ArticlePloS one2012
Paradoxical lower serum triglyceride levels and higher type 2 diabetes mellitus susceptibility in obese individuals with the PNPLA3 148M variant.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02783469 (Genetics of Diabetes Audit and Research in Tayside Scotland), which is not on this map. Cited by 46 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Genetics of Diabetes Audit and Research in Tayside Scotland (DOLORisk Dundee)
Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.
- Genome-wide association study of serum liver enzymes implicates diverse metabolic and liver pathology.Nature communications · 2021Pooled it
- Genome-wide scan revealed that polymorphisms in the PNPLA3, SAMM50, and PARVB genes are associated with development and progression of nonalcoholic fatty liver disease in Japan.Human genetics · 2013Trial
- Lipidomic profiles associated with treatment related hepatotoxicity in children with acute lymphoblastic leukemia.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2026Article
- Article
- Genetic Risk Factors for Metabolic Dysfunction-Associated Steatotic Liver Disease.Gut and liver · 2025Review
- Genetic susceptibility to gestational diabetes and its mild modification by bisphenol A and thyroid-stimulating hormone: findings from a South Chinese pregnancy cohort.Frontiers in nutrition · 2025Article
- U-shaped relationship between the triglyceride glucose index and the risk of incident diabetes among MASLD adults: a retrospective cohort study.Frontiers in endocrinology · 2025Article
- PNPLA3 is a triglyceride lipase that mobilizes polyunsaturated fatty acids to facilitate hepatic secretion of large-sized very low-density lipoprotein.Nature communications · 2024Article
- Associations between metabolic dysfunction-associated fatty liver disease, chronic kidney disease, and abdominal obesity: a national retrospective cohort study.Scientific reports · 2024Article
- PNPLA3 rs738409 risk genotype decouples TyG index from HOMA2-IR and intrahepatic lipid content.Cardiovascular diabetology · 2023Article
- U-shaped association between triglyceride and risk of incident diabetes in normoglycemic males with NAFLD: A population-base cohort study.International journal of medical sciences · 2023Article
- KHK, PNPLA3 and PPAR as Novel Targets for the Anti-Steatotic Action of Bempedoic Acid.Biomedicines · 2022Article
- The Coexistence of Nonalcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus.Journal of clinical medicine · 2022Review
- The genetic interactions between non-alcoholic fatty liver disease and cardiovascular diseases.Frontiers in genetics · 2022Review
- The Interplay between Insulin Resistance, Inflammation, Oxidative Stress, Base Excision Repair and Metabolic Syndrome in Nonalcoholic Fatty Liver Disease.International journal of molecular sciences · 2021Review
- Article
- The association of genetic polymorphisms with nonalcoholic fatty liver disease in a longitudinal study.BMC gastroenterology · 2020Article
- Human and molecular genetics shed lights on fatty liver disease and diabetes conundrum.Endocrinology, diabetes & metabolism · 2020Review
- Causal relationships between NAFLD, T2D and obesity have implications for disease subphenotyping.Journal of hepatology · 2020Article
- Genome-Wide Association Study of Liver Fat: The Multiethnic Cohort Adiposity Phenotype Study.Hepatology communications · 2020Article
Corrections and comments
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Authors and funding
22 authors at 6 institutions in 4 countries.
Funding
Abstract
backgroundObesity is highly associated with elevated serum triglycerides, hepatic steatosis and type 2 diabetes (T2D). The I148M (rs738409) genetic variant of patatin-like phospholipase domain-containing 3 gene (PNPLA3) is known to modulate hepatic triglyceride accumulation, leading to steatosis. No association between PNPLA3 I148M genotype and T2D in Europeans has been reported. Aim of this study is to examine the relationship between PNPLA3 I148M genotypes and serum triglycerides, insulin resistance and T2D susceptibility by testing a gene-environment interaction model with severe obesity. METHODS AND
findingsPNPLA3 I148M was genotyped in a large obese cohort, the SOS study (n = 3,473) and in the Go-DARTS (n = 15,448), a T2D case-control study. Metabolic parameters were examined across the PNPLA3 I148M genotypes in participants of the SOS study at baseline and at 2- and 10-year follow up after bariatric surgery or conventional therapy. The associations with metabolic parameters were validated in the Go-DARTS study. Serum triglycerides were found to be lower in the PNPLA3 148M carriers from the SOS study at baseline and from the Go-DARTS T2D cohort. An increased risk for T2D conferred by the 148M allele was found in the SOS study (O.R. 1.09, 95% C.I. 1.01-1.39, P = 0.040) and in severely obese individuals in the Go-DARTS study (O.R. 1.37, 95% C.I. 1.13-1.66, P = 0.001). The 148M allele was no longer associated with insulin resistance or T2D after bariatric surgery in the SOS study and no association with the 148M allele was observed in the less obese (BMI<35) individuals in the Go-DARTS study (P for interaction = 0.002). This provides evidence for the obesity interaction with I48M allele and T2D risk in a large-scale cross-sectional and a prospective interventional study.
conclusionsSeverely obese individuals carrying the PNPLA3 148M allele have lower serum triglyceride levels, are more insulin resistant and more susceptible to T2D. This study supports the hypothesis that obesity-driven hepatic lipid accumulation may contribute to T2D susceptibility.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.