PNPLA3 Variants Specifically Confer Increased Risk for Histologic Nonalcoholic Fatty Liver Disease But Not Metabolic Disease†,‡
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UNLABELLED: Single nucleotide polymorphisms (SNPs) near 7 loci have been associated with liver function tests or with liver steatosis by magnetic resonance spectroscopy. In this study we aim to test whether these SNPs influence the risk of histologically-confirmed nonalcoholic fatty liver disease (NAFLD). We tested the association of histologic NAFLD with SNPs at 7 loci in 592 cases of European ancestry from the Nonalcoholic Steatohepatitis Clinical Research Network and 1405 ancestry-matched controls. The G allele of rs738409 in PNPLA3 was associated with increased odds of histologic NAFLD (odds ratio [OR] = 3.26, 95% confidence intervals [CI] = 2.11-7.21; P = 3.6 x 10(-43)). In a case only analysis of G allele of rs738409 in PNPLA3 was associated with a decreased risk of zone 3 centered steatosis (OR = 0.46, 95% CI = 0.36-0.58; P = 5.15 x 10(-11)). We did not observe any association of this variant with body mass index, triglyceride levels, high- and low-density lipoprotein levels, or diabetes (P > 0.05). None of the variants at the other 6 loci were associated with NAFLD. CONCLUSION: Genetic variation at PNPLA3 confers a markedly increased risk of increasingly severe histological features of NAFLD, without a strong effect on metabolic syndrome component traits.
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Mutations in periportal hepatocyte-enriched genes HSD17B13 and PNPLA3 are associated with NASH.
“Mutations in the periportal hepatocyte-enriched genes HSD17B13152 and PNPLA3153 are associated with NASH”
From Distinct hepatocyte identities in liver homeostasis and regeneration (2023) · cites this paper as [153]
The Discussion reports that the rs738409 G allele in PNPLA3 is associated with NASH. It discusses periportal hepatocytes but does not establish that PNPLA3 is enriched in them. The separate citation attached to HSD17B13 is not assessed here. (LLM, conf=0.84)
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- Authors
- Speliotes, E. K., Butler, J. L., Palmer, C. D., Voight, B. F., & Hirschhorn, J. N.
- Affiliations
- Broad Institute (US)
- Corresponding author
- Speliotes, Elizabeth K.
- Venue
- Hepatology
- Published
- 2010-09
- Volume
- 52
- Issue
- 3
- Pages
- 904-912
- ISSN
- 0270-9139 (ISSN-L)
- PMC
- PMC3070300
- OpenAlex
- W2056315356
- Cited by
- 362
- References
- 29
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 9 · 2023: 10 · 2022: 19 · 2021: 13 · 2020: 27 · 2019: 20 · 2018: 20 · 2017: 22 · 2016: 30 · 2015: 38 · 2014: 32 · 2013: 22 · 2012: 41
- FWCI
- 24.51
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Public Health Service (ULRR02413101)
- National Heart, Lung, and Blood Institute (R01HL087676)
- National Institute of Diabetes and Digestive and Kidney Diseases (U01DK061730, T32 DK07191-32, F32DK079466, K23DK080145, R01DK075787, U01DK061731, U01DK061713, U01DK061728, U01DK061737, U01DK061732, U01DK061734, U01DK061718, U01DK061738, T32DK007191)
- National Center for Research Resources (UL1RR024989, M01RR000750, UL1RR025014, M01RR020359, M01RR000065, M01RR000188, M01 RR-00188, M01RR000827)
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Nutrition, Genetics, and Disease
- Keywords
- PNPLA3, rs738409, non-alcoholic fatty liver disease, genetic susceptibility, single nucleotide polymorphisms, hepatic steatosis, metabolic syndrome, triglycerides, lipoproteins, diabetes mellitus, body mass index
- MeSH terms
- Acyltransferases, Adult, Alleles, Biopsy, Fatty Liver, Female, Humans, Lipase, Liver, Male, Membrane Proteins, Risk Factors, Severity of Illness Index, Case-Control Studies, Disease Progression, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Metabolic Syndrome, White People, Lipid Metabolism, Phospholipases A2, Calcium-Independent
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