KvLQT1 and KCNE1 K+ Channel Gene Polymorphisms in Long QT Syndrome
Sameera F. Qureshi
Department of Genetics, University College of Science, Osmania University, Hyderabad-500007, Andhra Pradesh, India.
Altaf Ali
Department of Genetics, University College of Science, Osmania University, Hyderabad-500007, Andhra Pradesh, India.
Ananthapur Venkateshwari
nstitute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet, Hyderabad-500016, Andhra Pradesh, India.
M. P. Jayakrishnan
Institute of Maternal and Child Health, Calicut Medical College, Calicut 8, Kerala, India.
Calambur Narasimhan
Care Hospital, Hyderabad, Andhra Pradesh, India.
Jayaprakash Shenthar
Sri Jayadeva Institute of Cardiovascular Science and Research, Jayanagar 9th Block, Bannerghatta Road, Bangalore 560069, Karnataka, India
Kumarasamy Thangaraj
Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, Andhra Pradesh, India.
Pratibha Nallari *
Department of Genetics, University College of Science, Osmania University, Hyderabad-500007, Andhra Pradesh, India.
*Author to whom correspondence should be addressed.
Abstract
Long QT Syndrome (LQTS), a disorder of the cardiac repolarization process with prolongation of the QT interval (QTc ≥0.46 seconds), is an ion-channelopathy. Mutations in either KCNQ1 or KCNE1 genes are susceptible to LQTS. Hence, screening of KCNQ1 and KCNE1 genes is taken up to evaluate the genetic correlation of these genes in Long QT patients of Indian origin.
A total of 33 Long QT Syndrome patients and 100 healthy subjects were enrolled for the present study. PCR-SSCP protocol was utilised for screening of KCNQ1 and KCNE1 genes followed by In-silico and statistical analysis.
The clinical profile of the Long QT syndrome patients in our study revealed a higher percentage of females with the mean age also being higher in females when compared to males. The two variations (S546S and IVS13+36A>G) in KCNQ1 and the S38G polymorphism in KCNE1 gene were identified and their association with Long QT syndrome is being reported for the first time in Indian population. S546S is located in the KCNQ1 C terminus close to this domain and IVS13+36A>G is located in the intronic region in close proximity to the coding region for C-terminal domain; these may therefore affect the functional protein through non-assembly. S38G leads to a substitution of serine to glycine at 38th amino acid position (S38G) in the transmembrane domain of KCNE1.
Our study reports compound heterozygosity/genetic compound ofS546S and IVS13+36A>G of KCNQ1 gene. Haplotype frequencies and linkage disequilibrium analysis revealed a significant association between the three biomarkers. Compound heterozygosity of the polymorphisms influence downstream signalling and KCNQ1-KCNE1 interactions.
Keywords: Long QT syndrome, compound heterozygotes, KCNQ1, KCNE1, linkage disequilibrium, C-terminal domain