ASSOCIATION BETWEEN PNPLA3 TM6SF2 HSD17B13 VARIANTS AND FATTY LIVER DISEASE IN PEOPLE WITH HIV AND HEPATOCELLULAR CARCINOMA

Abstract

Non-alcoholic fatty liver disease (NAFLD) is one of the main causes of chronic liver disease. The estimated prevalence of NAFLD in Thailand is around 24% to 67%. The most common causes of NAFLD are obesity, diabetes, and also viral infection. HIV infections are associated with NAFLD. Furthermore, NAFLD also showed an association with Hepatocellular carcinoma (HCC), about 4% to 27% of steatohepatitis with cirrhosis developed into HCC. Interestingly, Genetic risk factors also play a well-known role that involves in NAFLD such as PNPLA3, TM6SF2, and HSD17B13. The data on genetic risk factors in NAFLD with HIV and HCC is limited in Thailand. In this study, we aim to investigate the association between carriers of genetic variants of PNPLA3, TM6SF2, and HSD17B13 and the risk of NAFLD, NAFLD with HIV and HCC. Genotyping of PNPLA3 rs738409, TM6SF2 rs58542926, and HSD17B13 rs6834314 were performed in 600 blood samples including 150 samples from Healthy controls, 150 samples from NAFLD, 150 samples from NAFLD with HIV, and 150 samples from non-B non-C hepatocellular carcinoma (NBNC HCC). Patients with NAFLD, NAFLD with HIV, and NBNC HCC had an increased frequency of PNPLA3 G allele compared to Healthy control with an odd ratio 2.43 (95% CI 1.27-4.64; P=0.01), 1.99(95% CI 1.20-3.29; P=0.007), 2.32 (95% CI 1.19-4.53; P=0.01) respectively. T allele frequencies of TM6SF2 polymorphism were similar between healthy control and disease groups. The frequencies of HSD17B13 GG genotypes were significantly lower in NBNC HCC group compared with the Healthy control (OR 0.41; 95%CI 0.18-0.91, P=0.03). Conclusion These results revealed that PNPLA3 polymorphism was associated with fatty liver diseases in Thai population.