title: Investigation of PNPLA3 and IL28B genotypes on diabetes and obesity after liver transplantation: insight into mechanisms of disease.
abstract: To identify genetic risks for obesity and diabetes postliver transplantation (LT), LT recipients underwent genotyping for IL28B rs12979860 (n = 295) and PNPLA3 rs738409 (n = 205) polymorphism in both donors and recipients. The development of obesity and diabetes/impaired fasting glucose (IFG) was determined 1-5 years post-LT. Recipient PNPLA-3 genotype was independently associated with obesity (BMI > 30) at 3 years posttransplant (genotype CC 33.7%, CG 48.3% and GG 82.4%, p = 0.002), with an odds ratio (OR 2.54, CI 1.38-4.66, p = 0.003), associated with the G allele. Diabetes/IFG diagnosed within 5 years posttransplant associated with PNPLA-3 non-CC genotype (HR 1.59, 1.12-2.26, p = 0.010), but not IL28B TT genotype (HR 1.46, 0.94-2.27, p = 0.092). No genotype variable was independently predictive of diabetes/IFG. The combination of PNPLA-3 non-CC and IL28B TT genotype was associated with increased risk of diabetes/IFG compared to PNPLA-3 CC, IL28B non-TT (HR 2.64, CI 1.30-5.39, p = 0.008). Donor genotypes were not associated with any of the outcomes analyzed. In conclusion, PNPLA-3 non-CC genotype is associated with posttransplant obesity but not independently with diabetes/IFG. The lack of donor related risk suggests a peripheral rather than central mechanism of insulin resistance in liver transplant recipients.
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN.
authors.forename: K D
authors.initials: KD
authors.lastname: Watt
authors.forename: R
authors.initials: R
authors.lastname: Dierkhising
authors.forename: C
authors.initials: C
authors.lastname: Fan
authors.forename: J K
authors.initials: JK
authors.lastname: Heimbach
authors.forename: H
authors.initials: H
authors.lastname: Tillman
authors.forename: D
authors.initials: D
authors.lastname: Goldstein
authors.forename: A
authors.initials: A
authors.lastname: Thompson
authors.forename: A
authors.initials: A
authors.lastname: Krishnan
authors.forename: M R
authors.initials: MR
authors.lastname: Charlton
mesh_terms: D000328:Adult; D003920:Diabetes Mellitus / Q000235:genetics*; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008049:Lipase / Q000235:genetics*; D016031:Liver Transplantation / Q000009:adverse effects*; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D014019:Tissue Donors; D000095022:Interferon Lambda; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D007372:Interferons; D007378:Interleukins; D008049:Lipase; D008565:Membrane Proteins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
keywords: Diabetes; genetic risk; insulin resistance; liver transplant; obesity