title: 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.
authors: 1] Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia [2] Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.
authors: L K
authors: LK
authors: Wei
authors: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.
authors: S
authors: S
authors: Menon
authors: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.
authors: L R
authors: LR
authors: Griffiths
authors: Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia.
authors: S H
authors: SH
authors: Gan
mesh_terms: D000328:Adult; D001057:Apolipoproteins E / Q000235:genetics*; D001794:Blood Pressure / Q000235:genetics; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood; D004843:Epistasis, Genetic; D005260:Female; D005492:Folic Acid / Q000097:blood; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000235:genetics*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D015398:Signal Transduction / Q000235:genetics
chemical_list: D001057:Apolipoproteins E; D005492:Folic Acid; D002784:Cholesterol; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D007703:Peptidyl-Dipeptidase A