MMP-2 and TIMP-2 gene polymorphisms and susceptibility to atrial fibrillation in Chinese Han patients with hypertensive heart disease.
BACKGROUND
MMP-2 and TIMP-2 play important roles in the pathogenesis of arrhythmogenic atrial remodeling, and may contribute to the development and persistence of atrial fibrillation (AF). Functional polymorphisms in the promoter of MMP-2 and TIMP-2 gene may modulate an individual's susceptibility to AF.


METHODS
A total of 881 hypertensive heart disease patients from Chinese Han population (128 with and 753 without AF) were recruited in this study. The genotypes of the MMP2-1306C>T and -735C>T polymorphisms and TIMP-2 -418G>C polymorphisms were determined using PCR based method. The plasma concentration of TIMP-2 was measured by enzyme-linked immunosorbent assay in a subgroup with 81 patients.


RESULTS
Both genotype distribution and allele frequency of the TIMP-2 -418G>C polymorphism were significantly different between the AF and control group (P=0.005 and P=0.001, respectively). The C allele carriers (GC+CC) had a significantly increased risk of AF compared with the GG homozygotes (odds ratio,1.77, 95% CI 1.21-2.92, P=0.009) in a logistic regression model after adjustment for age, left atrial dimension, left ventricular mass index, and antihypertensive drugs. The C allele carriers also had reduced levels of plasma TIMP-2 levels compared with GG homozygotes in both AF patients and control subjects. No relationship was found in this cohort between the presence of the MMP-2 -1306C>T and -735C>T polymorphism and AF.


CONCLUSIONS
The TIMP-2 -418G>C polymorphism is significantly associated with an increased susceptibility to AF in Chinese Han patients with hypertensive heart disease. The -418C allele, which is associated with a decreased expression of TIMP-2, might be a genetic risk for the development of AF in this cohort.
Gai
Xiaobo
X
Department of Cardiology, Fuzhou General Hospital, Fuzhou, China.
Zhang
Zhigang
Z
Liang
Yonggang
Y
Chen
Zheming
Z
Yang
Xiangyue
X
Hou
Jiake
J
Lan
Xiaopeng
X
Zheng
Weixing
W
Hou
Jianping
J
Huang
Mingfang
M
D000368:Aged; D000369:Aged, 80 and over; D001281:Atrial Fibrillation / Q000097:blood / Q000150:complications / Q000235:genetics*; D002681:China; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006325:Heart Atria / Q000473:pathology; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000150:complications* / Q000235:genetics; D017379:Hypertrophy, Left Ventricular / Q000150:complications / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood / Q000235:genetics*
D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2