Modifier Genes in Hypertrophic Cardiomyopathy Patients of South Indian Cohort

Advithi Rangaraju; Satyanarayana Matsa.Lova; Narasimhan Calambur; Pratibha Nallari

doi:doi:10.11648/j.ijgg.20140205.12

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Modifier Genes in Hypertrophic Cardiomyopathy Patients of South Indian Cohort

Advithi Rangaraju, Satyanarayana Matsa.Lova, Narasimhan Calambur, Pratibha Nallari

Published in International Journal of Genetics and Genomics (Volume 2, Issue 5)

Received: 25 March 2014 Accepted: 18 April 2014 Published: 10 November 2014

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Abstract

Hypertrophic cardiomyopathy is an autosomal dominant disorder, characterized by thickening of the myocardium with a variable clinical course. Mutations in 14 sarcomeric genes have been implicated resulting in phenotypic and genotypic heterogeneity. The phenotypic expression of HCM is not only determined by the sarcomeric gene mutations but the genetic predilection of an individual also account for the inter-individual variability and genes with such functional variants that affect phenotypic expression are referred to as Modifier genes. Hence genetic variants of Angiotensin converting enzyme (ACE-2), Tumor necrosis factor- alpha (TNF-α) and Heat shock protein -70 (HSP70) genes have been considered in the present study to understand their role as modifiers of HCM. The study was carried out by Genotyping of 100 HCM and 100 controls by Polymerase chain reaction based restriction fragment length polymorphism analysis. The present study revealed a significant association of the HSP70-1 and HSP70-2 polymorphisms while ACE-2 and TNF-α genes were found to be statistically insignificant. However patients with the rare/variant genotypes were observed to have stronger clinical manifestations and echocardiographic parameters. This was further confirmed by Linkage disquillibrium analysis wherein individuals with the haplotypes GCGC and GCGT seemed to have increased susceptibility to HCM. The MDR analysis revealed a synergistic interaction of TNF-α with ACE-2 and HSP70 polymorphisms indicating their modifying effect in the presence of other environmental factors. Hence the present study emphasized the role of ACE-2, TNF-α and HSP70 polymorphisms as modifiers of the phenotypic expression in conjunction with other sarcoemric mutations and single nucleotide variations.

Published in	International Journal of Genetics and Genomics (Volume 2, Issue 5)
DOI	10.11648/j.ijgg.20140205.12
Page(s)	84-91
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Hypertrophic Cardiomyopathy, Heat Shock Protein-70, Modifier Genes, Angiotensin Converting Enzyme-2, Tumor Necrosis Factor-Alpha, Linkage Disequilibrium

References

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APA Style

Advithi Rangaraju, Satyanarayana Matsa.Lova, Narasimhan Calambur, Pratibha Nallari. (2014). Modifier Genes in Hypertrophic Cardiomyopathy Patients of South Indian Cohort. International Journal of Genetics and Genomics, 2(5), 84-91. https://doi.org/10.11648/j.ijgg.20140205.12

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ACS Style

Advithi Rangaraju; Satyanarayana Matsa.Lova; Narasimhan Calambur; Pratibha Nallari. Modifier Genes in Hypertrophic Cardiomyopathy Patients of South Indian Cohort. Int. J. Genet. Genomics 2014, 2(5), 84-91. doi: 10.11648/j.ijgg.20140205.12

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AMA Style

Advithi Rangaraju, Satyanarayana Matsa.Lova, Narasimhan Calambur, Pratibha Nallari. Modifier Genes in Hypertrophic Cardiomyopathy Patients of South Indian Cohort. Int J Genet Genomics. 2014;2(5):84-91. doi: 10.11648/j.ijgg.20140205.12

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@article{10.11648/j.ijgg.20140205.12,
  author = {Advithi Rangaraju and Satyanarayana Matsa.Lova and Narasimhan Calambur and Pratibha Nallari},
  title = {Modifier Genes in Hypertrophic Cardiomyopathy Patients of South Indian Cohort},
  journal = {International Journal of Genetics and Genomics},
  volume = {2},
  number = {5},
  pages = {84-91},
  doi = {10.11648/j.ijgg.20140205.12},
  url = {https://doi.org/10.11648/j.ijgg.20140205.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijgg.20140205.12},
  abstract = {Hypertrophic cardiomyopathy is an autosomal dominant disorder, characterized by thickening of the myocardium with a variable clinical course. Mutations in 14 sarcomeric genes have been implicated resulting in phenotypic and genotypic heterogeneity. The phenotypic expression of HCM is not only determined by the sarcomeric gene mutations but the genetic predilection of an individual also account for the inter-individual variability and genes with such functional variants that affect phenotypic expression are referred to as Modifier genes. Hence genetic variants of Angiotensin converting enzyme (ACE-2), Tumor necrosis factor- alpha (TNF-α) and Heat shock protein -70 (HSP70) genes have been considered in the present study to understand their role as modifiers of HCM. The study was carried out by Genotyping of 100 HCM and 100 controls by Polymerase chain reaction based restriction fragment length polymorphism analysis. The present study revealed a significant association of the HSP70-1 and HSP70-2 polymorphisms while ACE-2 and TNF-α genes were found to be statistically insignificant. However patients with the rare/variant genotypes were observed to have stronger clinical manifestations and echocardiographic parameters. This was further confirmed by Linkage disquillibrium analysis wherein individuals with the haplotypes GCGC and GCGT seemed to have increased susceptibility to HCM. The MDR analysis revealed a synergistic interaction of TNF-α with ACE-2 and HSP70 polymorphisms indicating their modifying effect in the presence of other environmental factors.  Hence the present study emphasized the role of ACE-2, TNF-α and HSP70 polymorphisms as modifiers of the phenotypic expression in conjunction with other sarcoemric mutations and single nucleotide variations.},
 year = {2014}
}

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TY  - JOUR
T1  - Modifier Genes in Hypertrophic Cardiomyopathy Patients of South Indian Cohort
AU  - Advithi Rangaraju
AU  - Satyanarayana Matsa.Lova
AU  - Narasimhan Calambur
AU  - Pratibha Nallari
Y1  - 2014/11/10
PY  - 2014
N1  - https://doi.org/10.11648/j.ijgg.20140205.12
DO  - 10.11648/j.ijgg.20140205.12
T2  - International Journal of Genetics and Genomics
JF  - International Journal of Genetics and Genomics
JO  - International Journal of Genetics and Genomics
SP  - 84
EP  - 91
PB  - Science Publishing Group
SN  - 2376-7359
UR  - https://doi.org/10.11648/j.ijgg.20140205.12
AB  - Hypertrophic cardiomyopathy is an autosomal dominant disorder, characterized by thickening of the myocardium with a variable clinical course. Mutations in 14 sarcomeric genes have been implicated resulting in phenotypic and genotypic heterogeneity. The phenotypic expression of HCM is not only determined by the sarcomeric gene mutations but the genetic predilection of an individual also account for the inter-individual variability and genes with such functional variants that affect phenotypic expression are referred to as Modifier genes. Hence genetic variants of Angiotensin converting enzyme (ACE-2), Tumor necrosis factor- alpha (TNF-α) and Heat shock protein -70 (HSP70) genes have been considered in the present study to understand their role as modifiers of HCM. The study was carried out by Genotyping of 100 HCM and 100 controls by Polymerase chain reaction based restriction fragment length polymorphism analysis. The present study revealed a significant association of the HSP70-1 and HSP70-2 polymorphisms while ACE-2 and TNF-α genes were found to be statistically insignificant. However patients with the rare/variant genotypes were observed to have stronger clinical manifestations and echocardiographic parameters. This was further confirmed by Linkage disquillibrium analysis wherein individuals with the haplotypes GCGC and GCGT seemed to have increased susceptibility to HCM. The MDR analysis revealed a synergistic interaction of TNF-α with ACE-2 and HSP70 polymorphisms indicating their modifying effect in the presence of other environmental factors.  Hence the present study emphasized the role of ACE-2, TNF-α and HSP70 polymorphisms as modifiers of the phenotypic expression in conjunction with other sarcoemric mutations and single nucleotide variations.
VL  - 2
IS  - 5
ER  -

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Author Information

Advithi Rangaraju

Department of Genetics, Osmania University, Jamia Osmania, Hyderabad, Andhra Pradesh
Satyanarayana Matsa.Lova

Department of Genetics, Osmania University, Jamia Osmania, Hyderabad, Andhra Pradesh
Narasimhan Calambur

Cardiologist, CARE Hospitals, Hyderabad, Andhra Pradesh
Pratibha Nallari

Department of Genetics, Osmania University, Jamia Osmania, Hyderabad, Andhra Pradesh

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APA Style

Advithi Rangaraju, Satyanarayana Matsa.Lova, Narasimhan Calambur, Pratibha Nallari. (2014). Modifier Genes in Hypertrophic Cardiomyopathy Patients of South Indian Cohort. International Journal of Genetics and Genomics, 2(5), 84-91. https://doi.org/10.11648/j.ijgg.20140205.12

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ACS Style

Advithi Rangaraju; Satyanarayana Matsa.Lova; Narasimhan Calambur; Pratibha Nallari. Modifier Genes in Hypertrophic Cardiomyopathy Patients of South Indian Cohort. Int. J. Genet. Genomics 2014, 2(5), 84-91. doi: 10.11648/j.ijgg.20140205.12

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AMA Style

Advithi Rangaraju, Satyanarayana Matsa.Lova, Narasimhan Calambur, Pratibha Nallari. Modifier Genes in Hypertrophic Cardiomyopathy Patients of South Indian Cohort. Int J Genet Genomics. 2014;2(5):84-91. doi: 10.11648/j.ijgg.20140205.12

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@article{10.11648/j.ijgg.20140205.12,
  author = {Advithi Rangaraju and Satyanarayana Matsa.Lova and Narasimhan Calambur and Pratibha Nallari},
  title = {Modifier Genes in Hypertrophic Cardiomyopathy Patients of South Indian Cohort},
  journal = {International Journal of Genetics and Genomics},
  volume = {2},
  number = {5},
  pages = {84-91},
  doi = {10.11648/j.ijgg.20140205.12},
  url = {https://doi.org/10.11648/j.ijgg.20140205.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijgg.20140205.12},
  abstract = {Hypertrophic cardiomyopathy is an autosomal dominant disorder, characterized by thickening of the myocardium with a variable clinical course. Mutations in 14 sarcomeric genes have been implicated resulting in phenotypic and genotypic heterogeneity. The phenotypic expression of HCM is not only determined by the sarcomeric gene mutations but the genetic predilection of an individual also account for the inter-individual variability and genes with such functional variants that affect phenotypic expression are referred to as Modifier genes. Hence genetic variants of Angiotensin converting enzyme (ACE-2), Tumor necrosis factor- alpha (TNF-α) and Heat shock protein -70 (HSP70) genes have been considered in the present study to understand their role as modifiers of HCM. The study was carried out by Genotyping of 100 HCM and 100 controls by Polymerase chain reaction based restriction fragment length polymorphism analysis. The present study revealed a significant association of the HSP70-1 and HSP70-2 polymorphisms while ACE-2 and TNF-α genes were found to be statistically insignificant. However patients with the rare/variant genotypes were observed to have stronger clinical manifestations and echocardiographic parameters. This was further confirmed by Linkage disquillibrium analysis wherein individuals with the haplotypes GCGC and GCGT seemed to have increased susceptibility to HCM. The MDR analysis revealed a synergistic interaction of TNF-α with ACE-2 and HSP70 polymorphisms indicating their modifying effect in the presence of other environmental factors.  Hence the present study emphasized the role of ACE-2, TNF-α and HSP70 polymorphisms as modifiers of the phenotypic expression in conjunction with other sarcoemric mutations and single nucleotide variations.},
 year = {2014}
}

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TY  - JOUR
T1  - Modifier Genes in Hypertrophic Cardiomyopathy Patients of South Indian Cohort
AU  - Advithi Rangaraju
AU  - Satyanarayana Matsa.Lova
AU  - Narasimhan Calambur
AU  - Pratibha Nallari
Y1  - 2014/11/10
PY  - 2014
N1  - https://doi.org/10.11648/j.ijgg.20140205.12
DO  - 10.11648/j.ijgg.20140205.12
T2  - International Journal of Genetics and Genomics
JF  - International Journal of Genetics and Genomics
JO  - International Journal of Genetics and Genomics
SP  - 84
EP  - 91
PB  - Science Publishing Group
SN  - 2376-7359
UR  - https://doi.org/10.11648/j.ijgg.20140205.12
AB  - Hypertrophic cardiomyopathy is an autosomal dominant disorder, characterized by thickening of the myocardium with a variable clinical course. Mutations in 14 sarcomeric genes have been implicated resulting in phenotypic and genotypic heterogeneity. The phenotypic expression of HCM is not only determined by the sarcomeric gene mutations but the genetic predilection of an individual also account for the inter-individual variability and genes with such functional variants that affect phenotypic expression are referred to as Modifier genes. Hence genetic variants of Angiotensin converting enzyme (ACE-2), Tumor necrosis factor- alpha (TNF-α) and Heat shock protein -70 (HSP70) genes have been considered in the present study to understand their role as modifiers of HCM. The study was carried out by Genotyping of 100 HCM and 100 controls by Polymerase chain reaction based restriction fragment length polymorphism analysis. The present study revealed a significant association of the HSP70-1 and HSP70-2 polymorphisms while ACE-2 and TNF-α genes were found to be statistically insignificant. However patients with the rare/variant genotypes were observed to have stronger clinical manifestations and echocardiographic parameters. This was further confirmed by Linkage disquillibrium analysis wherein individuals with the haplotypes GCGC and GCGT seemed to have increased susceptibility to HCM. The MDR analysis revealed a synergistic interaction of TNF-α with ACE-2 and HSP70 polymorphisms indicating their modifying effect in the presence of other environmental factors.  Hence the present study emphasized the role of ACE-2, TNF-α and HSP70 polymorphisms as modifiers of the phenotypic expression in conjunction with other sarcoemric mutations and single nucleotide variations.
VL  - 2
IS  - 5
ER  -

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