93%, respectively. The association of C242T polymorphism of the p22(phox) gene with CHD was not statistically significant, (chi(2)=0.49, P=0.48). Logisticregression analysis demonstrated that the independent risk factor for developing myocardial infarction was the DD genotype of ACE gene. Finally, our results indicate

NAD(P)H oxidase p22phox gene C242T polymorphism, nitric oxide production, salt sensitivity and cardiovascular risk factors in Hispanics

“…The frequency of the T allele described for healthy subjects is less common in Japanese (0.07-0.13) and Chinese (0.066) than in European and Australian Caucasians (0.23-0.31). [17][18][19][20][21][22] The frequency of the T allele in Venezuelans reported in this study was comparable to that previously described for Caucasians, as the T allele was found in 27% of the Venezuelan subjects studied (present study). These findings are consistent with previous observations, where the frequency of both the alpha adducin and the eNOS polymorphisms described for Venezuelans was comparable to that of Anglo-Saxons and Spanish Caucasians, and significantly different from that of Orientals and African-Americans.…”

“…However, clinical studies searching for the association of the polymorphism with cardiovascular diseases have provided contradictory results. Although the T allele appeared to confer cardiovascular risk protection in some studies, 16,17,20,[25][26][27] either no protection or increase risk was found in others. 15,17,21,22 In fact, the C242T polymorphism was found associated with coronary artery spasm, 15 coronary artery disease, 21 cerebrovascular disease and with atherothrombotic infarction.…”

The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology

“…3) Equal risk in His72Tyr carriers was described for cardiovascular disease or risk factors (123,287,484,533,586,812,827). One study also reports equal risk for cardiovascular risk factors, but increased salt sensitivity and decreased levels of nitric oxide metabolites in His72Tyr carriers (129).…”

Meta-analysis of C242T polymorphism in CYBA genes: risk of acute coronary syndrome is lower in Asians but not in Caucasians

“…One study (Katakami et al, 2009) was excluded since it was overlapped by another study with a larger scale (Katakami et al, 2010). Three publications did not meet the requirements of HWE (P HWE <0.05) (Mata-Balaguer et al, 2004;Morgan et al, 2007;Hashad et al, 2014). Finally, a total of 10 casecontrol studies were retrieved on ACS and the CYBA C242T polymorphism (Gardemann et al, 1999;Stanger et al, 2001;Yamada et al, 2002;Murase et al, 2004;Vasiliadou et al, 2006;Macías-Reyes et al, 2008;Katakami et al, 2010;de Caterina et al, 2011;Goliasch et al, 2011;Narne et al, 2012).…”