Association between an indel polymorphism within CTH and the risk of sudden cardiac death in a Chinese population. (September 2020) - Zhou, Wei
Highlights: The rs113044851 polymorphism is significantly associated with SCD susceptibility. Genotypes of rs113044851 are correlated with protein level of CTH in human heart. The rs113044851 could regulate CTH expression through miR-1324. The rs113044851 may be used as a potential marker for molecular diagnosis of SCD. Abstract: Individuals harbouring specific genetic variations might trend towards suffering sudden cardiac death. Cystathionine-γ-lyase is one of the key enzymes of endogenous hydrogen sulfide production, and a key factor on the expression regulation of hydrogen sulfide in human heart. Compelling studies have suggested the cardioprotective effects of hydrogen sulfide, while it remains controversial whether cystathionine-γ-lyase and hydrogen sulfide are beneficial to cardiovascular diseases. In this study, we performed a candidate-gene-based study to evaluate the association of the Indel polymorphism rs113044851 within the 3′ untranslated region of Cystathionine-γ-lyase gene and risk of sudden cardiac death in a Chinese Han population. Logistic regression analysis showed that the insertion allele of rs113044851 significantly decreased the risk of sudden cardiac death [odds ratio = 0.58; 95% confidence interval:0.38–0.88; P = 0.0076]. Further genotype-phenotype association analysis indicated that the insertion allele was significantly associated with lower expression of cystathionine-γ-lyase in myocardium tissues. The subsequently in-silico predication revealed that compared with the deletion allele, the binding of the insertion allele with miR-1324 matched better. Finally, dual-luciferase activity assay validated the prediction that the gene transcriptional activity indicated by firefly luciferase activity with ins/ins genotype was lower than that with del/del genotype. In summary, our data suggested that rs113044851 might contribute to susceptibility of sudden cardiac death via regulating gene expression at post-transcriptional level. This indel has the potential to become a molecular diagnosis marker and genetic counseling of sudden cardiac death.