title: Heat shock protein 70 gene polymorphisms' influence on the electrophysiology of long QT syndrome.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Genetics, University College of Science, Osmania University, Hyderabad, Telangana, 500007, India.
authors.forename: Altaf
authors.initials: A
authors.lastname: Ali
authors.affiliation: Department of Genetics, University College of Science, Osmania University, Hyderabad, Telangana, 500007, India.
authors.forename: Sameera F
authors.initials: SF
authors.lastname: Qureshi
authors.affiliation: Department of Genetics, University College of Science, Osmania University, Hyderabad, Telangana, 500007, India.
authors.forename: Veronica
authors.initials: V
authors.lastname: Medikare
authors.affiliation: Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet, Hyderabad, Telangana, 500016, India.
authors.forename: Ananthapur
authors.initials: A
authors.lastname: Venkateshwari
authors.affiliation: Care Hospital, Hyderabad, Telangana, India.
authors.forename: Narsimhan
authors.initials: N
authors.lastname: Calambur
authors.affiliation: Krishna Institute of Medical Sciences, 1-8-31/1, Minister Road, Secunderabad, Telangana, 500 003, India.
authors.forename: Hygriv
authors.initials: H
authors.lastname: Rao
authors.affiliation: Institute of Maternal and Child Health, Calicut Medical College, Calicut 8, Kerala, India.
authors.forename: M P
authors.initials: MP
authors.lastname: Jayakrishnan
authors.affiliation: Sri Jayadeva Institute of Cardiovascular Science and Research, Jayanagar 9th Block, Bannerghatta Road, Bangalore, Karnataka, 560069, India.
authors.forename: Jayaprakash
authors.initials: J
authors.lastname: Shenthar
authors.affiliation: Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, Telangana, 500 007, India.
authors.forename: Kumarasamy
authors.initials: K
authors.lastname: Thangaraj
authors.affiliation: Department of Genetics, University College of Science, Osmania University, Hyderabad, Telangana, 500007, India. prathinallari@yahoo.com.
authors.forename: Pratibha
authors.initials: P
authors.lastname: Nallari
mesh_terms: D000328:Adult; D017677:Age Distribution; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D007194:India / Q000453:epidemiology; D008133:Long QT Syndrome / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D012307:Risk Factors; D017678:Sex Distribution
chemical_list: D005819:Genetic Markers; D018840:HSP70 Heat-Shock Proteins
keywords: Electrophysiology; HSP-70; Haplotype; Long QT syndrome; Protein folding; SNP