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Interactions of allelic variance of PNPLA3 with nongenetic factors in predicting nonalcoholic steatohepatitis and nonhepatic complications of severe obesity.
Obesity (Silver Spring) 2013; 21(9):1935-41O

Abstract

OBJECTIVE

Allelic variation (rs738409C→G) in adiponutrin (patatin-like phospholipase domain-containing protein 3, PNPLA3) has been associated with hepatic steatosis and liver fibrosis. The physiologic impact of the PNPLA3 G allele may be exacerbated in patients with severe obesity. In this study, we investigated the interactions of PNPLA3 rs738409 with a broad panel of metabolic and histologic characteristics of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NASH) in patients with medically complicated obesity.

DESIGN AND METHODS

Consecutive patients undergoing bariatric surgery were selected for a prospective study. They underwent extensive laboratory and histologic (liver biopsy) assessment, as well as evaluation of rs738409 polymorphism by TaqMan assay.

RESULTS

Only 12 (8.3%) of the 144 patients had normal liver histology, with 72 (50%) NASH, of whom 15 (10.4% of total patients) had fibrosis stage 2-3. PNPLA3 GG genotype correlated positively (P < 0.05) with serum levels of alanine aminotransferase (ALT), asparate aminotransferase (AST), glucose, fibrinogen, and insulin-dependent diabetes mellitus, homeostasis model assessment-insulin resistance, and presence of NASH. Multivariate analysis indicated that PNPLA3 rs738409 G versus C allele remained an (independent) risk factor for NASH, in addition to CK-18 >145 IU/l, glucose >100 mg/dl, and C-reactive protein (CRP) >0.8 mg/dl. The probability of NASH increased from 9% (no risk factor) to 82% if all four risk factors were present.

CONCLUSIONS

In this cohort of patients with medically complicated obesity, PNPLA3 rs738409 G allelic expression is associated with hepatic (NASH) and nonhepatic complications of obesity, such as insulin resistance. These novel findings may be related to a greater impact of PNPLA3 variant in magnitude and scope in patients with severe obesity than in less obese populations. Further studies are needed to characterize the nature of these associations.

Authors+Show Affiliations

Division of Gastroenterology and Hepatology, Medical Spectrum Twente, Enschede, The Netherlands; Liver Transplantation, Mayo Clinic, Rochester, Minnesota, USA.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 available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

23418085

Citation

Guichelaar, M M J., et al. "Interactions of Allelic Variance of PNPLA3 With Nongenetic Factors in Predicting Nonalcoholic Steatohepatitis and Nonhepatic Complications of Severe Obesity." Obesity (Silver Spring, Md.), vol. 21, no. 9, 2013, pp. 1935-41.
Guichelaar MM, Gawrieh S, Olivier M, et al. Interactions of allelic variance of PNPLA3 with nongenetic factors in predicting nonalcoholic steatohepatitis and nonhepatic complications of severe obesity. Obesity (Silver Spring). 2013;21(9):1935-41.
Guichelaar, M. M., Gawrieh, S., Olivier, M., Viker, K., Krishnan, A., Sanderson, S., ... Charlton, M. R. (2013). Interactions of allelic variance of PNPLA3 with nongenetic factors in predicting nonalcoholic steatohepatitis and nonhepatic complications of severe obesity. Obesity (Silver Spring, Md.), 21(9), pp. 1935-41. doi:10.1002/oby.20327.
Guichelaar MM, et al. Interactions of Allelic Variance of PNPLA3 With Nongenetic Factors in Predicting Nonalcoholic Steatohepatitis and Nonhepatic Complications of Severe Obesity. Obesity (Silver Spring). 2013;21(9):1935-41. PubMed PMID: 23418085.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interactions of allelic variance of PNPLA3 with nongenetic factors in predicting nonalcoholic steatohepatitis and nonhepatic complications of severe obesity. AU - Guichelaar,M M J, AU - Gawrieh,S, AU - Olivier,M, AU - Viker,K, AU - Krishnan,A, AU - Sanderson,S, AU - Malinchoc,M, AU - Watt,K D, AU - Swain,J M, AU - Sarr,M, AU - Charlton,M R, Y1 - 2013/05/29/ PY - 2011/10/14/received PY - 2012/11/24/accepted PY - 2013/2/19/entrez PY - 2013/2/19/pubmed PY - 2014/4/23/medline SP - 1935 EP - 41 JF - Obesity (Silver Spring, Md.) JO - Obesity (Silver Spring) VL - 21 IS - 9 N2 - OBJECTIVE: Allelic variation (rs738409C→G) in adiponutrin (patatin-like phospholipase domain-containing protein 3, PNPLA3) has been associated with hepatic steatosis and liver fibrosis. The physiologic impact of the PNPLA3 G allele may be exacerbated in patients with severe obesity. In this study, we investigated the interactions of PNPLA3 rs738409 with a broad panel of metabolic and histologic characteristics of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NASH) in patients with medically complicated obesity. DESIGN AND METHODS: Consecutive patients undergoing bariatric surgery were selected for a prospective study. They underwent extensive laboratory and histologic (liver biopsy) assessment, as well as evaluation of rs738409 polymorphism by TaqMan assay. RESULTS: Only 12 (8.3%) of the 144 patients had normal liver histology, with 72 (50%) NASH, of whom 15 (10.4% of total patients) had fibrosis stage 2-3. PNPLA3 GG genotype correlated positively (P < 0.05) with serum levels of alanine aminotransferase (ALT), asparate aminotransferase (AST), glucose, fibrinogen, and insulin-dependent diabetes mellitus, homeostasis model assessment-insulin resistance, and presence of NASH. Multivariate analysis indicated that PNPLA3 rs738409 G versus C allele remained an (independent) risk factor for NASH, in addition to CK-18 >145 IU/l, glucose >100 mg/dl, and C-reactive protein (CRP) >0.8 mg/dl. The probability of NASH increased from 9% (no risk factor) to 82% if all four risk factors were present. CONCLUSIONS: In this cohort of patients with medically complicated obesity, PNPLA3 rs738409 G allelic expression is associated with hepatic (NASH) and nonhepatic complications of obesity, such as insulin resistance. These novel findings may be related to a greater impact of PNPLA3 variant in magnitude and scope in patients with severe obesity than in less obese populations. Further studies are needed to characterize the nature of these associations. SN - 1930-739X UR - https://www.unboundmedicine.com/medline/citation/23418085/Interactions_of_allelic_variance_of_PNPLA3_with_nongenetic_factors_in_predicting_nonalcoholic_steatohepatitis_and_nonhepatic_complications_of_severe_obesity_ L2 - https://doi.org/10.1002/oby.20327 DB - PRIME DP - Unbound Medicine ER -