Subscribe to RSS
DOI: 10.1055/s-2005-858396
© Georg Thieme Verlag KG Stuttgart · New York
Genetics of Type 2 Diabetes: Impact of Interleukin-6 Gene Variants
Genetik von Typ-2-Diabetes: Einfluss von Interleukin-6-Genvarianten The KORA study group consists of H.-E. Wichmann (speaker), H. Löwel, C. Meisinger, T. Illig, R. Holle, J. John and co-workers who are responsible for the design and conduct of the KORA studies.Publication History
Publication Date:
22 July 2005 (online)
![](https://www.thieme-connect.de/media/gesu/2005S01/lookinside/thumbnails/10.1055-s-2005-858396-1.jpg)
Zusammenfassung
Die KORA-Studien bieten eine hervorragende Basis, um komplexe Erkrankungen wie Typ-2-Diabetes oder das metabolische Syndrom auf genetischer Ebene zu analysieren. In diesen Studien wurden mehr als 2000 Typ-2-Diabetiker identifiziert, von denen DNA für genetische Analysen zur Verfügung steht. Bisher stand die Analyse von Genen im Vordergrund, die an der Inflammationsantwort beteiligt sind. Interleukin-6 (IL-6) als zentraler Mediator der Akutphase-Reaktion ist von Interesse. Erhöhte IL-6-Proteinkonzentrationen im Blut können die Entstehung von Typ-2-Diabetes vorhersagen. Da der Einfluss einer DNA-Variante im Promotor des Interleukin-6-Gens bisher nicht in einer populationsbasierten Studie untersucht wurde, analysierten wir die Assoziation des Einzelnukleotidbasenaustausches (SNPs) C-174G in einer Fall-Kontroll-Studie mit 704 älteren Probanden des KORA-Surveys S4 (1999/2001). Das Allel - 174G zeigte eine Tendenz zur Assoziation mit Typ-2-Diabetes (- 174G: OR 1,20, 95 %-KI 0,90 - 1,59, p = 0,21).
Abstract
The KORA studies serve as a powerful tool for the genetic analysis of complex diseases like type 2 diabetes or the metabolic syndrome. These studies include more than 2,000 prevalent and incident type 2 diabetes cases. DNA of these patients is available to be used in genetic studies. Up to now the analyses have focussed on genes coding for proteins being involved in the inflammatory response. Interleukin-6 (IL-6) as the key mediator of the acute phase reaction is of interest. Elevated protein concentrations of IL-6 in the blood have been shown to predict type 2 diabetes. We investigated the association of the IL-6 single nucleotide polymorphism (SNP) C-174G with type 2 diabetes in a case-control study of 704 elderly participants of the KORA Survey S4 (1999/2001).
When BMI, HDL cholesterol, physical activity, hypertension, hormone replacement therapy and smoking were considered as covariables the SNP C-174G showed a trend for association with type 2 diabetes (- 174G: OR 1.20, 95 % CI 0.90 - 1.59, p = 0.21).
Schlüsselwörter
Biologische Materialien - genetische Epidemiologie - MONICA/KORA - Typ-2-Diabetes - metabolisches Syndrom
Key words
Biological materials - genetic epidemiology - MONICA/KORA - type 2 diabetes
Reference
- 1 Rathmann W, Haastert B, Icks A. et al . High prevalence of undiagnosed diabetes mellitus in Southern Germany: Target populations for efficient screening. The KORA survey 2000. Diabetologia. 2003; 46 182-189
- 2 Illig T, Bongardt F, Schöpfer A. et al . Significant association of the interleukin-6 gene polymorphisms C-174G and A-598G with type 2 diabetes. J Clin Endocr Metab. 2004; 89 5053-5058
- 3 Müller S, Martin S, Koenig W. et al . Impaired glucose tolerance is associated with increased serum concentrations of interleukin 6 and co-regulated acute-phase proteins but not TNF-alpha or its receptors. Diabetologia. 2002; 45 805-812
- 4 Pradhan A D, Manson J E, Rifai N. et al . C-reactive protein, interleukin-6, and risk of developing type 2 diabetes mellitus. JAMA. 2001; 286 327-334
- 5 Fishman D, Faulds G, Jeffery R. et al . 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 Clin Invest. 1998; 102 1369-1376
- 6 Terry C F, Loukaci V, Green F R. Cooperative influence of genetic polymorphisms on interleukin 6 transcriptional regulation. J Biol Chem. 2000; 275 18 138-18 144
- 7 Fernández-Real J M, Broch M, Vendrell J. et al . Interleukin-6 gene polymorphism and insulin sensitivity. Diabetes. 2000; 49 517-520
- 8 Kubaszek A, Pihlajamäki J, Komarovski V. et al . Promoter polymorphisms of the TNFα (G-308A) and IL-6 (C-174G) genes predict the conversion from impaired glucose tolerance to type 2 diabetes. Diabetes. 2003; 52 1872-1876
- 9 Kubaszek A, Pihlajamäki J, Punnonen K. et al . The C-174G promoter polymorphism of the IL-6 gene affects energy expenditure and insulin sensitivity. Diabetes. 2003; 52 558-561
- 10 Möhlig M, Boeing H, Spranger J. et al . Body mass index and C-174G interleukin-6 promoter polymorphism interact in predicting type 2 diabetes. J Clin Endocrinol Metab. 2004; 89 1885-1890
- 11 Stephens J W, Hurel S J, Cooper J A. et al . A common functional variant in the interleukin-6 gene is associated with increased body mass index in subjects with type 2 diabetes mellitus. Mol Genet Metab. 2004; 82 180-186
- 12 Vozarova B, Fernández-Real J M, Knowler W C. et al . The interleukin-6 (- 174) G/C promoter polymorphism is associated with type 2 diabetes mellitus in Native Americans and Caucasians. Hum Genet. 2003; 112 409-413
- 13 Jones S A, Rose-John S. The role of soluble receptors in cytokine biology: the agonistic properties of the sIL-6R/IL-6 complex. Biochim Biophys Acta. 2002; 1592 251-263
- 14 Brull D J, Montgomery H E, Sanders J. et al . Interleukin-6 gene - 174g>c and - 572g>c promoter polymorphisms are strong predictors of plasma inerleukin-6 levels after coronary artery bypass surgery. Arterioscler Thromb Vasc Biol. 2001; 21 1458-1463
- 15 Herder C, Bongardt F, Schöpfer A. et al for the KORA Study Group . Association of the interleukin-6 gene polymorphism C - 573G with circulating IL-6 concentrations and type 2 diabetes. (submitted)
- 16 Illig T, Bongardt F, Schöpfer A. et al . The endotoxin receptor TLR 4 polymorphism is not associated with diabetes or components of the metabolic syndrome. Diabetes. 2003; 52 2861-2864
- 17 Weedon M, Schwarz P, Horikawa Y. et al . Meta-analysis confirms a role for Calpain-10 variation in type 2 diabetes susceptibility. Am J Hum Gen. 2003; 73 1208-1212
- 18 Löwel H, Döring A, Schneider A. et al . The MONICA Augsburg surveys - Basis for prospective cohort studies. Gesundheitswesen. 2005; 67 S1 S13-S18
- 19 Holle R, Happich M, Löwel H. et al . KORA - A research platform for population based health research. Gesundheitswesen. 2005; 67 S1 S19-25
- 20 Wichmann H E, Gieger C, Illig T. KORA-gen: Resource for population genetics, controls and a broad spectrum of disease phenotypes. Gesundheitswesen. 2005; 67 S1 S26-S31
- 21 Löwel H, Meisinger C, Heier M. et al . The population-based Acute Myocardial Infarction (AMI) Registry of the MONICA/KORA study region of Augsburg. Gesundheitswesen. 2005; 67 S1 S31-S37
- 22 Döring A, Meisinger C, Thorand B. et al . Ernährungsverhalten und Übergewicht: Untersuchungen in den MONICA/KORA-Studien. Gesundheitswesen. 2005; 67 S1 S51-S56
- 23 Thorand B, Schneider A, Baumert J. et al . Case-Cohort study 1984 - 2002. Fall-Kohorten-Studien: Ein effektives Design zur Untersuchung von Biomarkern als Risikofaktoren für chronische Krankheiten - Darstellung am Beispiel der MONICA/KORA Augsburg Fall-Kohorten Studie 1984 - 2002. Gesundheitswesen. 2005; 67 S1 S98-S102
- 24 Meisinger C, Döring A, Heier M. et al . Type 2 Diabetes mellitus in Augsburg - an epidemiological overview. Gesundheitswesen. 2005; 67 S1 S103-S109
- 25 Rathmann W, Haastert B, Icks A. et al . The Diabetes Epidemic in the Elderly Population in Western Europe: Data from Population-Based Studies. Gesundheitswesen. 2005; 67 S1 S110-S114
- 26 Illig T, Bongardt F, Schöpfer-Wendels A. et al . Genetics of Type 2 Diabetes: Impact of Interleukin-6 Gene Variants. Gesundheitswesen. 2005; 67 S1 S122-S126
- 27 Mielck A, Reisig V, Rathmann W. Health inequalities among persons with type 2 diabetes: The example of intermittent claudication. Gesundheitswesen. 2005; 67 S1 S137-S143
- 28 Eller M, Satzinger W, Holle R. et al . Disease Management Programme in Deutschland: Erste Reaktionen der Diabetiker. Gesundheitswesen. 2005; 67 S1 S144-S149
- 29 Icks A, Rathmann W, Haastert B. et al . Cost-effectiveness of type 2 diabetes screening: Results from recently published studies. Gesundheitswesen. 2005; 67 S1 S167-S171
Dr. Thomas Illig
GSF National Research Center for Environment and Health, Institute of Epidemiology
Ingolstaedter Landstraße 1
85764 Neuherberg
Germany
Email: illig@gsf.de