Published: 2021-08-21

Study to establish genetic association of cardiac conduction defect in Indian patients undergoing pacemaker implantation

Swapnil S. Garde, Pranab J. Bhattacharyya, Mohammad Ghaznavi Idris, Romar Dabu, Gautam Hazarika


Background: The aim was to study the genetic association of cardiac conduction defects (CCDs) by evaluating single nucleotide polymorphism (SNP) in genes of SCN1B and KCNJ2 and to evaluate baseline characteristics between cases and controls.

Methods: Case group consisted of 81 individuals with diagnosis of conduction disturbances who underwent permanent pacemaker implantation. The control group consisted of 79 unrelated individuals above 18 years of age of the local population not having a present or past personal or family history (first degree relatives) of any cardiac ailment especially CCDs. Isolation of genomic deoxyribonucleic acid (DNA) from all samples was done, genomic DNA was checked to ensure the presence of intact DNA.

Results: SCN1B: SNP rs55742440 had no bearing on the protein except in producing a splice variant. SNP rs67701503 does not lie in the splice-site region, thus not having any significance in the regulation of the gene as well. NetGene2 analysis of SNP rs67486287 negates its presence in the splice site. KCNJ2:SNP rs199473653 leads to a missense amino acid change, resulting in homozygous GG variant found in almost equal frequency in both groups. SNP rs199473653 gene has not been reported as a disease causing mutation.

Conclusions: The alteration of nucleotide in SCN1B intron (SNP rs55742440, rs67701503, rs67486287) between cases and controls was found to have no odds of affecting the outcome of CCD. There was no variation or alteration in nucleotide bases of KCNJ2 (SNP rs786205813, rs199473653) between the groups.



Genetic association, Cardiac conduction defect, Pacemaker implantation

Full Text:



Park DS, Fishman GI. The cardiac conduction system. Circulation. 2011;123(8):904-15.

Michaëlsson M, Jonzon A, Riesenfeld T. Isolated congenital complete atrioventricular block in adult life. A prospective study. Circulation. 1995;92(3):442-9.

Balmer C, Fasnacht M, Rahn M, Molinari L, Bauersfeld U. Long-term follow up of children with congenital complete atrioventricular block and the impact of pacemaker therapy. Europace. 2002;4(4):345-9.

Friedlander Y, Siscovick DS, Weinmann S, Austin MA, Psaty BM, Lemaitre RN, et al. Family history as a risk factor for primary cardiac arrest. Circulation. 1998;97(2):155-60.

Jouven X, Desnos M, Guerot C, Ducimetière P. Predicting sudden death in the population: the Paris prospective study I. Circulation. 1999;99(15):1978-83.

Tan HL, Bezzina CR, Smits JP, Verkerk AO, Wilde AA. Genetic control of sodium channel function. Cardiovasc Res. 2003;57(4):961-73.

Roden DM, Balser JR, George AL, Anderson ME. Cardiac ion channels. Annu Rev Physiol. 2002;64:431-75.

Park DS, Fishman GI. The cardiac conduction system. Circulation. 2011;123(8):904-15.

Ashraf A, Mir TA, Yousuf AW, Ali G, Khan J. Cardiac conduction defects and cardiovascular risk factors -a hospital based study. Int J Adv Res. 2017;5:1200-13.

Shenthar J, Bohra S, Jetley V, Vora A, Lokhandwala Y, Nabar A, et al. A survey of cardiac implantable electronic device implantation in India: by Indian society of electrocardiology and Indian HEART RHYTHM SOCIETY. Indian Heart J. 2016;68(1):68-71.

Jain M, Kiyawat P, Kiyawat S. Clinical profiles of patients undergoing pacemaker implantation in India. J Med Sci Clinic Res. 2018;6(6):44-7.

Kanse VY, Chongtham DS, Salam KS, Nemichandra SC, Upretti S, Singh SD. Clinical profiles and outcomes of patients undergoing pacemaker implantation. J Med Soc. 2015;29:40-4.

Movahed MR. Diabetes as a risk factor for cardiac conduction defects: a review. Diabetes Obes Metab. 2007;9(3):276-81.

Jeong JH, Kim JH, Park YH, Han DC, Hwang KW, Lee DW, et al. Incidence of and risk factors for bundle branch block in adults older than 40 years. Korean J Intern Med. 2004;19(3):171-8.

Rubi DEG, Dergal EB. Bifascicular block: long-term follow-up. Report of 40 cases. Arch Inst Cardiol Mex. 1982;52:31-8.

Podlaha R, Falk A. The prevalence of diabetes mellitus and other risk factors of atherosclerosis in bradycardia requiring pacemaker treatment. Horm Metab Res Suppl. 1992;26:84-7.

Refsgaard L, Olesen MS, Møller DV, Christiansen M, Haunsø S, Svendsen VH, et al. Mutation analysis of the candidate genes SCN1B-4B, FHL1, and LMNA in patients with arrhythmogenic right ventricular cardiomyopathy. Appl Transl Genom. 2012;1:44-6.

Watanabe H, Koopmann TT, LeScouarnec S, Yang T, Ingram CR, Schott J, et al. Sodium channel β1 subunit mutations associated with Brugada syndrome and cardiac conduction disease in humans. J Clin Invest. 2008;118(6):2260-8.

Xia M, Jin Q, Bendahhou S, He Y, Larroque MM, Chen Y, et al. A Kir2.1 gain-of-function mutation underlies familial atrial fibrillation. Biochem Biophys Res Commun. 2005;332(4):1012-9.

Ellinor PT, Moore RK, Patton KK, Ruskin JN, Pollak MR, MacRae CA. Mutations in the long QT gene, KCNQ1 are an uncommon cause of atrial fibrillation. Heart. 2004;90(12):1487-8.