The candidate genes TAF5L, TCF7, PDCD1, IL6 and ICAM1 cannot be excluded from having effects in type 1 diabetes.
BACKGROUND
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, IL23R, IRF5 and CD40, for an association with type 1 diabetes. In addition, we tested seven genes, TAF5L, PDCD1, TCF7, IL12B, IL6, ICAM1 and TBX21, with published marginal or inconsistent evidence of an association with type 1 diabetes.


METHODS
We genotyped reported polymorphisms of the ten genes, nonsynonymous SNPs (nsSNPs) and, for the IL12B and IL6 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.


RESULTS
We found some evidence of associations between type 1 diabetes and TAF5L, PDCD1, TCF7 and IL6 (ORs = 1.05 - 1.13; P = 0.0291 - 4.16 x 10-4). No evidence of an association was obtained for IL12B, IRF5, IL23R, ICAM1, TBX21 and CD40, although there was some evidence of an association (OR = 1.10; P = 0.0257) from the genome-wide association study for the ICAM1 region.


CONCLUSIONS
We failed to exclude the possibility of some effect in type 1 diabetes for TAF5L, PDCD1, TCF7, IL6 and ICAM1. 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.
Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK. jason.cooper@cimr.cam.ac.uk
Jason D
JD
Cooper
Deborah J
DJ
Smyth
Rebecca
R
Bailey
Felicity
F
Payne
Kate
K
Downes
Lisa M
LM
Godfrey
Jennifer
J
Masters
Lauren R
LR
Zeitels
Adrian
A
Vella
Neil M
NM
Walker
John A
JA
Todd
D015703:Antigens, CD / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D016015:Logistic Models; D020641:Polymorphism, Single Nucleotide; D061026:Programmed Cell Death 1 Receptor; D051822:T Cell Transcription Factor 1 / Q000235:genetics; D035381:TATA-Binding Protein Associated Factors / Q000235:genetics; D035362:Transcription Factor TFIID / Q000235:genetics
D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D005819:Genetic Markers; D015850:Interleukin-6; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D051822:T Cell Transcription Factor 1; C100838:TAF5 protein, human; D035381:TATA-Binding Protein Associated Factors; C497576:TCF7 protein, human; D035362:Transcription Factor TFIID; D018799:Intercellular Adhesion Molecule-1