title: PNPLA3as a Genetic Determinant of Risk for and Severity of Non-alcoholic Fatty Liver Disease Spectrum.
abstract: Background and Aims:Patatin-like phospholipase domain protein 3(PNPLA3) polymorphisms (rs738409C>G) are associated with non-alcoholic fatty liver disease (NAFLD). We performed a systematic review and meta-analysis to examine the association ofPNPLA3polymorphisms with the spectrum and severity of this disease.Methods:Studies evaluating the association between thePNPLA3polymorphism spectrum (fatty liver, steatohepatitis, cirrhosis, and hepatocellular carcinoma) and NAFLD were included. Pooled data are reported as odds ratios (ORs) with 95% confidence intervals.Results:Of 393 potentially relevant studies, 35 on NAFLD were included in the analysis. Compared to healthy controls, the pooled ORs forrs738409CG and GG compared to CC among patients with non-alcoholic fatty liver (NAFL) were 1.46 (1.16-1.85) and 2.76 (2.30-3.13), and were 1.75 (1.24-2.46) and 4.44 (2.92-6.76) among patients with non-alcoholic steatohepatitis respectively. The respective ORs for CG and GG compared to the CC genotype were 2.35 (0.90-6.13) and 5.05 (1.47-17.29) when comparing non-alcoholic hepatocellular carcinoma to NAFL patients. Among the NAFLD patients, the ORs for G allele frequency when comparing steatosis grade 2-3 to grade 0-1 NAFL, when comparing the NAFLD activity score of ≥ 4 to score ≤ 3, when comparing NASH to NAFLD, when comparing the presence of lobular inflammation to absence, and when comparing the presence of hepatocyte ballooning to absence were 2.33 (1.43-3.80), 1.80 (1.36-2.37), 1.66 (1.42-1.94), 1.58 (1.19-2.10), and 2.63 (1.87-3.69) respectively. Subgroup analysis based on ethnicity showed similar results.Conclusions:PNPLA3polymorphisms have strong association with the risk for and severity of NAFLDs.PNPLA3polymorphism plays an evolving role in diagnosis and treatment decisions in patients with NAFLD.
authors: Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA.
authors: Habeeb
authors: H
authors: Salameh
authors: Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA.
authors: Muhannad Al
authors: MA
authors: Hanayneh
authors: Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Iowa, Iowa City, IA, USA.
authors: Maen
authors: M
authors: Masadeh
authors: Department of Internal Medicine, University of Alabama, Birmingham, AL, USA.
authors: Mohammed
authors: M
authors: Naseemuddin
authors: Department of Internal Medicine, University of Alabama, Birmingham, AL, USA.
authors: Tasnia
authors: T
authors: Matin
authors: Genomic Medicine Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
authors: Angelika
authors: A
authors: Erwin
authors: Division of Gastroenterology and Hepatology, University of Alabama, Birmingham, AL, USA.
authors: Ashwani K
authors: AK
authors: Singal
keywords: Non-alcoholic liver disease; PNPLA3; Polymorphisms; rs738409 C>G