The candidate genes <it>TAF5L, TCF7, PDCD1</it>, <it>IL6 </it>and <it>ICAM1 </it>cannot be excluded from having effects in type 1 diabetes

• Main Authors: Vella Adrian (Author), Zeitels Lauren R (Author), Masters Jennifer (Author), Godfrey Lisa M (Author), Downes Kate (Author), Payne Felicity (Author), Bailey Rebecca (Author), Smyth Deborah J (Author), Cooper Jason D (Author), Walker Neil M (Author), Todd John A (Author)
• Format: Book
• Published: BMC, 2007-11-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

<p>Abstract</p> <p>Background</p> <p>As genes associated with immune-mediated diseases have an increased prior probability of being associated with other immune-mediated diseases, we tested three such genes, <it>IL23R</it>, <it>IRF5 </it>and <it>CD40</it>, for an association with type 1 diabetes. In addition, we tested seven genes, <it>TAF5L</it>, <it>PDCD1, TCF7, IL12B</it>, <it>IL6</it>, <it>ICAM1 </it>and <it>TBX21</it>, with published marginal or inconsistent evidence of an association with type 1 diabetes.</p> <p>Methods</p> <p>We genotyped reported polymorphisms of the ten genes, nonsynonymous SNPs (nsSNPs) and, for the <it>IL12B </it>and <it>IL6 </it>regions, tag SNPs in up to 7,888 case, 8,858 control and 3,142 parent-child trio samples. In addition, we analysed data from the Wellcome Trust Case Control Consortium genome-wide association study to determine whether there was any further evidence of an association in each gene region.</p> <p>Results</p> <p>We found some evidence of associations between type 1 diabetes and <it>TAF5L</it>, <it>PDCD1</it>, <it>TCF7 </it>and <it>IL6 </it>(ORs = 1.05 - 1.13; <it>P </it>= 0.0291 - 4.16 × 10^-4). No evidence of an association was obtained for <it>IL12B</it>, <it>IRF5</it>, <it>IL23R, ICAM1, TBX21 </it>and <it>CD40</it>, although there was some evidence of an association (OR = 1.10; <it>P </it>= 0.0257) from the genome-wide association study for the <it>ICAM1 </it>region.</p> <p>Conclusion</p> <p>We failed to exclude the possibility of some effect in type 1 diabetes for <it>TAF5L</it>, <it>PDCD1</it>, <it>TCF7</it>, <it>IL6 </it>and <it>ICAM1</it>. Additional studies, of these and other candidate genes, employing much larger sample sizes and analysis of additional polymorphisms in each gene and its flanking region will be required to ascertain their contributions to type 1 diabetes susceptibility.</p>

Item Description

10.1186/1471-2350-8-71
1471-2350