Signaling pathway genes for blood pressure, folate and cholesterol levels among hypertensives: an epistasis analysis

Irregular atrial pressure, defective folate and cholesterol metabolism contribute to the pathogenesis of hypertension. however, little is known about the combined roles of the methylenetetrahydrofolate reductase (mthfr), apolipoprotein-e (apoe) and angiotensin-converting enzyme (ace) genes, which are involved in metabolism and homeostasis. the objective of this study is to investigate the association of the mthfr 677 c>t and 1298a>c, ace insertion–deletion (i/d) and apoe genetic polymorphisms with hypertension and to further explore the epistasis interactions that are involved in these mechanisms. a total of 594 subjects, including 348 normotensive and 246 hypertensive ischemic stroke subjects were recruited. the mthfr 677 c>t and 1298a>c, ace i/d and apoepolymorphisms were genotyped and the epistasis interaction were analyzed. the mthfr 677 c>t and apoe polymorphisms demonstrated significant associations with susceptibility to hypertension in multiple logistic regression models, multifactor dimensionality reduction and a classification and regression tree. in addition, the logistic regression model demonstrated that significant interactions between the apoe e3e3, e2e4, e2e2 and mthfr 677 c>t polymorphisms existed. in conclusion, the results of this epistasis study indicated significant association between the apoe and mthfr polymorphisms and hypertension.