Clinical TransplantationIL-6 Promoter Polymorphism −174 Is Associated with New-Onset Diabetes after TransplantationBamoulid, Jamal*, †; Courivaud, Ce[Combining Acute Accent]cile*, †; Deschamps, Marina*, ‡; Mercier, Patricia*, ‡; Ferrand, Christophe*, ‡; Penfornis, Alfred§; Tiberghien, Pierre*, ‡ , ‖; Chalopin, Jean-Marc*, † , ‖; Saas, Philippe*, ‡; Ducloux, Didier*, † , ‖ Author Information *INSERM, U645, University Besanc[COMBINING CEDILLA]on, and IFR133, †CHU Saint Jacques, Department of Nephrology, Dialysis, and Renal Transplantation, ‡EFS Bourgogne Franche-Comte[Combining Acute Accent], Plateforme de Biomonitoring, §CHU Jean Minjoz, Department of Endocrinology, and ‖CHU Saint Jacques, CIC Biothe[Combining Acute Accent]rapie, Besanc[COMBINING CEDILLA]on, France Address correspondence to: Dr. Didier Ducloux, CHU St. Jacques, 2 Place Saint Jacques, Besanc[COMBINING CEDILLA]on 25000, France. Phone: +33-38-121-8782; Fax: +33-38-121-8781; E-mail: [email protected] Accepted May 29, 2006 Received January 29, 2006 Journal of the American Society of Nephrology 17(8):p 2333-2340, August 2006. | DOI: 10.1681/ASN.2006010066 Buy Metrics Abstract New-onset diabetes after transplantation (NODAT) is a serious complication of transplantation. This study tested whether IL-6 production capacity may influence the development of NODAT in two different groups of patients. The occurrence of NODAT was analyzed with respect to IL-6 gene promoter polymorphism at position −174 (G→C) and other relevant risk factors retrospectively in 217 renal transplant recipients and prospectively in 132. A linear increase in both circulating IL-6 (P = 0.09) and C-reactive protein (an indicator of basal IL-6 secretion; P = 0.03) concentrations from the CC genotype to the GG genotype was observed. In the multivariate model, the CC genotype was associated with a decreased risk for NODAT compared with the GG genotype in the two cohorts. Homeostasis Model Assessment for Insulin Resistance also revealed lesser insulin sensitivity in the GG carriers than in the CC carriers (2.15 ± 2 versus 1.32 ± 1.03; P = 0.03). Subgroup analysis showed that the influence of IL-6 gene promoter polymorphism on the development of NODAT was restricted mostly to overweight patients. These results highly suggest that IL-6 production capacity influences the development of NODAT and that diabetes-inducing drug administration should be limited in overweight patients who carry the GG genotype. Copyright © 2006 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.