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ACE2, CALM3 and TNNI3K polymorphisms as potential disease modifiers in hypertrophic and dilated cardiomyopathies

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A Correction to this article was published on 28 November 2018

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Abstract

The marked clinical and genetic heterogeneity seen in hypertrophic (HCM) and dilated cardiomyopathies (DCM) suggests involvement of disease modifiers and environmental factors in the pathophysiology of these diseases. In the current study, we examined association of single nucleotide polymorphisms (SNPs) of three candidate genes, ACE2 (rs6632677), TNNI3K (rs49812611) and CALM3 (rs13477425) with clinical phenotypes of HCM and DCM patients of North Indian ethnicity. Prevalence of ACE2 (7160726 C>G) variant genotypes (CG and GG) was significantly higher in DCM subjects as compared to controls. Prevalence of TNNI3K (3784 C>T) and CALM3 (−34T>A) variant homozygous genotype were significantly higher in HCM and DCM subjects as compared to controls. DCM patients with CT genotype showed significant decrease in LVEF as compared to CC genotype (p < 0.03). There was significant gene–gene interaction between these SNPs and three-way SNP combination of ACE2 C>G, TNN13K C>T, CALM3 A>T gene variants and was associated with high risk of HCM and DCM. Presence of ACE2 (7160726 C>G) and CALM3 (−34T>A) variant genotypes in HCM Patients with mutations (sarcomeric or non sarcomeric genes) was associated with increased mean septal thickness, further suggesting a role of these gene variants in modifying disease phenotype. Our results suggest that ACE2, TNNI3K and CALM3 polymorphisms are associated with increased risk of HCM and DCM and may act as disease modifiers of these diseases.

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Change history

  • 28 November 2018

    In the original publication of the article, the location and rs number of TNNI3K mouse SNP (3784 C>T) (rs49812611) has been mentioned inadvertently in place of its human homologue. The correct information for human SNP is rs760769780 located at position 74436534, resulting in (G>A) change in human TNNI3K gene.

  • 28 November 2018

    In the original publication of the article, the location and rs number of TNNI3K mouse SNP (3784 C>T) (rs49812611) has been mentioned inadvertently in place of its human homologue. The correct information for human SNP is rs760769780 located at position 74436534, resulting in (G>A) change in human TNNI3K gene.

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Acknowledgements

Amit Kumar received Senior Research Fellowship from Indian Council of Medical Research (ICMR), New Delhi, India.

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The authors take responsibility for all aspects of the reliability and freedom from any bias of the data presented and their discussed interpretation.

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Authors and Affiliations

  1. Department of Experimental Medicine and Biotechnology, PGIMER, Lab No 2009, Research Block B, Chandigarh, 160012, India

    Amit Kumar, Bindu Rani, Rishikesh Prasad & Madhu Khullar

  2. Department of Otolaryngology, PGIMER, Chandigarh, India

    Rajni Sharma

  3. Department of Cardiology, PGIMER, Chandigarh, India

    Ajay Bahl

  4. Department of Endocrinology, PGIMER, Chandigarh, India

    Gurjeet Kaur

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  1. Amit Kumar
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Correspondence to Madhu Khullar.

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Kumar, A., Rani, B., Sharma, R. et al. ACE2, CALM3 and TNNI3K polymorphisms as potential disease modifiers in hypertrophic and dilated cardiomyopathies. Mol Cell Biochem 438, 167–174 (2018). https://doi.org/10.1007/s11010-017-3123-9

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  • DOI: https://doi.org/10.1007/s11010-017-3123-9

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