Genetic predisposition to left ventricular dysfunction: a multigenic and multi-analytical approach
| Autor: | Avshesh Mishra, Tulika Mittal, Balraj Mittal, Anshika Srivastava, Naveen Garg |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Male
medicine.medical_specialty MMP9 Biology Bioinformatics Receptor Angiotensin Type 1 Renin-Angiotensin System Coronary artery disease Ventricular Dysfunction Left Internal medicine Genetics medicine Genetic predisposition Humans Genetic Predisposition to Disease Aged Polymorphism Genetic Angiotensin II receptor type 1 Ejection fraction Genetic variants NF-kappa B p50 Subunit General Medicine Middle Aged medicine.disease medicine.anatomical_structure Matrix Metalloproteinase 9 Ventricle Matrix Metalloproteinase 7 Cardiology Female Inflammatory pathways |
| Zdroj: | Gene. 546:309-317 |
| ISSN: | 0378-1119 |
| DOI: | 10.1016/j.gene.2014.05.060 |
| Popis: | Left ventricular dysfunction (LVD) is a complex, multifactorial condition, caused by mechanical, neurohormonal, and genetic factors. We have previously observed association of renin-angiotensin-aldosterone system (RAAS), matrix metalloproteinases (MMPs) and inflammatory pathway genes with LVD. Therefore the present study was undertaken to identify the combination of genetic variants and their possible interactions contributing towards genetic susceptibility to LVD in the background of coronary artery disease (CAD).The study included 230 healthy controls and 510 consecutive patients with angiographically confirmed CAD. Among them, 162 with reduced left ventricle ejection fraction (LVEF≤45%) were categorized as having LVD. We analyzed 11 polymorphisms of RAAS, MMPs and inflammatory pathways. Single locus analysis showed that AT1 A1166C (p value0.001; OR=3.67), MMP9 R668Q (p value=0.007; OR=3.48) and NFKB1-94 ATTG ins/del (p value=0.013; OR=2.01) polymorphisms were independently associated with LVD when compared with both non-LVD patients and healthy controls. High-order gene-gene interaction analysis, using classification and regression tree (CART) and multifactor dimensionality reduction (MDR) revealed that AT1 A1166C and NFKB1-94 ATTG ins/del polymorphisms jointly increased the risk of LVD to great extent (p-value=0.001; OR=8.55) and best four-factor interaction model consisted of AT1 A1166C, MMP7 A-181G, MMP9 R668Q and NFKB1-94 ATTG ins/del polymorphisms with testing accuracy of 0.566 and cross validation consistency (CVC)=9/10 (permutation p0.001) showed increased risk for LVD respectively.AT1 A1166C independently and in combination with MMP9 R668Q and NFKB1-94 ATTG ins/del polymorphisms plays important role in conferring genetic susceptibility to LVD in CAD patients. |
| Databáze: | OpenAIRE |
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