Association of MMP-9 gene polymorphisms with atrial fibrillation in hypertensive heart disease patients

Abstract

Background: MMP-9 plays an important role in the pathogenesis of arrhythmogenic atrial remodeling, and may contribute to the development and persistence of atrial fibrillation (AF). Functional polymorphisms in the MMP-9 gene which lead to altered MMP-9 production and/or activity may modulate an individual's susceptibility to AF.

Methods: A total of 881 hypertensive heart disease patients of Chinese Han population (128 with and 753 without AF) were recruited in this study. The MMP-9 -1562C>T and R279Q genotypes were determined using PCR-RFLP method. The plasma concentration of MMP-9 was measured by ELISA.

Results: Both the genotype distributions and allele frequencies of the -1562C>T polymorphism were significantly different between the AF and control group (P=0.007 and P=0.002, respectively). The T allele carriers (TT + CT) had significantly increased risk of AF compared with the CC homozygotes (OR 1.94, 95% CI 1.20-3.14; adjusted P=0.006) in a logistic regression model after controlling age, left atrial dimension, and the use of angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers. The T allele carriers also had increased plasma MMP-9 levels compared with CC homozygotes in both AF patients and control subjects. No relationship between R279Q polymorphism and AF was found in this cohort.

Conclusions: The -1562C>T polymorphism of MMP-9 gene is significantly associated with AF risk in Chinese Han patients with hypertensive heart disease. The -1562T allele which is associated with increased expression of MMP-9 might be a genetic risk for the development of AF in this cohort.