engleski

Epistatic interactions between the ACE, APOE, eNOS and MTHFR polymorphisms affect individual susceptibility to complex cardiovascular diseases in the Croatian oldest-olds

Genes whose products are involved in metabolism and homeostasis include angiotensin-I- converting enzyme gene (ACE), apolipoprotein-E gene (APOE), endothelial nitric oxide synthetase gene (eNOS) and methylenetetrahydrofolate reductase enzyme gene (MTHFR). They are extensively studied for their role in the development of cardiovascular diseases (CVDs), but little is known about their epistatic influence on CVD phenotypes, particularly in senescence. In this study we investigated the epistatic interactions of the ACE (I/D), ApoE (ε), eNOS VNTR (4, 5) and MTHFR (C677T) genetic polymorphisms with several CVD phenotypes in oldest-olds from Zagreb, Croatia (N=320 ; 85-101 yrs ; mean=88.32 yrs ; 82 M/238 F). The genotypes of four mentioned polymorphisms were determined using RFLP and multiplex PCR. After adjusting for age, sex, BMI, glucose and cholesterol levels, the logistic regression analysis results showed that carriers of both APOE ε2ε3 and MTHFR CT were at greater risk for hypertension (odds ratio [OR] 5.829 ; 95% confidence interval [CI] 1.314-25.867 ; p < 0.05). Obesity was found significantly more often in ACE I-allele carriers who were at the same time eNOS VNTR 44 or 55 homozygotes (OR 2.021 ; CI 1.156-3.532 ; p<0.01), after adjusting for age, sex, blood pressure, triglyceride, glucose and cholesterol levels. CVD phenotypes (cerebrovascular insult, angina pectoris, myocardial infarction) were found less often in carriers of ACE DD, eNOS 55 and MTHFR TT genotypes (OR 0.099 ; CI 0.012- 0.797 ; p<0.05), after adjusting for age, sex, BMI and blood pressure. In conclusion, the results of this study indicated significant epistatic interactions between the studied polymorphisms relevant for CVD status in senescent individuals.

ACE (I/D) ; APOE (ε) ; eNOS VNTR (4/5) ; epistasis ; MTHFR (C667T) ; oldest-olds

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