Association of matrix metalloproteinases (MMP2, MMP7 and MMP9) genetic variants with left ventricular dysfunction in coronary artery disease patients.
BACKGROUND
Left ventricular dysfunction (LVD) is a condition resulting from clustered structural or functional cardiac disorder that reduces the ability of the ventricle to fill with or eject blood. The impaired ventricular function can be attributed to unfavorable ventricular remodeling. Among the pathways that contribute to remodeling process, matrix metalloproteinases (MMPs) appear to be of particular interest. We explored the association of MMP2 (C-735T, rs2285053), MMP7 (A-181G, rs11568818) and MMP9 (R279Q, rs17576), (P574R, rs2250889), (R668Q, rs17577) genetic variants with LVD in coronary artery disease (CAD) patients.


METHODS
The study included 310 consecutive patients with angiographically confirmed CAD and 230 healthy controls. Among patients with CAD, 95 with reduced left ventricle ejection fraction (LVEF ≤ 45) were categorized as LVD. Polymorphisms were determined by PCR-RFLP.


RESULTS
The MMP9 R668Q genetic variant was significantly associated with LVD (LVEF ≤ 45) (p value=0.009; OR=3.82). To validate our results, we performed a replication study in additional 200 cases with similar clinical characteristics and results again confirmed consistent findings (p value=0.033; OR=3.59). Also the frequency of haplotype R,P,Q comprising R668Q variation in MMP 9 was significantly higher in reduced LVEF subjects (p value=0.008; OR=1.83).


CONCLUSIONS
MMP9 R668Q plays important role in conferring susceptibility of LVD.
Department of Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences-SGPGIMS, Lucknow-226014 UP, India.
Avshesh
A
Mishra
Anshika
A
Srivastava
T
T
Mittal
N
N
Garg
B
B
Mittal
D000368:Aged; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000150:complications / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006352:Heart Ventricles / Q000201:enzymology / Q000503:physiopathology; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics* / Q000378:metabolism; D020783:Matrix Metalloproteinase 7 / Q000235:genetics* / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D008958:Models, Molecular; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D018487:Ventricular Dysfunction, Left / Q000150:complications / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology
C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9