Key result
SCN5A gene polymorphisms, including novel compound heterozygotes, were significantly associated with prolonged QTc in a South Indian cohort with long QT syndrome.
Observational
Specific SCN5A polymorphisms and compound heterozygotes identified in a South Indian cohort are significantly associated with prolonged QTc and long QT syndrome etiology.
SCN5A variants may refine LQTS risk assessment in South Indians; leaves open generalizability and prospective validation.
The SCN5A gene encodes for the INa channel implicated in long QT syndrome type-3 (LQTS-type-3). Clinical symptoms of this type are lethal as most patients had a sudden death during sleep. Screening of SCN5A in South Indian cohort by PCR-SSCP analyses revealed five polymorphisms - A29A (exon-2), H558R (exon-12), E1061E and S1074R (exon-17) and IVS25 + 65G > A (exon-25) respectively. In-silico and statistical analyses were performed on all the polymorphisms. Exon-2 of SCN5A gene revealed A282G polymorphism (rs6599230), resulting in alanine for alanine (A29A) silent substitution in the N-terminus of SCN5A protein. Exon-12 showed A1868G polymorphism (H558R - rs1805124) and its 'AA' genotype and 'A' allele frequency were found to be higher in LQTS patients pointing towards its role in LQTS etiology. Two polymorphisms A3378G (E1061E) and the novel C3417A (S1074R) were identified as compound heterozygotes/genetic compounds in exon-17 of SCN5A located in the DIIS6-DIIIS1 domain of the SCN5A transmembrane protein. IVS25 + 65G > A was identified in intron-25 of SCN5A. The 'G' allele was identified as the risk allele. Variations were identified in in-silico analyses which revealed that these genetic compounds may lead to downstream signaling variations causing aberrations in sodium channel functions leading to prolonged QTc. The compound heterozygotes of SCN5A gene polymorphisms revealed a significant association which may be deleterious/lethal leading to an aberrant sodium ion channel causing prolonged QTc.
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Qureshi et al. (2015) conducted an observational in Long QT syndrome. SCN5A gene polymorphisms was evaluated on Prolonged QTc. SCN5A gene polymorphisms, including novel compound heterozygotes, were significantly associated with prolonged QTc in a South Indian cohort with long QT syndrome.
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