title: H558R polymorphism in SCN5A is associated with Keshan disease and QRS prolongation in Keshan disease patients.
abstract: Keshan disease (KSD), a potentially fatal cardiomyopathy, has very high incidence in some selenium-poor regions of China. KSD may be accompanied with a variety of arrhythmia, which is associated with mutations in the gene coding for cardiac voltage-gated sodium channel (SCN5A). The molecular mechanism of KSD is still largely obscure. We aimed to determine the association between the H558R polymorphism of SCN5A and KSD. We recruited 71 patients with KSD and 80 geographical region-matched control subjects in our study. Vital sign and electrocardiographic (ECG) measurements were performed for heart rate, systolic pressure, diastolic pressure, PR interval, QT interval, QRS duration, ST-T changes and complete right bundle branch block (CRBBB), and H558R polymorphism was genotyped using the polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) method and sequencing. A significant association was found between the H558R polymorphism of exon 12 and KSD. Allele C carriers had a decreased risk for KSD with an odds ratio of 0.332 [95% confidence interval (CI), 0.160-0.692] as well as for QRS prolongation in KSD patients with an odds ratio of 0.089 (95%CI, 0.022-0.361). Our results provide support to the association between H558R polymorphism and the decreased risk for KSD. H558R polymorphism might increase susceptibility to KSD, and SCN5A containing the polymorphism might be a predisposing gene for QRS prolongation.
authors.affiliation: Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: S
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.
authors.forename: F L
authors.initials: FL
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Dong
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.
authors.forename: H W
authors.initials: HW
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.
authors.forename: C F
authors.initials: CF
authors.lastname: Fang
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.
authors.forename: C
authors.initials: C
authors.lastname: Shu
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.
authors.forename: H
authors.initials: H
authors.lastname: Cheng
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China.
authors.forename: J
authors.initials: J
authors.lastname: Cui
authors.affiliation: Daqing First Hospital, Da Qing, China.
authors.forename: H X
authors.initials: HX
authors.lastname: Ma
authors.affiliation: Qiqihar First Hospital, Qiqihar, China.
authors.forename: D Q
authors.initials: DQ
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China lihui@ems.hrbhmu.edu.cn.
authors.forename: H
authors.initials: H
authors.lastname: Li
mesh_terms: D000368:Aged; D001794:Blood Pressure; D009202:Cardiomyopathies / Q000235:genetics* / Q000503:physiopathology; D002681:China; D015331:Cohort Studies; D004252:DNA Mutational Analysis / Q000379:methods; D004562:Electrocardiography; D004769:Enterovirus Infections / Q000235:genetics* / Q000503:physiopathology; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006339:Heart Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics*; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D012307:Risk Factors
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human