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Horm Metab Res 2007; 39(1): 46-52
DOI: 10.1055/s-2007-957345
Original Clinical

© Georg Thieme Verlag KG Stuttgart · New York

Variants of the Transcription Factor 7-Like 2 Gene (TCF7L2) are Strongly Associated with Type 2 Diabetes but not with the Metabolic Syndrome in the MONICA/KORA Surveys

C. Marzi 2 , C. Huth 1 , 2 , M. Kolz 1 , 2 , H. Grallert 1 , C. Meisinger 1 , H.-E. Wichmann 1 , 2 , W. Rathmann 3 , C. Herder 4 [*] , T. Illig 1 [*]
  • 1GSF National Research Center for Environment and Health, Institute of Epidemiology, Neuherberg, Germany
  • 2IBE, Chair of Epidemiology, University of Munich, Munich, Germany
  • 3Institute of Biometrics and Epidemiology, German Diabetes Center, Leibniz Institute at Heinrich-Heine-University, Düsseldorf, Germany
  • 4German Diabetes Clinic, German Diabetes Center, Leibniz Institute at Heinrich-Heine-University, Düsseldorf, Germany
Further Information

Publication History

Received 19. 9. 2006

Accepted 30. 10. 2006

Publication Date:
16 January 2007 (online)

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Abstract

Recently, significant associations between common variants of the transcription factor 7-like 2 gene (TCF7L2) and type 2 diabetes have been reported. This study was designed to replicate the reported associations of the two highly correlated (r2=0.86) TCF7L2 single nucleotide polymorphisms rs12255372 and rs7903146 with type 2 diabetes in a case-control study of 2369 MONICA/KORA participants (678 cases/1691 controls from Augsburg, Germany). To further investigate the pathogenic mechanism underlying these associations, we extended our analyses to the metabolic syndrome (IDF, NCEP definitions) and its components in a population-based study comprising 1404 male and female KORA participants aged 55-74 years. Results of our analyses strongly confirmed the minor T alleles as risk variants for type 2 diabetes (rs7903146: ORTvsC [95% CI]=1.36 [1.18;1.58], p=0.00003, and rs12255372: ORTvsG [95% CI]=1.31 [1.13;1.51], p=0.0003). Moreover, the T allele at rs7903146 was inversely associated with log-transformed, HOMA-%B (β=-0.07, p=0.005) as a measure of basal insulin secretion, and log-transformed fasting insulin (β=-0.06, p=0.02). No association was found with insulin resistance (HOMA-IR) and the metabolic syndrome. These findings support replication evidence that TCF7L2 variants increase type 2 diabetes risk. TCF7L2 may primarily affect pancreatic beta cell function.

Key words

type 2 diabetes - TCF7L2 - association study - SNP - replication

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1 These two authors contributed equally to the manuscript.

Correspondence

T. Illig

Institute of Epidemiology

GSF National Research Center for Environment and Health

Ingolstaedter Landstr. 1

85764 Neuherbeg

Germany

Phone: +498931 87 42 49

Fax: +498931 87 45 67

Email: illig@gsf.de