Polymorphisms of MMP-3 and TIMP-4 genes affect angiographic coronary plaque progression in non-diabetic and type 2 diabetic patients.
BACKGROUND
This study examined whether genetic variants of matrix metallopeptidases (MMPs) and their tissue inhibitors (TIMPs) were associated with angiographic coronary plaque progression (PP) in type 2 diabetic and non-diabetic patients.


METHODS
Four hundred and ninety-nine patients were grouped, who underwent coronary angiography and received repeat examinations after 1-y follow-up. Twelve functional polymorphisms of MMPs and TIMPs were characterized.


RESULTS
Genotype distribution and allele frequency of -1612 5A/6A MMP-3 and 3'UTR C/T TIMP-4 differed between patients with PP and those without in both diabetic and non-diabetic groups after Bonferroni's correction (all P<0.0041667, except for allele frequency of MMP-3 [P=0.007] and genotype/allele frequency of TIMP-4 [P=0.04 and P=0.016, respectively] in diabetes). MMP-3 and TIMP-4 polymorphisms were associated with changes in percent diameter stenosis and minimal lumen diameter in diabetic patients, and changes in cumulative coronary obstruction in both diabetic and non-diabetic patients (all P<0.05). Multivariable regression analysis revealed that hypertension, low HDL-C and genotypes of MMP-3 and TIMP-4 were independent determinants of PP in the whole patients, with these 2 genetic factors being associated with PP in diabetic and non-diabetic subgroups.


CONCLUSIONS
This study demonstrated that MMP-3 and TIMP-4 polymorphisms affect angiographic coronary PP in type 2 diabetic and non-diabetic patients.
Chen
Qiu Jing
QJ
Department of Cardiology, Rui Jin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, PR China.
Lu
Lin
L
Peng
Wen Hui
WH
Hu
Jian
J
Yan
Xiao Xiang
XX
Wang
Ling Jie
LJ
Zhang
Qi
Q
Zhang
Rui Yan
RY
Shen
Wei Feng
WF
D000368:Aged; D000483:Alleles; D017023:Coronary Angiography; D054059:Coronary Occlusion / Q000150:complications / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000201:enzymology / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic / Q000235:genetics*; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics* / Q000378:metabolism; D000097792:Tissue Inhibitor of Metalloproteinase-4
D019278:Matrix Metalloproteinase 3; D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4