Background With hepatocellular carcinoma (HCC) becoming a heavy disease burden in China, it is particular to reveal its pathological mechanism. Recent researches have indicated that small nucleolar RNAs (snoRNAs) may be involved in various cancers including HCC. Polymorphisms within snoRNAs may affect its function or expression level, and even its host gene, then produce series of effects related to itself or its host gene. Methods The association of the single nucleotide polymorphism (SNP) rs2305789 in SNORD105 with HCC susceptibility was evaluated in two independent case-control sets (712 HCC and 801 controls). The contribution of rs2305789 to HCC risk was investigated using case-control, genotype-phenotype correlation analysis, and functional assays. Results The SNP rs2305789 was significantly associated with a decreased risk of HCC in both case-control sets (OR = 0.80, 95% CI: 0.69-0.93, p = 0.003). Compared with the AA genotype, the GG genotype was significantly correlated with lower expression of both SNORD105 and PPAN (p < 0.01). Furthermore, the overexpressed SNORD105 up-regulated PPAN expression level (p < 0.05). Finally, the in vivo experiment showed that the overexpressed SNORD105 increased cell viability and motility in both HepG2 and Huh7 cell lines (p < 0.05). Conclusions To sum up, our results suggested that rs2305789 decreased the risk of HCC by reducing the expression of both SNORD105 and PPAN, which reduced HCC cell viability and motility.

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.

Sudden cardiac death (SCD) is referred to as sudden and unexpected death caused by cardiovascular diseases, in which a person preexisted heart disease or not. Compelling evidence indicates that SCD etiology have been predominantly affected by host genetic factors. However, how genetic variants play roles in the inherited risk component of SCD are still largely unknown. It has been reported that Desmoglein-2 (DSG2) mutations might be related to sudden death. In the present study, we used a candidate gene approach to investigate the associations between rs397729601 (a 2-base pair indel polymorphism) mapping to the 3'UTR of DSG2 with the risk of SCD. It is shown by logistic regression analysis that the risk of SCD has been significantly increased by the deletion allele of rs397729601 [odds ratio (OR) = 1.51; 95% confidence interval (CI) = 1.12-2.05; P= 0.00559]. Additional genotype-phenotype analysis was performed to evaluate the mRNA level, revealing that human myocardium tissues with the deletion allele showed higher expression of DSG2. Dual luciferase activity analysis was conducted in an in vitro reporter gene system, suggesting that DSG2 expression could be regulated by rs397729601 which interrupted the binding of miR-933-3p with DSG2. We concluded that rs397729601 may affect the expression of DSG2 through miR-933-3p regulation, contributing to SCD susceptibility. Thus, rs397729601 may be used as a potential marker for molecular diagnosis and genetic counseling of SCD. Our findings need to be validated through replication and further functional studies. (C) 2019 Elsevier B.V. All rights reserved.