Molecular and Cellular Biochemistry

, Volume 438, Issue 1–2, pp 167–174 | Cite as

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

  • Amit Kumar
  • Bindu Rani
  • Rajni Sharma
  • Gurjeet Kaur
  • Rishikesh Prasad
  • Ajay Bahl
  • Madhu KhullarEmail author


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.


Idiopathic cardiomyopathies ACE2 TNNI3K CALM3 Single nucleotide polymorphisms Hypertrophy modifier genes 



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

Statement of authorship

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

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Amit Kumar
    • 1
  • Bindu Rani
    • 1
  • Rajni Sharma
    • 2
  • Gurjeet Kaur
    • 4
  • Rishikesh Prasad
    • 1
  • Ajay Bahl
    • 3
  • Madhu Khullar
    • 1
    Email author
  1. 1.Department of Experimental Medicine and BiotechnologyPGIMERChandigarhIndia
  2. 2.Department of OtolaryngologyPGIMERChandigarhIndia
  3. 3.Department of CardiologyPGIMERChandigarhIndia
  4. 4.Department of EndocrinologyPGIMERChandigarhIndia

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