Association of epistatic effects of MTHFR, ACE, APOB, and APOE gene polymorphisms with the risk of myocardial infarction and unstable angina in Egyptian patients

Showing the impact of gene-gene interactions and gene-environment interaction of MTHFR C677T and A1298C, ACE I/D, APOB R3500Q, and APOE ε4 polymorphisms on the risk of MI and UA in Egyptian patients. [Display omitted] •Epistatic effects of five polymorphisms in MTHFR, ACE, APOB and APOE may strongly...

Full description

Saved in:
Bibliographic Details
Published in:Gene 2024-02, Vol.895, p.147976-147976, Article 147976
Main Authors: Taha, Mohamed, Ibrahim, Mohamed Moussa Mohamed, Sedrak, Heba
Format: Article
Language:English
Subjects:
Acute coronary syndrome
Angina, Unstable
Apo B
Apo E
Apolipoproteins - genetics
Apolipoproteins B - genetics
Apolipoproteins E - genetics
Case-Control Studies
Coronary Artery Disease - genetics
Diabetes Mellitus
Egypt
Epistasis
Gene Frequency
Gene-environment interactions
Genetic Predisposition to Disease
Genotype
Humans
Methylenetetrahydrofolate Reductase (NADPH2) - genetics
Myocardial Infarction - genetics
Peptidyl-Dipeptidase A - genetics
Polymorphism, Genetic
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Showing the impact of gene-gene interactions and gene-environment interaction of MTHFR C677T and A1298C, ACE I/D, APOB R3500Q, and APOE ε4 polymorphisms on the risk of MI and UA in Egyptian patients. [Display omitted] •Epistatic effects of five polymorphisms in MTHFR, ACE, APOB and APOE may strongly predict MI risk.•ACE I/D-R3500Q interaction posed a decreased risk of UA.•TCDGε3, CADGε4, and TADGε4-C677T-A1298C-ACE I/D-R3500Q-APOE haplotypes are strongly associated with MI risk.•CDG or CIG-C677T-ACE I/D-R3500Q haplotype was highly protective against UA risk.•Gene-environment interaction is seen between haplotypes and risk factors and clinical data in MI and UA patients. Despite remarkable discoveries in the genetic susceptibility of coronary artery disease (CAD), a large part of heritability awaits identification. Epistasis or gene‐gene interaction has a profound influence on CAD and might contribute to its missed genetic variability; however, this impact was largely unexplored. Here, we appraised the associations of gene-gene interactions and haplotypes of five polymorphisms, namely methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, angiotensin converting enzyme (ACE) insertion/deletion (I/D), apolipoprotein B (APOB) R3500Q, and apolipoprotein E (APOE) ε4 with the risk of myocardial infarction (MI) and unstable angina (UA). Gene-environment interactions with traditional risk factors and clinical data were also scrutinized. This study recruited 100 MI, 50 UA patients, and 100 apparently healthy controls. Logistic regression models were employed in association analyses. We remarked that the single locus effect of individual polymorphisms was relatively weak; however, a magnified effect of their combination via gene-gene interaction may predict MI risk after adjustment for multiple comparisons. Only MTHFR C677T, ACE I/D, and APOB R5300Q were associated with the risk of UA, and the ACE I/D-R3500Q interaction posed a decreased UA risk. APOB R3500Q was in strong linkage disequilibrium with MTHFR C677T, ACE I/D, and APE ε4 polymorphisms. The TCDGε3, CADGε4, and TADGε4-C677T-A1298C-ACE I/D-R3500Q-APOE haplotypes were associated with escalating MI risk, while the CDG or CIG-C677T-ACE I/D-R3500Q haplotype was highly protective against UA risk compared to controls. Interestingly, the CADGε4 and CAIGε3 haplotypes were strongly associated with the presence of diabetes and hypertension, respectively in MI patients; both haplotypes stratified patients accordi
ISSN:0378-1119
1879-0038
DOI:10.1016/j.gene.2023.147976