The Ser96Ala variant in histidine-rich calcium-binding protein is associated with life-threatening ventricular arrhythmias in idiopathic dilated cardiomyopathy.
The Ser96Ala variant in histidine-rich calcium-binding protein is associated with life-threatening ventricular arrhythmias in idiopathic dilated cardiomyopathy.
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富含组氨酸的钙结合蛋白中的Ser96Ala变体与特发性扩张性心肌病中威胁生命的心室心律失常有关。
DOI：
10.1093/eurheartj/ehn328
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发表时间：
2008-10
影响因子：
39.3
通讯作者：
Kranias, Evangelia G.
中科院分区：
文献类型：
--
作者：
Arvanitis, Demetrios A.;Sanoudou, Despina;Kolokathis, Fotis;Vafiadaki, Elizabeth;Papalouka, Vasiliki;Kontrogianni-Konstantopoulos, Aikaterini;Theodorakis, George N.;Paraskevaidis, Ioannis A.;Adamopoulos, Stamatios;Dorn, Gerald W., II;Kremastinos, Dimitrios Th.;Kranias, Evangelia G.
探讨富组氨酸钙（HRC）结合蛋白的遗传变异是否与特发性扩张型心肌病（DCM）及其进展相关。我们筛选了123例特发性DCM患者和96名健康人的单链构象多态性分析和直接测序的HRC的遗传变异。检测到六种多态性：Leu 35 Leu（A/G）、Ser 43 Asn（G/A）、Ser 96 Ala（T/G）、Glu202_Glu203insGlu（-/GAG）、Asp 261 del（GAT/-），以及在His 321处的51个氨基酸的框内插入。对它们的频率分析没有发现与DCM发展有任何显著相关性。然而，Ser 96 Ala多态性与危及生命的室性心律失常的发生具有统计学显著相关性。在4.02 ± 2.4年的随访期间，Ala/Ala患者发生室性心律失常的风险高于Ser/Ser纯合子患者（HR，9.620; 95% CI，2.183-42.394; P = 0.003）。多因素考克斯回归分析显示，Ser 96 Ala多态性是DCM患者唯一显著的遗传性心律失常发生预测因子（HR，4.191; 95% CI，0.838-20.967; P = 0.018）。HRC的Ser 96 Ala基因变异与特发性DCM中危及生命的室性心律失常相关，并可作为DCM背景下易发生心律失常的独立预测因子。
To investigate whether genetic variants of the histidine-rich calcium (HRC)-binding protein are associated with idiopathic dilated cardiomyopathy (DCM) and its progression. We screened 123 idiopathic DCM patients and 96 healthy individuals by single-strand conformation polymorphism analysis and direct sequencing for genetic variants in HRC. Six polymorphisms were detected: Leu35Leu (A/G), Ser43Asn (G/A), Ser96Ala (T/G), Glu202_Glu203insGlu (−/GAG), Asp261del (GAT/−), and an in-frame insertion of 51 amino acids at His321. The analysis of their frequencies did not reveal any significant correlation with DCM development. However, the Ser96Ala polymorphism exhibited a statistically significant correlation with the occurrence of life-threatening ventricular arrhythmias. During a follow-up of 4.02 ± 2.4 years, the risk for ventricular arrhythmias was higher (HR, 9.620; 95% CI, 2.183–42.394; P = 0.003) in the Ala/Ala patients, compared with Ser/Ser homozygous patients. On multivariable Cox regression analysis, the Ser96Ala polymorphism was the only significant genetic arrythmogenesis predictor in DCM patients (HR, 4.191; 95% CI, 0.838–20.967; P = 0.018). The Ser96Ala genetic variant of HRC is associated with life-threatening ventricular arrhythmias in idiopathic DCM and may serve as an independent predictor of susceptibility to arrhythmogenesis in the setting of DCM.
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DOI：
10.1152/ajpheart.00278.2007
发表时间：
2007-09-01
影响因子：
4.8
作者：
Arvanitis, Demetrios A.;Vafiadaki, Elizabeth;Kranias, Evangelia G.
通讯作者：
Kranias, Evangelia G.
影响因子：
37.8
作者：
Grimm, W;Christ, M;Maisch, B
通讯作者：
Maisch, B
影响因子：
37.8
作者：
Bänsch, D;Antz, M;Kuck, KH
通讯作者：
Kuck, KH
影响因子：
4.4
作者：
HOFMANN, SL;TOPHAM, M;FRANCKE, U
通讯作者：
FRANCKE, U
影响因子：
10.8
作者：
Schmidt, AG;Zhai, J;Kranias, EG
通讯作者：
Kranias, EG