The frequency of rs2200733 minor allele T in the study population is 21%. The genotype frequencies were observed at 61.5% (n=48) for homozygous wildtype, 35.8% (n=28) for heterozygotes and 2.5% (n=2) for homozygous mutants. The study shows the presence of the AF risk variant at a substantial frequency suggesting the considerable genetic susceptibility of the general population. An earlier study in Indo-Aryan population identified rs2200733 to be associated with lone AF. However, the frequency of rs2200733 was found at 13% in healthy controls in that population . The present study subjects hail from north and south Indian states, and due to the combination of Indo-Aryan and Indo-Dravidian populations, the results reflect that of the pan-Indian frequency.
The heritability rate for AF has been estimated to be 62% suggesting the significant role played the genetic factors. Both genetic and environmental factors contribute to the pathogenesis of AF. A strong genetic predisposition along with acquired cardiac or systemic diseases culminates in the development of AF . In a study that examined the role of rs2200733 in risk of AF recurrence, the SNP has been suggested to play an important role in the development and differentiation of atria/pulmonary veins (PV). It was also shown that patients harboring TT genotype have a larger right atrium and superior PV. The study also found that carriers of T allele had a larger diameter of superior PVs . rs2200733 is also postulated to regulate its nearest gene PITX2 . This gene has been shown to play an important role in the development of pulmonary vein myocardial sleeve and regulate signaling pathways leading to proarrhythmic changes in the left atrial myocardium and structural remodeling of the intercalated disc which is observed in AF pathophysiology [16, 17]. Many genetic variants identified by GWAS are often found in the intergenic regions which may play a regulatory role in modulating the expression of nearby genes . The intergenic SNP rs2200733 which is widely prevalent across global populations plays a crucial role in AF pathogenesis. The present study did not evaluate the association between the genetic risk variant and AF or consider other potential risk factors. AF being polygenic, future genetic studies of AF in Indian population should consider interrogating rs220733 given its considerable prevalence in Indians along with other pathogenic SNPs validated by meta-analyses [9, 19]. Developing a panel of highly prevalent risk variants in a population would enable identifying individuals who are genetically predisposed to AF followed up with counselling and advocating life style changes to prevent and lower AF related morbidities later in life.