MMP 1 circulating levels and promoter polymorphism in risk prediction of coronary artery disease in asymptomatic first degree relatives.
Coronary artery disease (CAD) remains to be the prominent health problem in India, and its incidence is growing in developing countries as well. Matrix metalloproteinase 1 (MMP 1) is highly expressed in disruption-prone shoulder regions of the fibrous plaques. The present study aims to investigate association of MMP 1 gene polymorphisms (-1607 1G/2G) and serum circulating levels with CAD. The study includes 300 CAD patients, 100 FDRS, and 300 controls. ELISA and PCR-RFLP were performed to determine MMP 1 serum levels and genotypes respectively. MMP1 levels were high in CAD patients, followed by FDRS compared to controls (2.15±1.2ng/ml; 1.46±1.04ng/ml and 0.96±0.53ng/ml) respectively. ROC analysis showed the AUC at 95% CI of serum MMP-1 to be 0.83 and 0.73-0.94, respectively. The optimal cut-off point (sensitivity; specificity) of serum MMP 1 was >1.5ng/ml (0.74; 0.90). The 2G/2G genotype was associated with high MMP 1 circulating levels in CAD patients, and a similar trend was observed in FDRS and controls. The pre-mRNA secondary structure of the 2G allele is much more stable than 1G allele. Our results suggest MMP 1 serum levels and polymorphism as potential independent prognostic markers for future cardiovascular events. These may also help to stratify CAD patients and to identify susceptibility for CAD in asymptomatic healthy FDRS.
Department of Genetics, Osmania University, Hyderabad 500 007, Telangana State, India.
Mrudula Spurthi
MS
Kondapalli
Department of Genetics, Osmania University, Hyderabad 500 007, Telangana State, India.
Rajesh Kumar
RK
Galimudi
Department of Genetics, Osmania University, Hyderabad 500 007, Telangana State, India.
Kishore Kumar
KK
Gundapaneni
Department of Genetics, Osmania University, Hyderabad 500 007, Telangana State, India.
Chiranjeevi
C
Padala
Department of Genetics, Osmania University, Hyderabad 500 007, Telangana State, India.
Anuradha
A
Cingeetham
Department of Genetics, Osmania University, Hyderabad 500 007, Telangana State, India.
Srilatha
S
Gantala
Department of Genetics, Osmania University, Hyderabad 500 007, Telangana State, India.
Altaf
A
Ali
Department of Genetics, Osmania University, Hyderabad 500 007, Telangana State, India.
Nivas
N
Shyamala
Durgabai Deshmukh Hospital and Research Center, Vidyanagar, Hyderabad 500 007, Telangana State, India.
Sanjib Kumar
SK
Sahu
Department of Genetics, Osmania University, Hyderabad 500 007, Telangana State, India.
Pratibha
P
Nallari
Department of Genetics, Osmania University, Hyderabad 500 007, Telangana State, India. Electronic address: surekharanih@gmail.com.
Surekha Rani
SR
Hanumanth
D000328:Adult; D000483:Alleles; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000097:blood / Q000235:genetics; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic
C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1
Coronary artery disease (CAD); First-degree relatives (FDRS); Matrix metalloproteinase 1 (MMP 1); Receiver operating characteristic (ROC) curve