Association of South Asian-specific MYBPC3Δ25bp deletion polymorphism and cardiomyopathy: A systematic review and meta-analysis

Abstract Background Inherited cardiomyopathies are a frequent cause of heart failure. A 25-basepair deletion polymorphism MYBPC3Δ25bp (rs36212066) in the MYBPC3 gene found exclusively among individuals of South Asian ancestry, has been shown to be associated with an increased risk of cardiomyopathies. The purpose of this meta-analysis was to evaluate the pooled effect size and prevalence MYBPC3Δ25bp in patients with cardiomyopathies of South Asian ancestry. Methods and results We systematically reviewed studies published through June 2020 from Embase (Ovid), Medline and Web of Science databases. We included case-control studies (n = 4) that enrolled 1048 patients and 1279 controls in the meta-analysis of association between MYBPC3Δ25bp alleles and cardiomyopathy. Based on the random effects model the effect size quantified as pooled odds ratios (OR) suggests 3.4-fold excess risk of cardiomyopathy in individuals with MYBPC3Δ25bp variant in the dominant genetic model (95% CI =1.66–7.00, p = 0.0009). The pooled prevalence of the MYBPC3Δ25bp allele was 2.2% in controls reported from eight studies conducted in the South Asian population. Detailed systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD42018099279. Enrichment analysis showed that the MYBPC3Δ25bp deletion allele was significantly over enriched in the South Asian population by 5.12 and 7.88-fold compared to the other global populations in the 1000 Genomes and gnomAD v2.1.1 (controls) datasets, respectively. Conclusion Our study confirms the association of MYBPC3Δ25bp rs36212066 variant with increased risk of cardiomyopathies. The MYBPC3Δ25bp deletion allele may be considered a risk factor for cardiomyopathy susceptibility among the South Asian population.