Genetic polymorphisms in KCNQ1, HERG, KCNE1 and KCNE2 genes in the Chinese, Malay and Indian populations of Singapore.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Koo
Seok Hwee
SH
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Ho
Woon Fei
WF
Lee
Edmund Jon Deoon
EJ
D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; D002681:China / Q000208:ethnology; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics; D006801:Humans; D007194:India / Q000208:ethnology; D047668:Inteins / Q000235:genetics; D051657:KCNQ1 Potassium Channel / Q000235:genetics; D008133:Long QT Syndrome / Q000235:genetics; D008296:Malaysia / Q000208:ethnology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics*; D012846:Singapore / Q000453:epidemiology
D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C489622:KCNE1 protein, human; C489619:KCNE2 protein, human; C000606913:KCNH2 protein, human; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D024642:Potassium Channels, Voltage-Gated