MMP13 promoter polymorphism is associated with atherosclerosis in the abdominal aorta of young black males.
Previous studies suggested that remodeling of connective tissue is important in progression of atherosclerosis. We investigated the importance of matrix metalloproteinase 13 (MMP13), in the pathogenesis of atherosclerosis using 995 samples from the Pathobiological Determinants of Atherosclerosis in Youth collection in an association study. We identified two new MMP13 promoter polymorphisms. The genotype for one of the MMP13 polymorphisms was associated with fibrous plaque (P=0.024) in black males. Immunohistochemistry using antibodies for MMP13 showed that MMP13 is expressed in all layers of the aorta. In-vitro transfection experiments with reporter gene constructs and electrophoretic mobility-shift assays showed that the MMP13 polymorphism was a functional variant. MMP13 is therefore, a genetic risk factor for extent of fibrous plaque in the abdominal aorta in young black males. Elucidation of the currently unknown mechanism of the MMP13 polymorphism's action may provide for pharmacological intervention to reduce the severity of atherosclerotic changes in susceptible individuals.
Yoon
Sungpil
S
The Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detriot, MI 48201, USA.
Kuivaniemi
Helena
H
Gatalica
Zoran
Z
Olson
Jane M
JM
Butticè
Giovanna
G
Ye
Siqin
S
Norris
Brent A
BA
Malcom
Gray T
GT
Strong
Jack P
JP
Tromp
Gerard
G
D000293:Adolescent; D000328:Adult; D001012:Aorta, Abdominal / Q000378:metabolism; D001161:Arteriosclerosis / Q000235:genetics* / Q000378:metabolism; D044383:Black People / Q000235:genetics*; D017364:Collagenases / Q000235:genetics* / Q000378:metabolism; D005787:Gene Frequency; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D053509:Matrix Metalloproteinase 13; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014407:Tumor Cells, Cultured
D017364:Collagenases; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13