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

Abstract

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.

The effect of APOE, CETP, and PCSK9 polymorphisms on simvastatin response in Thai hypercholesterolemic patients

“…The mechanism of APOE that influences lipid levels after statin therapy may be due to the affinity binding to low‐density lipoprotein receptors (LDLR). It has been reported that APOE2 has markedly decreased binding affinity to LDLR of less than 2% of normal binding as compared to APOE3 …”

“…It has been reported that APOE2 has markedly decreased binding affinity to LDLR of less than 2% of normal binding as compared to APOE3. 37,38 Thus, it subsequently decreased the hepatic cholesterol and resulted in the up-regulation of HMG CoA reductase activity and LDLR, 37 whereas APOE4 increased the affinity to LDLR when compared with APOE3 39 and thus it accelerates the clearance of apoB100and apoE-containing lipoproteins resulting in increased hepatocellular cholesterol and suppression of HMG CoA reductase activity. This may in turn lead to the down-regulation of LDLR and increased LDL-C levels.…”

Clinical Relevance of MTHFR, eNOS, ACE, and ApoE Gene Polymorphisms and Serum Vitamin Profile among Malay Patients with Ischemic Stroke

“…8 The ACE gene, which encodes for angiotensin converting enzyme, is a potent regulator in reninangiotensin system where the ACE I/D accounts for approximately half of the phenotypic variance in serum ACE levels and contributes to hypertension. 4,9 There has been mounting evidence which suggests that the E2, E3 and E4 polymorphisms of ApoE play a key role in lipid metabolism and hypercholesterolemia. 4 The purpose of this study was threefold.…”

Studying the association between methylenetetrahydrofolate reductase (MTHFR) 677 gene polymorphism, cardiovascular risk and lichen planus

“…The association between MTHFR 677 C>T polymorphism with susceptibility to hypertension has been previously demonstrated. 27 An increase in Hcy and the risk of CVD in patients with MTHFR mutation has been also previously reported. 28 As a conclusion, MTHFR 677 gene polymorphism may be a risk factor for the development of LP and to predispose these patients with hyperhomocysteinemia or any other features of high cardiovascular risk.…”

“…This finding could highlight the possible higher association between TT and CT mutant genotypes and cardiovascular risk. The association between MTHFR 677 C>T polymorphism with susceptibility to hypertension has been previously demonstrated . An increase in Hcy and the risk of CVD in patients with MTHFR mutation has been also previously reported …”