Matrix metalloproteinase 1 promoter polymorphisms and risk of myocardial infarction: a case-control study in a Spanish population.
OBJECTIVE
Inherited and acquired risk factors contribute to the development of the atherosclerotic lesion and its most common clinical manifestation, myocardial infarction (MI). Multiple studies have suggested a role for matrix metalloproteinases (MMPs) in atherosclerosis, and several functional polymorphisms in the MMP-1 gene have been linked to the risk of MI. The aim of this study was to evaluate the association between MMP-1 promoter polymorphisms and early MI in a Spanish cohort.


METHODS
We carried out a case-control study with 261 unrelated patients who had suffered an MI before 55 years of age and 194 healthy controls, all male and smokers. The genotypes for the three MMP-1 promoter polymorphisms -1607 1G/2G, -519 A/G, and -340 T/C were determined through PCR-restriction fragment length polymorphism. Allelic, genotypic, and haplotypic frequencies were statistically compared between groups.


RESULTS
Frequencies of the three polymorphisms did not differ between patients and controls. The -1607 1G/2G and -519 A/G variants were in linkage disequilibrium. Analysis of the haplotype frequencies showed significant associations of the 2G(-1607)-G(-519)-T(-340) (odds ratio = 2.40; 95% confidence interval = 1.27-4.55; P<0.006) and 1G(-1607)-G(-519)-T(-340) (odds ratio = 0.68; 95% confidence interval = 0.50-0.94; P<0.05) haplotypes with the risk of early MI.


CONCLUSIONS
MMP-1 promoter polymorphisms are associated with the risk of early MI in a Spanish population of smoking males.
Román-García
Pablo
P
Servicio de Metabolismo Oseo y Mineral, Hospital Universitario Central de Asturias, Oviedo, Spain.
Coto
Eliecer
E
Reguero
Julián R
JR
Cannata-Andía
Jorge B
JB
Lozano
Iñigo
I
Avanzas
Pablo
P
Morís
César
C
Rodríguez
Isabel
I
D000328:Adult; D016022:Case-Control Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000201:enzymology / Q000235:genetics*; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D018570:Risk Assessment; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects; D013030:Spain
C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1