Epistasis analysis of metabolic genes polymorphisms associated with ischemic heart disease in Yucatan

Abstract

ObjectiveEpistasis is a type of genetic interaction that could explain much of the phenotypic variability of complex diseases. In this work, the effect of epistasis of metabolic genes and cardiovascular risk on the susceptibility to the development of ischaemic heart disease in Yucatan was determined. MethodsCase–control study in 79 Yucatecan patients with ischaemic heart disease and 101 healthy controls matched by age and origin with cases. The polymorphisms -108CT, Q192R, L55 M (paraoxonase 1; PON1), C677T, A1298C (5,10-methylenetetrahydrofolate reductase; MTHFR), and the presence/absence of the glutathione S-transferase T1 (GSTT1) gene were genotyped. Epistasis analysis was performed using the multifactorial dimensional reduction method. The best risk prediction model was selected based on precision (%), statistical significance (p<0.05) and cross-validation consistency. ResultsWe found an independent association of the null genotype GSTT1*0/0 (OR=3.39; CI: 1.29–8.87; p=0.017) and the null allele (OR=1.86; CI: 1.19–2.91; p=0.007) with ischaemic heart disease. The GSTT1*0 deletion and the 677TT genotype (MTHFR) were identified as being at a high cardiovascular risk, whereas the GSTT1*1 wild type genotype and the CC677 variant were at low risk. The gene–environment interaction identified the GSTT1 gene, C677T polymorphism (MTHFR) and hypertension as the factors that best explain ischaemic heart disease in the study population. ConclusionsThe interaction of the GSTT1 and MTHFR and hypertension may constitute a predictive model of risk for early onset ischaemic heart disease in the population of Yucatan.