Functional variants of autophagy-related genes are associated with the development of hepatocellular carcinoma

This study aims to evaluate whether genetic variants in autophagy-related genes (ATGs) affect the development of HCC.Materials and methodsWe conducted a case-control study with 986 HCC cases and 1000 healthy controls to analyze 14 functional variants of five ATGs (ATG3, ATG5, ATG10, ATG12 and ATG16L1) among a Chinese population.Key findingsWe found ATG5 rs17067724 (G vs A: OR = 0.80; 95% CI = 0.65–0.98; P = 0.031), ATG10 rs1864183 (G vs A: OR = 1.29; 95% CI = 1.07–1.57; P = 0.009), ATG10 rs10514231 (C vs T: OR = 1.41; 95% CI = 1.15–1.73; P = 0.001), ATG12 rs26537 (C vs T: OR = 1.16; 95% CI = 1.02–1.33; P = 0.030), and ATG16L1 rs4663402 (T vs A: OR = 1.28; 95% CI = 1.01–1.63; P = 0.044) were significantly associated with HCC risk. Specifically, ATG10 rs10514231 kept significant association even adjusted for Bonferroni correction (P = 0.001 × 14 = 0.014). Bioinformatics analyses showed that allele C of ATG10 rs10514231 was significantly correlated with higher expression of ATG10 gene in both HCC tissues and normal liver tissues. Dual-luciferase reporter assay presented that cell lines transfected with vectors containing the risk allele C of rs10514231 showed higher relative luciferase activity compared to that containing the allele T.SignificanceThese results suggested that ATG10 rs10514231 might contribute to an allele-specific effect on the expression of host gene ATG10 and explain a fraction o...
Source: Life Sciences - Category: Biology Source Type: research