MMP-2 and TIMP-2 gene polymorphisms and susceptibility to atrial fibrillation in Chinese Han patients with hypertensive heart disease

Abstract

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. 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. 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. 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.