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A gene variant of PNPLA3, but not of APOC3, is associated with histological parameters of NAFLD in an obese population.
Obesity (Silver Spring) 2013; 21(10):2138-45O

Abstract

OBJECTIVE

Mechanisms explaining the relationship in non-alcoholic fatty liver disease (NAFLD), obesity, and insulin resistance are poorly understood. A genetic basis has been suggested. We studied the association between the genes patatin-like phospholipase domain-containing protein 3 (PNPLA3) and apolipoprotein C3 (APOC3) and metabolic and histological parameters of NAFLD in obese patients.

DESIGN AND METHODS

Overweight and obese patients underwent a metabolic and liver assessment. If NAFLD was suspected, liver biopsy was proposed. APOC3 variant rs2854117 and PNPLA3 variant rs738409 were genotyped.

RESULTS

Four hundred seventy patients were included (61.1% had liver biopsy). The percentage of patients with non-alcoholic steatohepatitis (NASH) was significantly different according to the PNPLA3 variant. After adjustment for age and body mass index, the PNPLA3 variant was associated with alanine aminotransferase (P < 0.001) and aspartate aminotransferase (P < 0.001). The PNPLA3 variant was associated with more severe features of steatohepatitis: steatosis (P < 0.001), lobular inflammation (P < 0.001), and ballooning (P = 0.002), but not with liver fibrosis, anthropometry, or insulin resistance. No significant difference in liver histology, anthropometric, or metabolic parameters was found between carriers and non-carriers of the APOC3 variant.

CONCLUSIONS

PNPLA3 polymorphism rs738409 was associated with NASH and the severity of necroinflammatory changes independently of metabolic factors. No association between APOC3 gene variant rs2854117 and histological or metabolic parameters of NAFLD was found.

Authors+Show Affiliations

Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, University of Antwerp, Belgium.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23512881

Citation

Verrijken, A, et al. "A Gene Variant of PNPLA3, but Not of APOC3, Is Associated With Histological Parameters of NAFLD in an Obese Population." Obesity (Silver Spring, Md.), vol. 21, no. 10, 2013, pp. 2138-45.
Verrijken A, Beckers S, Francque S, et al. A gene variant of PNPLA3, but not of APOC3, is associated with histological parameters of NAFLD in an obese population. Obesity (Silver Spring). 2013;21(10):2138-45.
Verrijken, A., Beckers, S., Francque, S., Hilden, H., Caron, S., Zegers, D., ... Van Gaal, L. (2013). A gene variant of PNPLA3, but not of APOC3, is associated with histological parameters of NAFLD in an obese population. Obesity (Silver Spring, Md.), 21(10), pp. 2138-45. doi:10.1002/oby.20366.
Verrijken A, et al. A Gene Variant of PNPLA3, but Not of APOC3, Is Associated With Histological Parameters of NAFLD in an Obese Population. Obesity (Silver Spring). 2013;21(10):2138-45. PubMed PMID: 23512881.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A gene variant of PNPLA3, but not of APOC3, is associated with histological parameters of NAFLD in an obese population. AU - Verrijken,A, AU - Beckers,S, AU - Francque,S, AU - Hilden,H, AU - Caron,S, AU - Zegers,D, AU - Ruppert,M, AU - Hubens,G, AU - Van Marck,E, AU - Michielsen,P, AU - Staels,B, AU - Taskinen,M-R, AU - Van Hul,W, AU - Van Gaal,L, Y1 - 2013/06/06/ PY - 2012/04/26/received PY - 2012/10/18/revised PY - 2012/12/28/accepted PY - 2013/3/21/entrez PY - 2013/3/21/pubmed PY - 2014/5/7/medline SP - 2138 EP - 45 JF - Obesity (Silver Spring, Md.) JO - Obesity (Silver Spring) VL - 21 IS - 10 N2 - OBJECTIVE: Mechanisms explaining the relationship in non-alcoholic fatty liver disease (NAFLD), obesity, and insulin resistance are poorly understood. A genetic basis has been suggested. We studied the association between the genes patatin-like phospholipase domain-containing protein 3 (PNPLA3) and apolipoprotein C3 (APOC3) and metabolic and histological parameters of NAFLD in obese patients. DESIGN AND METHODS: Overweight and obese patients underwent a metabolic and liver assessment. If NAFLD was suspected, liver biopsy was proposed. APOC3 variant rs2854117 and PNPLA3 variant rs738409 were genotyped. RESULTS: Four hundred seventy patients were included (61.1% had liver biopsy). The percentage of patients with non-alcoholic steatohepatitis (NASH) was significantly different according to the PNPLA3 variant. After adjustment for age and body mass index, the PNPLA3 variant was associated with alanine aminotransferase (P < 0.001) and aspartate aminotransferase (P < 0.001). The PNPLA3 variant was associated with more severe features of steatohepatitis: steatosis (P < 0.001), lobular inflammation (P < 0.001), and ballooning (P = 0.002), but not with liver fibrosis, anthropometry, or insulin resistance. No significant difference in liver histology, anthropometric, or metabolic parameters was found between carriers and non-carriers of the APOC3 variant. CONCLUSIONS: PNPLA3 polymorphism rs738409 was associated with NASH and the severity of necroinflammatory changes independently of metabolic factors. No association between APOC3 gene variant rs2854117 and histological or metabolic parameters of NAFLD was found. SN - 1930-739X UR - https://www.unboundmedicine.com/medline/citation/23512881/A_gene_variant_of_PNPLA3_but_not_of_APOC3_is_associated_with_histological_parameters_of_NAFLD_in_an_obese_population_ L2 - https://doi.org/10.1002/oby.20366 DB - PRIME DP - Unbound Medicine ER -