Association of Atrial Myocardial Fibrosis with a Common Matrix Metalloproteinase-2 Promoter Polymorphism

• Published in: Heart rhythm Vol. 9; no. 11; p. 1921
• Main Authors: Ji, S, Yarmohammadi, H, Hoyt, H, Hansford, R, Zviman, M.M, Steinberg, S.J, Judge, D.P, Caffo, B.S, Tomaselli, G.F, Halperin, H.R, Cheng, A, Spragg, D.D, Henrikson, C.A, Sinha, S, Marine, J.E, Berger, R, Calkins, H, Nazarian, S
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01-11-2012
• Subjects: Cardiovascular
• ISSN: 1547-5271; 1556-3871
• DOI: 10.1016/j.hrthm.2012.09.123

Background Atrial fibrillation (AF), the most common cardiac arrhythmia, is associated with the common –1306C/T matrix metalloproteinase-2 single nucleotide polymorphism (MMP2 SNP), which reduces the synthesis of matrix metalloproteinase-2 enzyme. Understanding the factors that mediate this association may improve current preventive and therapeutic strategies for AF. Methods To test the hypothesis that MMP2 SNP is associated with atrial fibrosis, the study was designed as a single center, observational, cross-sectional study. One hundred consecutive patients with symptomatic drug-resistant AF who underwent catheter ablation between September 2009 and February 2011 were enrolled. The endocardial bipolar electrogram voltage was measured point by point in the left atrium as panel data clustered by patient and compared with the result of genetic testing for MMP2 SNP. Results MMP2 SNP was present in at least 1 copy in 43% of patients, the minor allele frequency was 0.27, and genotype frequencies were in Hardy-Weinberg equilibrium (Χ2 = 2.34, P = .126). The overall mean atrial voltage for the 4878 measures in 87 patients was 0.89 ± 1.10 mV. MMP2 SNP was significantly associated with reduced bipolar voltage in codominant (–0.11 mV per T copy, P = .003) and dominant (–0.18 mV if CT or TT, P <.001) models clustered by patient and adjusted for age, ethnicity, gender, body mass index, coronary artery disease, hypertension, paroxysmal vs persistent AF, left atrial size, left ventricular ejection fraction, rhythm during voltage sampling, and previous ablations. The results were robust to exclusion of patients with nonsinus rhythm during voltage mapping (n = 13) and of those with prior ablation procedures (n = 5). Conclusions We report a strong association between a common MMP2 promoter polymorphism and atrial scar fibrosis. Impaired tissue remodeling may mediate the previously reported association between the –1306C/T MMP2 polymorphism and AF.