Identifying common genetic variations that are related to sudden cardiac death (SCD) is crucial since it can facilitate the diagnosis and risk stratification of SCD. It has been reported that COX10 mutations might be related with SCD. In this study, we performed a systematic variant screening on the COX10 to filter potential functional genetic variations. Based on the screening results, an insertion/deletion polymorphism (rs397763766) in 3'untranslated regions of COX10 was selected as the candidate variant. We conducted a case-control study to investigate the association between rs397763766 and SCD susceptibility in Chinese populations. Logistic regression analysis showed that the deletion allele of rs397763766 was associated with an increased risk for SCD (odds ratio = 1.61, 95% confidence interval = 1.25-2.07, p = 1.87 × 10-4) susceptibility than insertion allele. Further genotype-phenotype analysis using human cardiac tissue samples suggested that COX10 expression level in genotypes containing deletion allele was higher than that in ins/ins genotype. The results were further reinforced by RNA sequencing data from 1000 Genomes Project. Luciferase activity assay indicated that COX10 expression could be regulated by rs397763766 through interfering binding with miR-15b, thus conferring risk of SCD. In conclusion, the novel rs397763766 polymorphism might be a potential marker for molecular diagnosis and genetic counseling of SCD.
Keywords: COX10; SCD; genetic susceptibility; indel polymorphism; miR-15b; rs397763766.