From the Department of Cardiology, Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB), Universidad de Murcia, Murcia, Department of Cardiology, Hospital General Universitario, Alicante, Department of Cardiology, Hospital General Universitario de Elche, Alicante, Departament of Molecular Biology, Centro Inmunológico de Alicante, Alicante, Department of Radioimmunoanalysis, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain and Centre for Cardiovascular Sciences, City Hospital, University of Birmingham, Birmingham, UK.
From the Department of Cardiology, Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca (IMIB), Universidad de Murcia, Murcia, Department of Cardiology, Hospital General Universitario, Alicante, Department of Cardiology, Hospital General Universitario de Elche, Alicante, Departament of Molecular Biology, Centro Inmunológico de Alicante, Alicante, Department of Radioimmunoanalysis, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain and Centre for Cardiovascular Sciences, City Hospital, University of Birmingham, Birmingham, UK
QJM. 2014 Aug;107(8):613-21. doi: 10.1093/qjmed/hcu046. Epub 2014 Mar 5.
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.
一些非肌节基因被认为是肥厚型心肌病（HCM）表型表现的修饰因子。HCM 中房颤（AF）的发展具有不良预后意义，会增加血栓栓塞和功能障碍的风险。
我们检验了以下假设，即 2 个非肌节基因 [CYP11B2（-344T>C）和 COL1A1（2046G>T）] 与 AF 的发生有关。
前瞻性研究。
在 159 例 HCM 患者（49.3±14.9 岁，70.6%为男性）和 136 例对照者中分析了非肌节基因 [CYP11B2（-344T>C）和 COL1A1（2046G>T）] 中的 2 个多态性。所有受试者在研究入组时临床稳定且处于窦性心律，没有缺血性心脏病或其他可能掩盖分析多态性影响的重要合并症（即既往 AF）。在中位随访 49.5 个月期间，39 例患者（24.4%）发生 AF。
CYP11B2 基因中的-344T>C 多态性患者发生 AF 的风险更高[HR：3.31（95%CI 1.29-8.50）；P=0.008]。在多变量分析中，CYP11B2 基因中的 C 等位基因的存在[HR：3.02（1.01-8.99）；P=0.047]、既往 AF[HR：2.81（1.09-7.23）；P=0.033]和左心房直径≥42mm[HR：2.69（1.01-7.18）；P=0.048]是 AF 发生的独立预测因子。多态性等位基因的存在与较高的醛固酮血清水平相关。
我们首次表明，CYP11B2 多态性是 HCM 患者 AF 发生的独立预测因子。这突出了非肌节基因在 HCM 表型异质性中的重要性。与较高的醛固酮血清水平相关可能与更大的纤维化和心脏重塑有关。
