IL-6 promoter polymorphism-174 is associated with new-onset diabetes after transplantation

被引:56
作者
Bamoulid, Jamal
Courivaud, Cecile
Deschamps, Marina
Mercier, Patricia
Ferrand, Christophe
Penfornis, Alfred
Tiberghien, Pierre
Chalopin, Jean-Marc
Saas, Philippe
Ducloux, Didier
机构
[1] Univ Besancon, INSERM U645, F-25030 Besancon, France
[2] CHU St Jacques, CIC Bioytherapie, Besancon, France
[3] CHU St Jacques, Dept Endocrinol, Besancon, France
来源
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2006年 / 17卷 / 08期
关键词
D O I
10.1681/ASN.2006010066
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:2333 / 2340
页数:8
相关论文
共 33 条
[1]   Nonimmunologic complications and gene polymorphisms of immunoregulatory cytokines in long-term renal transplants [J].
Babel, N ;
Cherepnev, G ;
Kowalenko, A ;
Horstrup, J ;
Volk, HD ;
Reinke, P .
KIDNEY INTERNATIONAL, 2004, 66 (01) :428-432
[2]   Interleukin-6 gene -174G > C and -572G > C promoter polymorphisms are strong predictors of plasma -: Interleukin-6 levels after coronary artery bypass surgery [J].
Brull, DJ ;
Montgomery, HE ;
Sanders, J ;
Dhamrait, S ;
Luong, L ;
Rumley, A ;
Lowe, GDO ;
Humphries, SE .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2001, 21 (09) :1458-1463
[3]   New-onset diabetes after transplantation: 2003 International Consensus Guidelines [J].
Davidson, J ;
Wilkinson, A ;
Dantal, J ;
Dotta, F ;
Haller, H ;
Hernández, D ;
Kasiske, BL ;
Kiberd, B ;
Krentz, A ;
Legendre, C ;
Marchetti, P ;
Markell, M ;
van der Woude, FJ ;
Wheeler, DC .
TRANSPLANTATION, 2003, 75 (10) :SS3-SS24
[4]   An interleukin-6 promoter variant is not associated with an increased risk for Alzheimer's disease [J].
Depboylu, C ;
Lohmüller, F ;
Gocke, P ;
Du, Y ;
Zimmer, R ;
Gasser, T ;
Klockgether, T ;
Dodel, RC .
DEMENTIA AND GERIATRIC COGNITIVE DISORDERS, 2004, 17 (03) :170-173
[5]   Lipid and carbohydrate metabolism in mice with a targeted mutation in the IL-6 gene: absence of development of age-related obesity [J].
Di Gregorio, GB ;
Hensley, L ;
Lu, T ;
Ranganathan, G ;
Kern, PA .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2004, 287 (01) :E182-E187
[6]   Posttransplant diabetes mellitus and atherosclerotic events in renal transplant recipients: A prospective study [J].
Ducloux, D ;
Kazory, A ;
Chalopin, JM .
TRANSPLANTATION, 2005, 79 (04) :438-443
[7]   CD4 cell lymphopenia and atherosclerosis in renal transplant recipients [J].
Ducloux, D ;
Challier, B ;
Saas, P ;
Tiberghien, P ;
Chalopin, JM .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2003, 14 (03) :767-772
[8]   Adipose tissue, adipokines, and inflammation [J].
Fantuzzi, G .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2005, 115 (05) :911-919
[9]   Interleukin-6 gene polymorphism and insulin sensitivity [J].
Fernández-Real, JM ;
Broch, M ;
Vendrell, J ;
Gutiérrez, C ;
Casamitjana, R ;
Pugeat, M ;
Richart, C ;
Ricart, W .
DIABETES, 2000, 49 (03) :517-520
[10]   The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis [J].
Fishman, D ;
Faulds, G ;
Jeffery, R ;
Mohamed-Ali, V ;
Yudkin, JS ;
Humphries, S ;
Woo, P .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 102 (07) :1369-1376