Investigation of PNPLA3 and IL28B Genotypes on Diabetes and Obesity After Liver Transplantation: Insight Into Mechanisms of Disease

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.