MMP2 genetic variation is associated with measures of fibrous cap thickness: The Atherosclerosis Risk in Communities Carotid MRI Study.

TitleMMP2 genetic variation is associated with measures of fibrous cap thickness: The Atherosclerosis Risk in Communities Carotid MRI Study.
Publication TypeJournal Article
Year of Publication2010
AuthorsVolcik, KA, Campbell, S, Chambless, LE, Coresh, J, Folsom, AR, Mosley, TH, Ni, H, Wagenknecht, LE, Wasserman, BA, Boerwinkle, E
JournalAtherosclerosis
Volume210
Issue1
Pagination188-93
Date Published2010 May
ISSN1879-1484
KeywordsAged, Atherosclerosis, Carotid Arteries, Female, Genetic Variation, Genotype, Humans, Magnetic Resonance Imaging, Male, Matrix Metalloproteinase 2, Middle Aged, Promoter Regions, Genetic, Prospective Studies, Transcription, Genetic
Abstract

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).CONCLUSION: Genetic variation within the MMP2 promoter region was associated with cap thickness and therefore may influence the role of MMP2 in plaque vulnerability.

DOI10.1016/j.atherosclerosis.2009.12.006
Alternate JournalAtherosclerosis
PubMed ID20064641
PubMed Central IDPMC2862087
Grant ListN01HC55020 / HL / NHLBI NIH HHS / United States
N01HC55018 / HL / NHLBI NIH HHS / United States
N01-HC-55022 / HC / NHLBI NIH HHS / United States
U01 HL075572-04 / HL / NHLBI NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
U01 HL075572 / HL / NHLBI NIH HHS / United States
N01HC55022 / HL / NHLBI NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
N01HC55015 / HL / NHLBI NIH HHS / United States
N01-HC-55019 / HC / NHLBI NIH HHS / United States
N01-HC-55015 / HC / NHLBI NIH HHS / United States
N01-HC-55020 / HC / NHLBI NIH HHS / United States
N01HC55016 / HL / NHLBI NIH HHS / United States
N01HC55019 / HL / NHLBI NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States
N01HC55021 / HL / NHLBI NIH HHS / United States