Koo Seok Hwee, Ho Woon Fei, Lee Edmund Jon Deoon
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Br J Clin Pharmacol. 2006 Mar;61(3):301-8. doi: 10.1111/j.1365-2125.2005.02545.x.
To determine the genetic variability of long QT syndrome (LQTS)-associated genes (KCNQ1, HERG, KCNE1 and KCNE2) among three distinct ethnic groups in the Singapore population.
Genomic DNA samples from up to 265 normal healthy Chinese, 118 Malay and 139 Indian volunteer subjects were screened for genetic variations in the coding region of the LQTS-associated genes using denaturing high-performance liquid chromatography and sequencing analyses.
In total, 37 single nucleotide polymorphisms (SNPs) were identified in the coding exons of the LQTS-associated potassium ion channel genes, seven of which were novel nonsynonymous polymorphisms. SNPs 356G-->A (exon 1 of KCNQ1), 2624C-->T and 2893G-->A (exon 11 of HERG), 3164G-->A, 3322C-->G and 3460G-->A (exon 14 of HERG), and 79C-->T (exon 3 of KCNE2) resulted in Gly119Asp, Thr875Met, Gly965Arg, Arg1055Gln, Leu1108Val, Gly1154Ser and Arg27Cys amino acid substitutions, respectively. In addition, 16 intronic variants were detected. The functional consequence of these variants has not been studied and their association with risk of LQTS is unclear.
There exist multiple genetic polymorphisms of the LQTS-associated genes in the three distinct Asian populations. Though the functional significance of many of these SNPs is unknown, this interindividual and interethnic genetic variability may underlie the different susceptibilities of individuals to developing LQTS.
确定新加坡人群中三个不同种族群体的长QT综合征（LQTS）相关基因（KCNQ1、HERG、KCNE1和KCNE2）的遗传变异性。
使用变性高效液相色谱和测序分析，对多达265名正常健康的中国志愿者、118名马来志愿者和139名印度志愿者的基因组DNA样本进行LQTS相关基因编码区的遗传变异筛查。
总共在LQTS相关钾离子通道基因的编码外显子中鉴定出37个单核苷酸多态性（SNP），其中7个是新的非同义多态性。SNP 356G→A（KCNQ1外显子1）、2624C→T和2893G→A（HERG外显子11）、3164G→A、3322C→G和3460G→A（HERG外显子14）以及79C→T（KCNE2外显子3）分别导致Gly119Asp、Thr875Met、Gly965Arg、Arg1055Gln、Leu1108Val、Gly1154Ser和Arg27Cys氨基酸替换。此外，检测到16个内含子变异。这些变异的功能后果尚未研究，它们与LQTS风险的关联尚不清楚。
在三个不同的亚洲人群中存在LQTS相关基因的多种遗传多态性。尽管许多这些SNP的功能意义尚不清楚，但这种个体间和种族间的遗传变异性可能是个体对发生LQTS易感性不同的基础。
