MMP2 genetic variation is associated with measures of fibrous cap thickness: The Atherosclerosis Risk in Communities Carotid MRI Study.
OBJECTIVE
Genetic variation in matrix metalloproteinase (MMP) promoter regions alter the transcriptional activity of MMPs and has been consistently associated with CHD, presumably through plaque degradation and remodeling. We examined the association of MMP promoter variation with multiple plaque characteristics measured by gadolinium-enhanced MRI among 1700 participants in the Atherosclerosis Risk in Communities (ARIC) Carotid MRI Study.


METHODS
For the analyses presented here, 1700 participants of the biracial ARIC Carotid MRI Study ( approximately 1000 participants with thick carotid artery walls and approximately 700 randomly sampled participants) were evaluated for associations of MMP genetic variation with multiple plaque characteristics, including carotid artery wall thickness, lipid core and fibrous cap measures. MRI studies were performed on a 1.5T scanner equipped with a bilateral 4-element phased array carotid coil.


RESULTS
Fifty-one percent of the participants were female, 77% white, 23% African American, and the mean age was 70 years. MMP2 C-1306T variant genotypes (CT+TT) were significantly associated with higher cap thickness measures, but not with wall thickness or lipid core measures. Individuals with the CC genotype had approximately 0.1mm thinner cap thickness compared to those carrying a T allele (P=0.02).


CONCLUSIONS
Genetic variation within the MMP2 promoter region was associated with cap thickness and therefore may influence the role of MMP2 in plaque vulnerability.
Volcik
Kelly A
KA
University of Texas Health Science Center School of Public Health, Human Genetics Center, 1200 Hermann Pressler, Houston, TX 77030, United States. Kelly.A.Volcik@uth.tmc.edu
Campbell
Stephen
S
Chambless
Lloyd E
LE
Coresh
Josef
J
Folsom
Aaron R
AR
Mosley
Thomas H
TH
Ni
Hanyu
H
Wagenknecht
Lynne E
LE
Wasserman
Bruce A
BA
Boerwinkle
Eric
E
D000368:Aged; D050197:Atherosclerosis / Q000235:genetics* / Q000473:pathology*; D002339:Carotid Arteries / Q000473:pathology*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011446:Prospective Studies; D014158:Transcription, Genetic
D020778:Matrix Metalloproteinase 2