title: Genetic variability of RyR2 and CASQ2 genes in an Asian population.
abstract: We analyzed the coding regions of the cardiac calcium-handling genes, ryanodine receptor 2 (RyR2) and calsequestrin 2 (CASQ2) for genetic variants in a healthy Chinese population (n=95) and in a cohort of 28 sudden unexplained death victims. Mutations in RyR2 and CASQ2 have been shown to alter calcium homeostasis during excitation-contraction coupling and predispose individuals to fatal cardiac arrhythmias. The genetic screening was accomplished by denaturing high-performance liquid chromatography and DNA sequencing methods. Genetic analysis revealed the following non-synonymous genetic variations: two reported RyR2 polymorphisms; 5654G>A (G1885E) and 5656G>A (G1886S), two reported CASQ2 polymorphisms; 196A>G (T66A) and 226G>A (V76M) and one novel CASQ2 mutation; 529G>C (E177Q). The functional significance of the novel CASQ2 mutation has not been evaluated and characterized. This study shows that multiple genetic variations of the RyR2 and CASQ2 genes exist in the two study populations. The inter-individual genetic variability may underlie the different susceptibility of individuals to developing ventricular tachycardia. The research results will be valuable for which future work involving clinical and forensic samples can be based upon to distinguish potential disease-associated mutations from common polymorphisms.
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Drive, Singapore.
authors.forename: Chang Hua
authors.initials: CH
authors.lastname: Wong
authors.forename: Seok Hwee
authors.initials: SH
authors.lastname: Koo
authors.forename: George Qiongze
authors.initials: GQ
authors.lastname: She
authors.forename: Paul
authors.initials: P
authors.lastname: Chui
authors.forename: Edmund Jon Deoon
authors.initials: EJ
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics*; D002155:Calsequestrin / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid; D015331:Cohort Studies; D003645:Death, Sudden; D005260:Female; D053803:Forensic Genetics; D005828:Genetics, Population; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*; D017422:Sequence Analysis, DNA; D012846:Singapore; D055815:Young Adult
chemical_list: C443109:CASQ2 protein, human; D002155:Calsequestrin; D019837:Ryanodine Receptor Calcium Release Channel