Tetra primer ARMS-PCR relates folate/homocysteine pathway genes and ACE gene polymorphism with coronary artery disease

Abstract

Cardiovascular disorders and coronary artery disease (CAD) are significant contributors to morbidity and mortality in heart patients. As genes of the folate/homocysteine pathway have been linked with the vascular disease, we investigated association of these gene polymorphisms with CAD/myocardial infarction (MI) using the novel approach of tetraprimer ARMS-PCR. A total of 230 participants (129 MI cases, 101 normal subjects) were recruited. We genotyped rs1801133 and rs1801131 SNPs in 5'10' methylenetetrahydrofolate reductase (MTHFR), rs1805087 SNP in 5' methyltetrahydrofolate homocysteine methyltransferase (MTR), rs662 SNP in paroxanse1 (PON1), and rs5742905 polymorphism in cystathionine beta synthase (CBS). Angiotensin converting enzyme (ACE) insertion/deletion polymorphism was detected through conventional PCR. Covariates included blood pressure, fasting blood sugar, serum cholesterol, and creatinine concentrations. Our results showed allele frequencies at rs1801133, rs1801131, rs1805087 and the ACE insertion/deletion (I/D) polymorphism varied between cases and controls. Logistic regression, after adjusting for covariates, demonstrated significant associations of rs1801133 and rs1805087 with CAD in the additive, dominant, and genotype model. In contrast, ACE I/D polymorphism was significantly related with CAD where recessive model was applied. Gene-gene interaction against the disease status revealed two polymorphism groups: rs1801133, rs662, and rs1805087; and rs1801131, rs662, and ACE I/D. Only the latter interaction maintained significance after adjusted for covariates. Our study concludes that folate pathway variants exert contributory influence on susceptibility to CAD. We further suggest that tetraprimer ARMS-PCR successfully resolves the genotypes in selected samples and might prove to be a superior technique compared to the conventional approach.

OLR1,PON1andMTHFRGene Polymorphisms, Conventional Risk Factors and the Severity of Coronary Atherosclerosis in a Chinese Han Population

“…In previous studies, synergistic interactions between a gene and environment were also found [32,33,34]. In 2011, a case control study found that there was significant interaction between gene and conventional risk factors such as smoking or hypertension [34]. Our results suggest that polymorphisms do not act in isolation, but rather that the risk they confer can be increased by the presence of other polymorphisms or environmental factors.…”

“…Additionally, we identified a synergistic interaction between rs854563 and diabetes. In previous studies, synergistic interactions between a gene and environment were also found [32,33,34]. In 2011, a case control study found that there was significant interaction between gene and conventional risk factors such as smoking or hypertension [34].…”

Association between angiotensin-converting enzyme insertion/deletion polymorphisms and the risk of heart disease: an updated meta-analysis

“…From our subgroup analyses based on disease type, we found that all three subgroups (CHD, CAD, and MI) show an association between the DD genotype of ACE and high HD risk. These findings are in good accordance with multiple studies conducted previously (Bautista et al, 2004;Pulla Reddy et al, 2010;Sobti et al, 2010;Masud and Qureshi, 2011;Chen et al, 2013). The exception found in the American subgroup is most likely due to limited sample size.…”

“…Among these genetic factors, the roles of neurohormones have been extensively studied. For example, angiotensin-converting enzyme (ACE) has been proposed to play important roles in the progression of HDs (Bautista et al, 2004;Masud and Qureshi, 2011;Chen et al, 2013).…”

Role of homocysteinylation of ACE in endothelial dysfunction of arteries

“…Not only does Hcy itself have prooxidant properties, but also accumulating evidence from clinical and basic science studies indicate that the primary pathogenesis of diseases associated with HHcy is a concomitant generation of superoxide anion, which inactivates NO (7,27,28,51,56,58). To date, several studies have suggested the existence of an interaction between Hcy and angiotensin II (ANG II) signaling as a pathway that contributes significantly to the potential oxidative stress in the vasculature (2,31). Some studies have addressed the possibility of ANG II signaling-related proteins, such as angiotensinconverting enzyme (ACE), serving as a target of Hcy (4,30,34).…”