IDDF2022-ABS-0216 Does PNPLA3 RS738409 impact on NAFLD progression? A systematic review

BackgroundNon-alcoholic fatty liver disease (NAFLD) is an emerging health issue that affects 24% population world-wide, estimates about 75% of all chronic liver diseases, which results from excess accumulation of fat in the liver, producing a wide range of manifestation, simple fatty liver to non-alcoholic steatohepatitis (NASH), hepatic fibrosis, cirrhosis and even hepatocellular carcinoma (HCC). Single nucleotide polymorphism (SNP) rs738409 in the PNPLA3 C>G has been linked to NAFLD and its progression to severity, though the exact molecular mechanism and impact is not clear. We aimed to explore the impact of PNPLA3 rs738409 in the NAFLD development and its progression to severe disease. In addition, would also evaluate the linkage and predisposition of PNPLA3 rs738409 risk allele (G) in NAFLD over different population and ethnicity.MethodsA comprehensive search was made through Wiley online library, Google scholar, MEDLINE and PubMed search. Filters used were human trial, English language, time frame from 2008 to 2020 and search terms used were, ’PNPLA3+rs738409+gene’ and ’non-alcoholic fatty liver disease’; (PNPLA3[All Fields] AND rs738409[All Fields]) AND (’non-alcoholic fatty liver disease’[MeSH Terms] or ’non-alcoholic fatty liver disease’ [All Fields] and (’2008/01/01’[PubDate]:’2020/08/31’[PubDate])); (IDDF2022-ABS-0216 Figure 1).ResultsThe systematic review of 7 articles includes 14,154 participants of which male were 54.6% (39.5 to 82%) in intervention group and 41.5% (25 to 59%) in the control group. The mean age in the intervention group was 58.8 years (36.7 to 78.3) and 48.75 years (32.4–65.1) in the control group.Outcomes of the review suggests PNPLA3 rs738409 C>G polymorphic gene is strongly linked to NAFLD and its progression to severe disease (P1~4 at 95% CI).The presence of PNPLA3 rs738409 (G) minor allele increases the risk of NAFLD (from 0.15 to 4-fold) (HR 1.33%. 95% CI1.15–1.53, PG polymorphic gene is strongly linked to NAFLD and its progression to severe disease whereas, presence of G allele increases the risk of severity.