Interactions of allelic variance of PNPLA3 with nongenetic factors in predicting nonalcoholic steatohepatitis and nonhepatic complications of severe obesity
| Autor: | M M J, Guichelaar, S, Gawrieh, M, Olivier, K, Viker, A, Krishnan, S, Sanderson, M, Malinchoc, K D, Watt, J M, Swain, M, Sarr, M R, Charlton |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Blood Glucose Male Genotype Fibrinogen Genetic Variation Membrane Proteins Lipase Middle Aged Fibrosis Article Obesity Morbid Fatty Liver C-Reactive Protein Diabetes Mellitus Type 1 Liver Non-alcoholic Fatty Liver Disease Risk Factors Multivariate Analysis Humans Female Prospective Studies Insulin Resistance Alleles |
| Zdroj: | Obesity (Silver Spring, Md.). 21(9) |
| ISSN: | 1930-739X |
| Popis: | 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.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.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 (P0.05) 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-18145 IU/l, glucose100 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.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. |
| Databáze: | OpenAIRE |
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