Association of a functional polymorphism in the MMP-3 gene with Moyamoya Disease in the Chinese Han population.
BACKGROUND
Moyamoya disease (MMD) is an uncommon cerebrovascular disease characterized by progressive stenosis of the intracranial internal carotid arteries and their proximal branches. The important role of genetic factors in the etiology and pathogenesis of MMD is being increasingly recognized. The study was designed to examine the association of single nucleotide polymorphisms in matrix metalloproteinase (MMP) and tissue inhibitors of metalloproteinase (TIMP) genes with MMD occurrence.


METHODS
A case-control study was performed. Five functional promoter polymorphisms in the MMP-2, MMP-3, MMP-9 and MMP-13 genes and a potentially functional promoter polymorphism in the TIMP-2 gene were determined by polymerase chain reaction-restriction fragment length polymorphism. Their associations with MMD were analyzed by multivariate logistic regression.


RESULTS
In total, 208 definite patients with MMD (including 31 familial MMD, FMMD, patients) and 224 healthy subjects were recruited. The frequency of the MMP-3 5A/6A and 5A/5A genotypes was significantly lower in MMD patients (OR = 0.57, 95% CI 0.38-0.86, p(corr) = 0.042) compared with healthy controls in a dominant genetic model. Significant differences of the MMP-3 5A/6A polymorphism were also detected between FMMD patients and controls both in the dominant genetic model (OR = 0.23, 95% CI 0.08-0.68, p(corr) = 0.048) and the additive genetic model (OR = 0.24, 95% CI 0.08-0.69, p(corr) = 0.048).


CONCLUSIONS
The functional polymorphism in the MMP-3 promoter might be associated with susceptibility to both MMD and FMMD in the Chinese Han population. The findings need to be validated in further studies including more subjects from different populations.
Li
Hao
H
Beijing Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, Beijing, PR China.
Zhang
Zheng-Shan
ZS
Liu
Wei
W
Yang
Wei-Zhong
WZ
Dong
Zhen-Nan
ZN
Ma
Mai-Juan
MJ
Han
Cong
C
Yang
Hong
H
Cao
Wu-Chun
WC
Duan
Lian
L
D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002681:China; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D009072:Moyamoya Disease / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D016017:Odds Ratio; D010641:Phenotype; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D018570:Risk Assessment; D012307:Risk Factors; D055815:Young Adult
C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3