IL-6 Promoter Polymorphism −174 Is Associated with New-Onset Diabetes after Transplantation

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 (G3C) 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.

A Polymorphism in the Zinc Transporter Gene SLC30A8 Confers Resistance Against Posttransplantation Diabetes Mellitus in Renal Allograft Recipients

“…A number of risk factors for PTDM have been reported, including older age, ethnicity, obesity, family history of diabetes, cadaver donor, frequent acute rejection, hepatitis C infection, corticosteroid dose, and type of immunosuppressant therapy (2,6 -12). However, there are few studies on genetic risk factors for the development of PTDM (13,14).…”

Immune Monitoring of Kidney Recipients: Biomarkers to Appreciate Immunosuppression -Associated Complications

“…For instance, we analyzed SNP in the IL-6 or COX-2 promoter gene (Bamoulid et al, 2006;Courivaud et al, 2009a;Courivaud et al, 2009b;Aubin et al, 2010). We correlated IL-6 promoter gene SNP at position -174 with NODAT in overweight patients (Bamoulid et al, 2006). We reported, as already published in the general population (Fishman et al, 1998), that renal transplant recipients carrying the G allele (GG or GC genotype carriers) produce higher levels of IL-6 and exhibit higher levels of CRP (Bamoulid et al, 2006).…”

“…In this setting, this promoter gene region regulates the levels of gene "production". For instance, we analyzed SNP in the IL-6 or COX-2 promoter gene (Bamoulid et al, 2006;Courivaud et al, 2009a;Courivaud et al, 2009b;Aubin et al, 2010). We correlated IL-6 promoter gene SNP at position -174 with NODAT in overweight patients (Bamoulid et al, 2006).…”

Association of leptin receptor gene polymorphisms with post-transplant diabetes mellitus: Short report and literature review

“…In the last decade, numerous other genetic studies for PTDM have been conducted in renal transplant recipients, and nearly 50 loci have been established as suspected loci (Table 4) [7][8][9][10]13,[22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41]. Polymorphisms in AIPOQ, CAPN10, CDKAL1, CDKN2A/B, HHEX, KCN11, KCNQ1, SLC30A8, and TCFL2 are known to be associated with T2DM.…”