Genetic variability of RyR2 and CASQ2 genes in an Asian population

Wong, Chang Hua; Koo, Seok Hwee; She, George Qiongze; Chui, Paul; Lee, Edmund Jon Deoon

doi:10.1016/j.forsciint.2009.07.019

« Previous Next »Forensic Science International
Volume 192, Issue 1 , Pages 53-55, 20 November 2009

Genetic variability of RyR2 and CASQ2 genes in an Asian population

Chang Hua Wong
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Block MD11, Clinical Research Centre, Level 5, #05-09, 10 Medical Drive, Singapore 117597, Singapore
Seok Hwee Koo
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Block MD11, Clinical Research Centre, Level 5, #05-09, 10 Medical Drive, Singapore 117597, Singapore
George Qiongze She
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Block MD11, Clinical Research Centre, Level 5, #05-09, 10 Medical Drive, Singapore 117597, Singapore
Paul Chui
- Forensic Medicine Division, Health Sciences Authority, 11 Outram Road, Singapore 169078, Singapore
Edmund Jon Deoon Lee
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Block MD11, Clinical Research Centre, Level 5, #05-09, 10 Medical Drive, Singapore 117597, Singapore
- Corresponding author. Tel.: +65 65163677; fax: +65 68737690.

Received 19 June 2008; received in revised form 20 March 2009; accepted 28 July 2009. published online 26 August 2009.

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.