Interactions of allelic variance of PNPLA3 with nongenetic factors in predicting nonalcoholic steatohepatitis and nonhepatic complications of severe obesity

M. M J Guichelaar, Samer Gawrieh, M. Olivier, K. Viker, A. Krishnan, S. Sanderson, M. Malinchoc, K. D. Watt, J. M. Swain, M. Sarr, M. R. Charlton

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1935-1941
Number of pages7
JournalObesity
Volume21
Issue number9
DOIs
StatePublished - Sep 2013
Externally publishedYes

Fingerprint

Morbid Obesity
Obesity
Liver
Bariatric Surgery
Phospholipases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Liver Cirrhosis
C-Reactive Protein
Insulin Resistance
Histology
Fibrosis
Alleles
Genotype
Prospective Studies
Biopsy
Glucose
Population

ASJC Scopus subject areas

  • Endocrinology
  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cite this

Interactions of allelic variance of PNPLA3 with nongenetic factors in predicting nonalcoholic steatohepatitis and nonhepatic complications of severe obesity. / Guichelaar, M. M J; Gawrieh, Samer; Olivier, M.; Viker, K.; Krishnan, A.; Sanderson, S.; Malinchoc, M.; Watt, K. D.; Swain, J. M.; Sarr, M.; Charlton, M. R.

In: Obesity, Vol. 21, No. 9, 09.2013, p. 1935-1941.

Research output: Contribution to journalArticle

Guichelaar, MMJ, Gawrieh, S, Olivier, M, Viker, K, Krishnan, A, Sanderson, S, Malinchoc, M, Watt, KD, Swain, JM, Sarr, M & Charlton, MR 2013, 'Interactions of allelic variance of PNPLA3 with nongenetic factors in predicting nonalcoholic steatohepatitis and nonhepatic complications of severe obesity', Obesity, vol. 21, no. 9, pp. 1935-1941. https://doi.org/10.1002/oby.20327
Guichelaar, M. M J ; Gawrieh, Samer ; Olivier, M. ; Viker, K. ; Krishnan, A. ; Sanderson, S. ; Malinchoc, M. ; Watt, K. D. ; Swain, J. M. ; Sarr, M. ; Charlton, M. R. / Interactions of allelic variance of PNPLA3 with nongenetic factors in predicting nonalcoholic steatohepatitis and nonhepatic complications of severe obesity. In: Obesity. 2013 ; Vol. 21, No. 9. pp. 1935-1941.
@article{80fdf5cd83ad4515a97dec26bee47ee6,
title = "Interactions of allelic variance of PNPLA3 with nongenetic factors in predicting nonalcoholic steatohepatitis and nonhepatic complications of severe obesity",
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.",
author = "Guichelaar, {M. M J} and Samer Gawrieh and M. Olivier and K. Viker and A. Krishnan and S. Sanderson and M. Malinchoc and Watt, {K. D.} and Swain, {J. M.} and M. Sarr and Charlton, {M. R.}",
year = "2013",
month = "9",
doi = "10.1002/oby.20327",
language = "English (US)",
volume = "21",
pages = "1935--1941",
journal = "Obesity",
issn = "1930-7381",
publisher = "Wiley-Blackwell",
number = "9",

}

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, Samer

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.

PY - 2013/9

Y1 - 2013/9

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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84884909122&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84884909122&partnerID=8YFLogxK

U2 - 10.1002/oby.20327

DO - 10.1002/oby.20327

M3 - Article

C2 - 23418085

AN - SCOPUS:84884909122

VL - 21

SP - 1935

EP - 1941

JO - Obesity

JF - Obesity

SN - 1930-7381

IS - 9

ER -