Association between an indel polymorphism within CTH and the risk of sudden cardiac death in a Chinese population

作者：Zhou, Wei; Yang, Qi; Yu, Huan; Zhang, Qing; Zou, Yan; Chen, Xuekun; Yang, Zhenzhen; Qu, Yiling; Tan, Rui; Li, Lijuan; Zhu, Shaohua; He, Yan; Luo, Bin; Gao, Yuzhen

来源：Legal Medicine, 2020, 46: 101736.

DOI：10.1016/j.legalmed.2020.101736

• Sudden cardiac death
• Cystathionine-gamma-lyase
• rs11304851
• Indel polymorphism
• Genetic susceptibility

Individuals harbouring specific genetic variations might trend towards suffering sudden cardiac death. Cystathionine-gamma-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-gamma-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-gamma-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-gamma-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.

• 单位
  苏州大学; 中山大学