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Effects of interacting networks of cardiovascular risk genes on the risk of type 2 diabetes mellitus (the CODAM study).
BMC Med Genet. 2008 Apr 24; 9:36.BM

Abstract

BACKGROUND

Genetic dissection of complex diseases requires innovative approaches for identification of disease-predisposing genes. A well-known example of a human complex disease with a strong genetic component is Type 2 Diabetes Mellitus (T2DM).

METHODS

We genotyped normal-glucose-tolerant subjects (NGT; n = 54), subjects with an impaired glucose metabolism (IGM; n = 111) and T2DM (n = 142) subjects, in an assay (designed by Roche Molecular Systems) for detection of 68 polymorphisms in 36 cardiovascular risk genes. Using the single-locus logistic regression and the so-called haplotype entropy, we explored the possibility that (1) common pathways underlie development of T2DM and cardiovascular disease -which would imply enrichment of cardiovascular risk polymorphisms in "pre-diabetic" (IGM) and diabetic (T2DM) populations- and (2) that gene-gene interactions are relevant for the effects of risk polymorphisms.

RESULTS

In single-locus analyses, we showed suggestive association with disturbed glucose metabolism (i.e. subjects who were either IGM or had T2DM), or with T2DM only. Moreover, in the haplotype entropy analysis, we identified a total of 14 pairs of polymorphisms (with a false discovery rate of 0.125) that may confer risk of disturbed glucose metabolism, or T2DM only, as members of interacting networks of genes. We substantiated gene-gene interactions by showing that these interacting networks can indeed identify potential "disease-predisposing allele-combinations".

CONCLUSION

Gene-gene interactions of cardiovascular risk polymorphisms can be detected in prediabetes and T2DM, supporting the hypothesis that common pathways may underlie development of T2DM and cardiovascular disease. Thus, a specific set of risk polymorphisms, when simultaneously present, increases the risk of disease and hence is indeed relevant in the transfer of risk.

Authors+Show Affiliations

Laboratory for Metabolism and Vascular Medicine, Department of Internal Medicine/Cardiovascular Research Institute (CARIM), Maastricht University, Maastricht, The Netherlands. m.vangreevenbroek@intmed.unimaas.nlNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18433508

Citation

van Greevenbroek, Marleen M J., et al. "Effects of Interacting Networks of Cardiovascular Risk Genes On the Risk of Type 2 Diabetes Mellitus (the CODAM Study)." BMC Medical Genetics, vol. 9, 2008, p. 36.
van Greevenbroek MM, Zhang J, Kallen CJ, et al. Effects of interacting networks of cardiovascular risk genes on the risk of type 2 diabetes mellitus (the CODAM study). BMC Med Genet. 2008;9:36.
van Greevenbroek, M. M., Zhang, J., Kallen, C. J., Schiffers, P. M., Feskens, E. J., & de Bruin, T. W. (2008). Effects of interacting networks of cardiovascular risk genes on the risk of type 2 diabetes mellitus (the CODAM study). BMC Medical Genetics, 9, 36. https://doi.org/10.1186/1471-2350-9-36
van Greevenbroek MM, et al. Effects of Interacting Networks of Cardiovascular Risk Genes On the Risk of Type 2 Diabetes Mellitus (the CODAM Study). BMC Med Genet. 2008 Apr 24;9:36. PubMed PMID: 18433508.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of interacting networks of cardiovascular risk genes on the risk of type 2 diabetes mellitus (the CODAM study). AU - van Greevenbroek,Marleen M J, AU - Zhang,Jian, AU - Kallen,Carla J H van der, AU - Schiffers,Paul M H, AU - Feskens,Edith J M, AU - de Bruin,Tjerk W A, Y1 - 2008/04/24/ PY - 2007/07/12/received PY - 2008/04/24/accepted PY - 2008/4/25/pubmed PY - 2008/5/28/medline PY - 2008/4/25/entrez SP - 36 EP - 36 JF - BMC medical genetics JO - BMC Med. Genet. VL - 9 N2 - BACKGROUND: Genetic dissection of complex diseases requires innovative approaches for identification of disease-predisposing genes. A well-known example of a human complex disease with a strong genetic component is Type 2 Diabetes Mellitus (T2DM). METHODS: We genotyped normal-glucose-tolerant subjects (NGT; n = 54), subjects with an impaired glucose metabolism (IGM; n = 111) and T2DM (n = 142) subjects, in an assay (designed by Roche Molecular Systems) for detection of 68 polymorphisms in 36 cardiovascular risk genes. Using the single-locus logistic regression and the so-called haplotype entropy, we explored the possibility that (1) common pathways underlie development of T2DM and cardiovascular disease -which would imply enrichment of cardiovascular risk polymorphisms in "pre-diabetic" (IGM) and diabetic (T2DM) populations- and (2) that gene-gene interactions are relevant for the effects of risk polymorphisms. RESULTS: In single-locus analyses, we showed suggestive association with disturbed glucose metabolism (i.e. subjects who were either IGM or had T2DM), or with T2DM only. Moreover, in the haplotype entropy analysis, we identified a total of 14 pairs of polymorphisms (with a false discovery rate of 0.125) that may confer risk of disturbed glucose metabolism, or T2DM only, as members of interacting networks of genes. We substantiated gene-gene interactions by showing that these interacting networks can indeed identify potential "disease-predisposing allele-combinations". CONCLUSION: Gene-gene interactions of cardiovascular risk polymorphisms can be detected in prediabetes and T2DM, supporting the hypothesis that common pathways may underlie development of T2DM and cardiovascular disease. Thus, a specific set of risk polymorphisms, when simultaneously present, increases the risk of disease and hence is indeed relevant in the transfer of risk. SN - 1471-2350 UR - https://www.unboundmedicine.com/medline/citation/18433508/Effects_of_interacting_networks_of_cardiovascular_risk_genes_on_the_risk_of_type_2_diabetes_mellitus__the_CODAM_study__ DB - PRIME DP - Unbound Medicine ER -