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Heat shock protein 70 gene polymorphisms’ influence on the electrophysiology of long QT syndrome

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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.

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Acknowledgments

Financial support from Department of Biotechnology, Government of India, New Delhi, and Maulana Azad National Fellowship, University Grants Commission, Government of India, New Delhi, is sincerely acknowledged.

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Authors and Affiliations

  1. Department of Genetics, University College of Science, Osmania University, Hyderabad, Telangana, 500007, India

    Altaf Ali, Sameera F. Qureshi, Veronica Medikare & Pratibha Nallari

  2. Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet, Hyderabad, Telangana, 500016, India

    Ananthapur Venkateshwari

  3. Care Hospital, Hyderabad, Telangana, India

    Narsimhan Calambur

  4. Krishna Institute of Medical Sciences, 1-8-31/1, Minister Road, Secunderabad, Telangana, 500 003, India

    Hygriv Rao

  5. Institute of Maternal and Child Health, Calicut Medical College, Calicut 8, Kerala, India

    M. P. Jayakrishnan

  6. Sri Jayadeva Institute of Cardiovascular Science and Research, Jayanagar 9th Block, Bannerghatta Road, Bangalore, Karnataka, 560069, India

    Jayaprakash Shenthar

  7. Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, Telangana, 500 007, India

    Kumarasamy Thangaraj

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  1. Altaf Ali
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  2. Sameera F. Qureshi
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  10. Pratibha Nallari
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Correspondence to Pratibha Nallari.

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Ali, A., Qureshi, S.F., Medikare, V. et al. Heat shock protein 70 gene polymorphisms’ influence on the electrophysiology of long QT syndrome. J Interv Card Electrophysiol 45, 119–130 (2016). https://doi.org/10.1007/s10840-015-0082-5

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  • DOI: https://doi.org/10.1007/s10840-015-0082-5

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