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Volume 43 Number 5 Volume 43 Number 6

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Research articles

ScienceAsia 43 (2017): 362-368 |doi: 10.2306/scienceasia1513-1874.2017.43.362

Gene polymorphisms of autophagy machinery and the risk of hepatitis B virus-related hepatocellular carcinoma in a Thai population

Suthida Wisetsathorna, Varangkana Tantithavorna, Nattiya Hirankarnb, Pisit Tangkijvanichc, Thammakorn Saethangd, Ingorn Kimkonga,e,*

ABSTRACT:     Most cases of hepatocellular carcinoma (HCC) are associated with hepatitis B virus (HBV) infection. Previous studies revealed that some autophagy-related genes expression was increased in the HCC cell lines and tissue samples when compared to the controls. However, the mechanism of these autophagy genes in HBV-related HCC is still unclear. Hence we aim to search for the functional single nucleotide polymorphisms (SNPs) of autophagy-related genes associated with HCC. Two hundred and sixteen Thai patients with chronic HBV (CHB) infection (102 with HCC and 114 without HCC), 91 recovered individuals, and 131 healthy controls were recruited. The PCR-RFLP method and TaqMan allelic discrimination assay were applied to analyse eight SNPs including mTOR rs2295080, ATG7 rs2305686, ATG5 rs41292420, ATG5 rs77859116, ATG5 rs510432, IGF1 rs75960260, PIK3C3 rs3813065, and ATG16L1 rs2241880. Our study found that the A allele of ATG16L1 rs2241880 was associated with an increased risk in HCC as compared to CHB patients without HCC and healthy controls (OR=1.62, P=0.033; OR=1.98, P=0.002, respectively). The T allele of ATG5 rs77859116 was significantly associated with the risk to HCC as compared with CHB patients without HCC (OR=23.61, P=0.000007). Furthermore, we found that the combination of CT (rs41292420), TT (rs77859116), and CC (rs510432) genotypes of ATG5 conferred the risk to HCC, with the OR of the high-risk to low-risk group being 16.42 and P=0.003. This study suggests that the polymorphisms of the ATG5 and ATG16L1 genes might be involved in HBV-related hepatocellular carcinogenesis in Thai. However, a functional study of these polymorphisms should be further confirmed.

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a Department of Microbiology, Faculty of Science, Kasetsart University, Bangkok 10900 Thailand
b Center of Excellence in Immunology and Immune Mediated Diseases, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330 Thailand
c Research Unit of Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University, Bangkok 10330 Thailand
d Systems Biology Center, Research Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok 10330 Thailand
e Center for Advanced Studies in Tropical Natural Resources, National Research University–Kasetsart University, Kasetsart University, Bangkok 10900 Thailand

* Corresponding author, E-mail: fsciiok@ku.ac.th

Received 16 Jul 2017, Accepted 27 Jan 2018