PubMed 26670457

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: KCNQ1 , Kv7.1

Title: Heat shock protein 70 gene polymorphisms' influence on the electrophysiology of long QT syndrome.

Authors: Altaf Ali, Sameera F Qureshi, Veronica Medikare, Ananthapur Venkateshwari, Narsimhan Calambur, Hygriv Rao, M P Jayakrishnan, Jayaprakash Shenthar, Kumarasamy Thangaraj, Pratibha Nallari

Journal, date & volume: J Interv Card Electrophysiol, 2016 Mar , 45, 119-30

PubMed link:

Long QT syndrome (LQTS) is a rare cardiac disorder caused due to mutations in genes encoding ion channels responsible for generation of electrical impulses. The heat shock protein (HSP)-70 gene, expressed under conditions of stress, plays a cardioprotective role when overexpressed and helps in the proper folding of the nascent proteins synthesized by the cellular machinery. We aimed to identify the role played by HSP-70 gene polymorphisms in the pathogenesis of LQTS.Study included 49 LQTS patients, 71 family members, and 219 healthy individuals recruited from an ethnically matched population. Genotyping of the single-nucleotide polymorphisms (SNPs) rs1043618 (HSP-70-1, +190G/C), rs1061581 (HSP-70-2, +1267A/G), and rs2227956 (HSP-70-hom, +2437T/C) was performed by PCR-RFLP analysis, and the results were analyzed statistically at 95 % confidence interval and p ≤ 0. 05.The "C" allele of HSP-70-1 (+190G/C) and "G" allele of HSP-70-2 (+1267A/G) showed strong association with LQTS phenotype. The haplotype group C-G-T consisting of two risk alleles was significantly associated with the disease condition. Multifactor dimensionality reduction analysis further substantiated that the three-allele model influences the outcome of the phenotype highlighting the effect of modifiers in the etiology of LQTS.As HSP-70 influences the channel assembly and maturation/trafficking of the ion channel proteins, the alleles C of the HSP-70-1 and G of the HSP-70-2 loci and the haplotype group C-G-T could be considered a diagnostic biomarker in the identification of the LQTS phenotype with a potential to affect the progression and modification of the disease phenotype.