In this study, we report the association of the rs738407, rs738409, and rs2896019 variants of the patatin-like phospholipase domain-containing protein 3 (PNPLA3) (adiponutrin) gene with nonalcoholic steatohepatitis (NASH) (χ(2)=14.528, p=0.001; χ(2)=18.882, p=0.000; χ(2)=7.449, p=0.024, respectively) in 80 patients with NASH and 303 healthy controls. We genotyped the subjects using three polymerase chain reaction-restriction fragment length polymorphism methods developed in our laboratory. Our findings confirm the findings of the recent case-control and genome-wide association studies carried out in different populations around the world. Thus, the three variants in PNPLA3 gene may be a genetic risk factor for NASH.
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http://dx.doi.org/10.1089/gtmb.2014.0019 | DOI Listing |
Dig Liver Dis
January 2025
Department of Epidemiology, School of Public Health, Fudan University, Shanghai, PR China; Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, PR China; Shanghai Institute of Infectious Disease and Biosecurity, School of Public Health, Fudan University, Shanghai, 200032, PR China; Yiwu Research Institute, Fudan University, Yiwu, PR China. Electronic address:
Background: Steatotic liver disease (SLD) is influenced by both genetics and lifestyle factors, with lifestyle effects varying by genetic susceptibility. We aimed to evaluate gene-lifestyle interactions on SLD risk.
Methods: We included 28,215 UK Biobank participants with available data.
J Biol Chem
January 2025
Hypertension and Vascular Research Division, Department of Internal Medicine, Henry Ford Hospital, Detroit, MI, 48202; Department of Physiology, Wayne State University School of Medicine, Detroit, MI, USA 48202. Electronic address:
The storage and release of triacylglycerol (TAG) in lipid droplets (LDs) is regulated by dynamic protein interactions. α/β hydrolase domain-containing protein 5 (ABHD5; also known as CGI-58) is a membrane/LD bound protein that functions as a co-activator of Patatin Like Phospholipase Domain Containing 2 (PNPLA2; also known as Adipose triglyceride lipase, ATGL) the rate-limiting enzyme for TAG hydrolysis. The dysregulation of TAG hydrolysis is involved in various metabolic diseases such as metabolic dysfunction-associated steatotic liver disease (MASLD).
View Article and Find Full Text PDFJ Hepatol
January 2025
MASLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, La Jolla, CA, USA.
Background & Aims: A common genetic variant (rs738409) encoding isoleucine to methionine at position 148 in the PNPLA3 protein is a determinant of hepatic steatosis, inflammation, fibrosis, cirrhosis, and liver-related mortality. AZD2693 is a liver-targeted antisense oligonucleotide against PNPLA3 mRNA. We evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics in single ascending dose (SAD) and multiple ascending dose (MAD) studies.
View Article and Find Full Text PDFGut Liver
January 2025
Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore.
Metabolic dysfunction-associated steatotic liver disease (MASLD), is the most common cause of liver disease, and its burden on health systems worldwide continues to rise at an alarming rate. MASLD is a complex disease in which the interactions between susceptible genes and the environment influence the disease phenotype and severity. Advances in human genetics over the past few decades have provided new opportunities to improve our understanding of the multiple pathways involved in the pathogenesis of MASLD.
View Article and Find Full Text PDFMetabolites
December 2024
Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy.
Background/objectives: Low fasting blood lysosomal acid lipase (LAL) activity is associated with the pathogenesis of metabolic hepatic steatosis. We measured LAL activity in blood and plasma before and after an oral fat tolerance test (OFTT) in patients with metabolic-dysfunction-associated steatotic liver disease (MASLD).
Methods: Twenty-six controls and seventeen patients with MASLD but without diabetes were genotyped for the patatin-like phospholipase 3 (PNPLA3) rs738409 variant by RT-PCR and subjected to an OFTT, measuring LAL activity in blood and plasma with a fluorimetric method.
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