Association between variations in the <it>TLR4 </it>gene and incident type 2 diabetes is modified by the ratio of total cholesterol to HDL-cholesterol
<p>Abstract</p> <p>Background</p> <p>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 inna...
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doaj-671a1db483764d319d25128277ae49d62021-04-02T08:17:57ZengBMCBMC Medical Genetics1471-23502008-02-0191910.1186/1471-2350-9-9Association between variations in the <it>TLR4 </it>gene and incident type 2 diabetes is modified by the ratio of total cholesterol to HDL-cholesterolMeisinger ChristineThorand BarbaraKlopp NormanKhuseyinova NatalieMüller MartinaBaumert JensKolz MelanieHerder ChristianKoenig WolfgangIllig Thomas<p>Abstract</p> <p>Background</p> <p>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 <it>TLR4 </it>gene and incident type 2 diabetes.</p> <p>Methods</p> <p>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 <it>TLR4 </it>gene and haplotypes were reconstructed.</p> <p>Results</p> <p>The effect of <it>TLR4 </it>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 <it>TLR4 </it>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<sup>-3</sup>). However, none of the investigated variants or haplotypes was associated with type 2 diabetes in main effect models without assessment of effect modifications.</p> <p>Conclusion</p> <p>We conclude that minor alleles of several <it>TLR4 </it>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.</p> http://www.biomedcentral.com/1471-2350/9/9 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Meisinger Christine Thorand Barbara Klopp Norman Khuseyinova Natalie Müller Martina Baumert Jens Kolz Melanie Herder Christian Koenig Wolfgang Illig Thomas |
spellingShingle |
Meisinger Christine Thorand Barbara Klopp Norman Khuseyinova Natalie Müller Martina Baumert Jens Kolz Melanie Herder Christian Koenig Wolfgang Illig Thomas Association between variations in the <it>TLR4 </it>gene and incident type 2 diabetes is modified by the ratio of total cholesterol to HDL-cholesterol BMC Medical Genetics |
author_facet |
Meisinger Christine Thorand Barbara Klopp Norman Khuseyinova Natalie Müller Martina Baumert Jens Kolz Melanie Herder Christian Koenig Wolfgang Illig Thomas |
author_sort |
Meisinger Christine |
title |
Association between variations in the <it>TLR4 </it>gene and incident type 2 diabetes is modified by the ratio of total cholesterol to HDL-cholesterol |
title_short |
Association between variations in the <it>TLR4 </it>gene and incident type 2 diabetes is modified by the ratio of total cholesterol to HDL-cholesterol |
title_full |
Association between variations in the <it>TLR4 </it>gene and incident type 2 diabetes is modified by the ratio of total cholesterol to HDL-cholesterol |
title_fullStr |
Association between variations in the <it>TLR4 </it>gene and incident type 2 diabetes is modified by the ratio of total cholesterol to HDL-cholesterol |
title_full_unstemmed |
Association between variations in the <it>TLR4 </it>gene and incident type 2 diabetes is modified by the ratio of total cholesterol to HDL-cholesterol |
title_sort |
association between variations in the <it>tlr4 </it>gene and incident type 2 diabetes is modified by the ratio of total cholesterol to hdl-cholesterol |
publisher |
BMC |
series |
BMC Medical Genetics |
issn |
1471-2350 |
publishDate |
2008-02-01 |
description |
<p>Abstract</p> <p>Background</p> <p>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 <it>TLR4 </it>gene and incident type 2 diabetes.</p> <p>Methods</p> <p>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 <it>TLR4 </it>gene and haplotypes were reconstructed.</p> <p>Results</p> <p>The effect of <it>TLR4 </it>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 <it>TLR4 </it>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<sup>-3</sup>). However, none of the investigated variants or haplotypes was associated with type 2 diabetes in main effect models without assessment of effect modifications.</p> <p>Conclusion</p> <p>We conclude that minor alleles of several <it>TLR4 </it>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.</p> |
url |
http://www.biomedcentral.com/1471-2350/9/9 |
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