Association of MYBPC3 Gene Polymorphism with Cardiomyopathy Susceptibility in the Jammu Region
DOI:
https://doi.org/10.52783/jns.v14.3816Keywords:
polymorphism, Jammu, Cardiomyopathy, MYBPC3Abstract
Cardiomyopathy is a multifactorial disorder caused by hereditary and environmental factors. The MYBPC3 gene produces cardiac myosin binding protein C (cMyBP-C), which is found in heart (cardiac) muscle cells. This is linked to thick filaments and plays a structural and regulatory role in the contraction of cardiomyocytes. The MYBPC3Δ25bp deletion has been linked to an increased vulnerability to cardiomyopathy. The purpose of this study was to investigate the relationship between the MYBC3 gene polymorphism and the risk of cardiomyopathy in a case-control study from the Jammu region of J&K, UT.
Method: A total of 200 subjects were enrolled for the present study, out of which 100 were clinically diagnosed cases of cardiomyopathy and 100 were healthy age matched controls. Genotyping of cases and controls for MYBPC3 polymorphism was done by using Polymerase Chain Reaction (PCR). A statistical analysis was done to ascertain the association of the above said polymorphism with the risk of cardiomyopathy in the population of Jammu region of J&K, UT.
Results: The present study revealed the significant association of MYBPC3Δ25bp (rs36212066) gene polymorphism with an increased risk of cardiomyopathy (p=0.03) in our population. The frequency of deletion allele (risk) was found to be higher in cases (10%) than in controls (2%). Further the study indicated that the MYBPC3 Δ25bp allele adds risk for the development of cardiomyopathy in our cases compared to controls [OR (95%CI)- 5.44 (1.16 to 25.52)].
Conclusion: The study found the significant association of MYBPC3 Δ25bp polymorphism with Cardiomyopathy in population of Jammu region.
Downloads
Metrics
References
Andersson, C., Schou, M., Gustafsson, F., & Torp-Pedersen, C. (2022). Alcohol intake in patients with cardiomyopathy and heart failure: consensus and controversy. Circulation: Heart Failure, 15(8), e009459.
Arif, M., Nabavizadeh, P., Song, T., Desai, D., Singh, R., Bazrafshan, S., ... & Sadayappan, S. (2020). Genetic, clinical, molecular, and pathogenic aspects of the South Asian–specific polymorphic MYBPC3 Δ25bp variant. Biophysical Reviews, 12, 1065-1084.
Behrens-Gawlik, V., Mearini, G., Gedicke-Hornung, C., Richard, P., & Carrier, L. (2014). MYBPC3 in hypertrophic cardiomyopathy: from mutation identification to RNA-based correction. PflügersArchiv-European Journal of Physiology, 466, 215-223.
Carrier, L., Bonne, G., Bahrend, E., Yu, B., Richard, P., Niel, F., ... & Schwartz, K. (1997). Organization and sequence of human cardiac myosin binding protein C gene (MYBPC3) and identification of mutations predicted to produce truncated proteins in familial hypertrophic cardiomyopathy. Circulation research, 80(3), 427-434.
Dhandapany, P. S., Sadayappan, S., Xue, Y., Powell, G. T., Rani, D. S., Nallari, P., ... & Thangaraj, K. (2009). A common MYBPC3 (cardiac myosin binding protein C) variant associated with cardiomyopathies in South Asia. Nature genetics, 41(2), 187-191.
Flavigny, J., Robert, P., Camelin, J. C., Schwartz, K., Carrier, L., & Berrebi-Bertrand, I. (2003). Biomolecular interactions between human recombinant β-MyHC and cMyBP-Cs implicated in familial hypertrophic cardiomyopathy. Cardiovascular research, 60(2), 388-396.
Gerull, B., Klaassen, S., & Brodehl, A. (2019). The genetic landscape of cardiomyopathies. Genetic causes of cardiac disease, 45-91.
Geske, J. B., Ong, K. C., Siontis, K. C., Hebl, V. B., Ackerman, M. J., Hodge, D. O., ... & Ommen, S. R. (2017). Women with hypertrophic cardiomyopathy have worse survival. European heart journal, 38(46), 3434-3440.
Golbus, J. R., Puckelwartz, M. J., Fahrenbach, J. P., Dellefave-Castillo, L. M., Wolfgeher, D., & McNally, E. M. (2012). Population-based variation in cardiomyopathy genes. Circulation: Cardiovascular Genetics, 5(4), 391-399.
Haas, J., Frese, K. S., Peil, B., Kloos, W., Keller, A., Nietsch, R., ... & Meder, B. (2015). Atlas of the clinical genetics of human dilated cardiomyopathy. European heart journal, 36(18), 1123-1135.
Harper, A. R., Bowman, M., Hayesmoore, J. B., Sage, H., Salatino, S., Blair, E., ... & Thomson, K. L. (2020). Reevaluation of the South Asian MYBPC3 Δ25bp intronic deletion in hypertrophic cardiomyopathy. Circulation: Genomic and Precision Medicine, 13(3), e002783.
Kubo, T., Kitaoka, H., Okawa, M., Matsumura, Y., Hitomi, N., Yamasaki, N., ... & Doi, Y. L. (2005). Lifelong left ventricular remodeling of hypertrophic cardiomyopathy caused by a founder frameshift deletion mutation in the cardiac myosin-binding protein C gene among Japanese. Journal of the American College of Cardiology, 46(9), 1737-1743.
Lakdawala, N. K., Olivotto, I., Day, S. M., Han, L., Ashley, E. A., Michels, M., ... & Ho, C. Y. (2021). Associations between female sex, sarcomere variants, and clinical outcomes in hypertrophic cardiomyopathy. Circulation: Genomic and Precision Medicine, 14(1), e003062.
Leone, A., Biadi, O., &Balbarini, A. (2008). Smoking and cardiovascular system: cellular features of the damage. Current pharmaceutical design, 14(18), 1771-1777.
Niimura, H., Bachinski, L. L., Sangwatanaroj, S., Watkins, H., Chudley, A. E., McKenna, W., ... & Bjornsdottir, H. (1998). Mutations in the gene for cardiac myosin-binding protein C and late-onset familial hypertrophic cardiomyopathy. New England Journal of Medicine, 338(18), 1248-1257.
Rai, T. S., Dhandapany, P. S., Ahluwalia, T. S., Bhardwaj, M., Bahl, A., Talwar, K. K., ... & Khullar, M. (2008). ACE I/D polymorphism in Indian patients with hypertrophic cardiomyopathy and dilated cardiomyopathy. Molecular and cellular biochemistry, 311, 67-72.
Richard, P., Villard, E., Charron, P., & Isnard, R. (2006). The genetic bases of cardiomyopathies. Journal of the American College of Cardiology, 48(9S), A79-A89.
Sadayappan, S., Puckelwartz, M. J., & McNally, E. M. (2020). South Asian–Specific MYBPC3 Δ25bp Intronic Deletion and Its Role in Cardiomyopathies and Heart Failure. Circulation: Genomic and Precision Medicine, 13(3), e002986.
Shaffer, J. F., Kensler, R. W., & Harris, S. P. (2009). The myosin-binding protein C motif binds to F-actin in a phosphorylation-sensitive manner. Journal of Biological Chemistry, 284(18), 12318-12327.
United States. Public Health Service. Office of the Surgeon General, & United States. Office on Smoking. (2004). The health consequences of smoking: a report of the Surgeon General. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office of Smoking and Health.
Waldmüller, S., Sakthivel, S., Saadi, A. V., Selignow, C., Rakesh, P. G., Golubenko, M., ... & Vosberg, H. P. (2003). Novel deletions in MYH7 and MYBPC3 identified in Indian families with familial hypertrophic cardiomyopathy. Journal of molecular and cellular cardiology, 35(6), 623-636.
Watkins, H., Ashrafian, H., & Redwood, C. (2011). Inherited cardiomyopathies. New England Journal of Medicine, 364(17), 1643-1656.
Wessels, M. W., Herkert, J. C., Frohn-Mulder, I. M., Dalinghaus, M., Van Den Wijngaard, A., De Krijger, R. R., ... &Dooijes, D. (2015). Compound heterozygous or homozygous truncating MYBPC3 mutations cause lethal cardiomyopathy with features of noncompaction and septal defects. European Journal of Human Genetics, 23(7), 922-928.
Xu, Q., Dewey, S., Nguyen, S., & Gomes, A. V. (2010). Malignant and benign mutations in familial cardiomyopathies: insights into mutations linked to complex cardiovascular phenotypes. Journal of molecular and cellular cardiology, 48(5), 899-909.
Downloads
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution 4.0 International License.
You are free to:
- Share — copy and redistribute the material in any medium or format
- Adapt — remix, transform, and build upon the material for any purpose, even commercially.
Terms:
- Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
- No additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
