Accuri C6 Flow Cytometer System
A more recent version of this article appeared on March 1, 2007

Published online before print January 5, 2007
This Article
Right arrow Full Text (Reprint (PDF))
Right arrow All Versions of this Article:
jlb.0906577v1
81/3/581    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Payne, F.
Right arrow Articles by Todd, J. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Payne, F.
Right arrow Articles by Todd, J. A.
© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0906577

Received for publication September 19, 2006.
Revised December 4, 2006.
Accepted for publication December 5, 2006.

Article

Interaction analysis of the CBLB and CTLA4 genes in type 1 diabetes

Felicity Payne , Jason D. Cooper , Neil M. Walker , Alex C. Lam , Luc J. Smink , Sarah Nutland , Helen E. Stevens , Jayne Hutchings , and John A. Todd @

Juvenile Diabetes Research Foundation/Wellcome Trust (JDRF/WT) Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK

@ To whom correspondence should be addressed. E-mail: john.todd{at}cimr.cam.ac.uk.


arrow
Abstract

Gene-gene interaction analyses have been suggested as a potential strategy to help identify common disease susceptibility genes. Recently, evidence of a statistical interaction between polymorphisms in two negative immunoregulatory genes, CBLB and CTLA4, has been reported in type 1 diabetes (T1D). This study, in 480 Danish families, reported an association between T1D and a synonymous coding SNP in exon 12 of the CBLB gene (rs3772534 G>A; minor allele frequency, MAF=0.24; derived relative risk, RR for G allele=1.78; P=0.046). Furthermore, evidence of a statistical interaction with the known T1D susceptibility-associated CTLA4 polymorphism rs3087243 (laboratory name CT60, G>A) was reported (P<0.0001), such that the CBLB SNP rs3772534 G allele was overtransmitted to offspring with the CTLA4 rs3087243 G/G genotype. We have, therefore, attempted to obtain additional support for this finding in both large family and case-control collections. In a primary analysis, no evidence for an association of the CBLB SNP rs3772534 with disease was found in either sample set (2082 parent-child trios, P=0.33; 3453 cases and 3655 controls, P=0.69). In the case-only statistical interaction analysis between rs3772534 and rs3087243, there was also no support for an effect (1994 T1D affected offspring, P=0.21 and 3,215 cases, P=0.92). These data highlight the need for large, well-characterized populations, offering the possibility of obtaining additional support for initial observations owing to the low prior probability of identifying reproducible evidence of gene-gene interactions in the analysis of common disease-associated variants in human populations.

Key Words: CBLB • CTLA4 • Type 1 diabetes • rs3087243 • rs3772534