Recipient IL28B polymorphism is an important independent predictor of posttransplant diabetes mellitus in liver transplant patients with chronic hepatitis C.
IL28B polymorphisms are strongly associated with response to treatment for HCV infection. IL28B acts on interferon-stimulated genes via the JAK-STAT pathway, which has been implicated in development of insulin resistance. We investigated whether IL28B polymorphisms are associated with posttransplant diabetes mellitus (DM). Consecutive HCV patients who underwent liver transplantation between 1-1995 and 1-2011 were studied. Genotyping of the polymorphism rs12979860 was performed on DNA collected from donors and recipients. Posttransplant DM was screened for by fasting blood glucoses every 1-3 months. Of 221 included patients, 69 developed posttransplant DM (31%). Twenty-two patients with recipient IL28B genotype TT (48%), 25 with IL28B genotype CT (25%) and 22 with IL28B genotype CC (29%) developed posttransplant DM. TT genotype was statistically significantly associated with posttransplant DM over time (log rank p = 0.012 for TT vs. CT and p = 0.045 for TT vs. CC). Multivariate Cox regression analysis correcting for donor age, body mass index, baseline serum glucose, baseline serum cholesterol, recipient age and treated rejection, showed that recipient IL28B genotype TT was independently associated with posttransplant DM (hazard ratio 2.51; 95% confidence interval 1.17-5.40; p = 0.011). We conclude that the risk of developing posttransplant DM is significantly increased in recipients carrying the TT polymorphism of the IL28B gene.
Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
B J
BJ
Veldt
A
A
Duarte-Rojo
A J
AJ
Thompson
K D
KD
Watt
J K
JK
Heimbach
H L
HL
Tillmann
D D
DD
Goldstein
J G
JG
McHutchison
M R
MR
Charlton
D000328:Adult; D003920:Diabetes Mellitus / Q000175:diagnosis / Q000209:etiology*; D005260:Female; D005500:Follow-Up Studies; D016174:Hepacivirus / Q000472:pathogenicity; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000235:genetics / Q000601:surgery; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011183:Postoperative Complications; D011379:Prognosis; D011446:Prospective Studies; D012367:RNA, Viral / Q000235:genetics; D000095022:Interferon Lambda
D007371:Interferon-gamma; D007372:Interferons; D007378:Interleukins; D012367:RNA, Viral; C000624353:interferon-lambda, human; D000095022:Interferon Lambda