Prognostic value of two polymorphisms in non-sarcomeric genes for the development of atrial fibrillation in patients with hypertrophic cardiomyopathy

Several non-sarcomeric genes have been postulated to act as modifiers in the phenotypic manifestations of hypertrophic cardiomyopathy (HCM). The development of atrial fibrillation (AF) in HCM has adverse prognostic implications with increased thromboembolism and functional class impairment. We teste...

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Bibliographic Details
Published in:QJM : An International Journal of Medicine 2014-08, Vol.107 (8), p.613-621
Main Authors: Orenes-Piñero, E, Hernández-Romero, D, Romero-Aniorte, A I, Martínez, M, García-Honrubia, A, Caballero, L, Garrigos-Gómez, N, Andreu-Cayuelas, J M, González, J, Feliu, E, Climent, V, Nicolás-Ruiz, F, De La Morena, G, Valdés, M, Lip, G Y H, Marín, F
Format: Article
Language:English
Subjects:
Adult
Aged
Aldosterone - blood
Atrial Fibrillation - blood
Atrial Fibrillation - etiology
Atrial Fibrillation - genetics
Cardiomyopathy, Hypertrophic - blood
Cardiomyopathy, Hypertrophic - complications
Cardiomyopathy, Hypertrophic - genetics
Case-Control Studies
Collagen Type I - genetics
Cytochrome P-450 CYP11B2 - genetics
Female
Gene Frequency
Genetic Predisposition to Disease
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Polymorphism, Single Nucleotide
Prognosis
Prospective Studies
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Summary:Several non-sarcomeric genes have been postulated to act as modifiers in the phenotypic manifestations of hypertrophic cardiomyopathy (HCM). The development of atrial fibrillation (AF) in HCM has adverse prognostic implications with increased thromboembolism and functional class impairment. We tested the hypothesis that 2 non-sarcomeric genes [CYP11B2 (-344T>C) and COL1A1 (2046G>T)] are associated with the development of AF. Prospective study. Two polymorphisms in non-sarcomeric genes [CYP11B2 (-344T>C) and COL1A1 (2046G>T)] were analysed in 159 HCM patients (49.3 ± 14.9 years, 70.6% male) and 136 controls. All subjects were clinically stable and in sinus rhythm at entry in the study, without ischemic heart disease or other significant co-morbidities that could mask the effect of the analysed polymorphisms (i.e. previous AF). Thirty-nine patients (24.4%) developed AF during a median follow-up of 49.5 months. Patients with the -344T>C polymorphism in CYP11B2 gene had a higher risk for AF development [HR: 3.31 (95% CI 1.29-8.50); P = 0.008]. In a multivariate analysis, the presence of the C allele in CYP11B2 gene [HR: 3.02 (1.01-8.99); P = 0.047], previous AF [HR: 2.81 (1.09-7.23); P = 0.033] and a left atrial diameter of ≥42 mm [HR: 2.69 (1.01-7.18); P = 0.048] were independent predictors of AF development. The presence of the polymorphic allele was associated with higher aldosterone serum levels. We have shown for the first time that the CYP11B2 polymorphism is an independent predictor for AF development in HCM patients. This highlights the importance of non-sarcomeric genes in the phenotypic heterogeneity of HCM. The association with higher aldosterone serum levels could relate to greater fibrosis and cardiac remodelling.
ISSN:1460-2725
1460-2393
DOI:10.1093/qjmed/hcu046