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Open Access 01-12-2008 | Research article

Association between variations in the TLR4gene and incident type 2 diabetes is modified by the ratio of total cholesterol to HDL-cholesterol

Authors: Melanie Kolz, Jens Baumert, Martina Müller, Natalie Khuseyinova, Norman Klopp, Barbara Thorand, Christine Meisinger, Christian Herder, Wolfgang Koenig, Thomas Illig

Published in: BMC Medical Genetics | Issue 1/2008

Abstract

Background

Toll-like receptor 4 (TLR4), the signaling receptor for lipopolysaccharides, is an important member of the innate immunity system. Since several studies have suggested that type 2 diabetes might be associated with changes in the innate immune response, we sought to investigate the association between genetic variants in the TLR4 gene and incident type 2 diabetes.

Methods

A case-cohort study was conducted in initially healthy, middle-aged subjects from the MONICA/KORA Augsburg studies including 498 individuals with incident type 2 diabetes and 1,569 non-cases. Seven SNPs were systematically selected in the TLR4 gene and haplotypes were reconstructed.

Results

The effect of TLR4 SNPs on incident type 2 diabetes was modified by the ratio of total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C). In men, four out of seven TLR4 variants showed significant interaction with TC/HDL-C after correction for multiple testing (p < 0.01). The influence of the minor alleles of those variants on the incidence of type 2 diabetes was observed particularly for male patients with high values of TC/HDL-C. Consistent with these findings, haplotype-based analyses also revealed that the effect of two haplotypes on incident type 2 diabetes was modified by TC/HDL-C in men (p < 10^-3). However, none of the investigated variants or haplotypes was associated with type 2 diabetes in main effect models without assessment of effect modifications.

Conclusion

We conclude that minor alleles of several TLR4 variants, although not directly associated with type 2 diabetes might increase the risk for type 2 diabetes in subjects with high TC/HDL-C. Additionally, our results confirm previous studies reporting sex-related dissimilarities in the development of type 2 diabetes.

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The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2350/9/9/prepub

Title: Association between variations in the TLR4gene and incident type 2 diabetes is modified by the ratio of total cholesterol to HDL-cholesterol
Authors: Melanie Kolz
Jens Baumert
Martina Müller
Natalie Khuseyinova
Norman Klopp
Barbara Thorand
Christine Meisinger
Christian Herder
Wolfgang Koenig
Thomas Illig
Publication date: 01-12-2008
Publisher: BioMed Central
Published in: BMC Medical Genetics / Issue 1/2008
Electronic ISSN: 1471-2350
DOI: https://doi.org/10.1186/1471-2350-9-9

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Springer Medicine

Association between variations in the TLR4gene and incident type 2 diabetes is modified by the ratio of total cholesterol to HDL-cholesterol

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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