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54. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie e.V. (GMDS)

Deutsche Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie

07. bis 10.09.2009, Essen

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Coronary artery calcification and its impact on validated genetic variants for type 2 diabetes, assessed in the Heinz Nixdorf Recall, a large German prospective cohort

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  • Sonali Pechlivanis - Institute for Medical Informatics, Biometry and Epidemiology, University of Duisburg-Essen, Essen
  • André Scherag - Institute for Medical Informatics, Biometry and Epidemiology, University of Duisburg-Essen, Essen
  • Thomas W. Mühleisen - Department of Genomics, Life & Brain Center, University of Bonn, Bonn
  • Stefan Möhlenkamp - West German Heart Center Essen, University Hospital, University Duisburg-Essen, Essen
  • Bernhard Horsthemke - Institute of Human Genetics, University Hospital of Essen, Essen
  • Raimund Erbel - West German Heart Center Essen, University Hospital, University Duisburg-Essen, Essen
  • Karl-Heinz Jöckel - Institute for Medical Informatics, Biometry and Epidemiology, University of Duisburg-Essen, Essen
  • Markus M. Nöthen - Department of Genomics, Life & Brain Center, University of Bonn, Bonn
  • Susanne Moebus - Institute for Medical Informatics, Biometry and Epidemiology, University of Duisburg-Essen, Essen
  • Heinz Nixdorf Recall Study Group

Deutsche Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie. 54. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie (gmds). Essen, 07.-10.09.2009. Düsseldorf: German Medical Science GMS Publishing House; 2009. Doc09gmds138

doi: 10.3205/09gmds138, urn:nbn:de:0183-09gmds1384

Published: September 2, 2009

© 2009 Pechlivanis et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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Aims/hypothesis: Recently, several genome-wide association (GWA) studies have robustly identified novel single nucleotide polymorphisms (SNP) related to type 2 diabetes (T2D). Several other studies using non-invasive electron-beam computed tomography, a method for the detection and quantification of coronary artery calcification (CAC), have found a higher CAC burden in participants with T2D. The aim of our study is to investigate the combined effect of the T2D SNPs and CAC for prevalent T2D cases in comparison with T2D-free controls in an unselected population-based cohort from Germany.

Methods: We genotyped 13 T2D SNPs in eight T2D candidate genes, including up- and downstream flanking sequences, using 4,459 participants (aged = 45-75 years; 610 (13.68%) with T2D; n males = 2225 (49.90%) with 389 (17.48%) T2D; n females = 2234 (50.10%) with 221 (9.89%) T2D) of the Heinz Nixdorf Recall Study. Odds ratios (ORs) were assessed by logistic regression models, adjusted for age, sex and in addition CAC.

Results: We observed an association between four SNPs and T2D, in particular SNPs in insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2), transcription factor 7-like 2 (TCF7L2), CDK5 regulatory subunit associated protein 1-like 1 (CDKAL1) and solute carrier family 30 (zinc transporter) (SLC30A8). ORs and p values for these associated SNPs ranged between ORs 1.16 to 1.30 and p = 0.00011 to 0.03. Interestingly, when stratified for sex, we observed these effects only in males.

Conclusions: We confirm that genetic variants in IGF2BP2, TCF7L2, CDKAL1 and SLC30A8 are associated with T2D. Our result is in agreement with other studies; additionally our study is the first to show these effects separately for males and females. Furthermore, the estimators (ORs) for the genetic effects for T2D risk with involvement of CAC hardly changes, implying that these genetic variants are largely independent of CAC.