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Variation in the CTLA4/CD28 gene region confers an increased risk of coeliac disease.

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Publication Date
2002-03
ICR Author
Houlston, Richard
Popat, Sanjay
Author
Popat, S
Hearle, N
Hogberg, L
Braegger, CP
O'Donoghue, D
Falth-Magnusson, K
Holmes, GKT
Howdle, PD
Jenkins, H
Johnston, S
Kennedy, NP
Kumar, PJ
Logan, RFA
Marsh, MN
Mulder, CJ
Torinsson Naluai, A
Sjoberg, K
Stenhammar, L
Walters, JRF
Jewell, DP
Houlston, RS
Type
Journal Article
Metadata
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Abstract
Susceptibility to coeliac disease involves HLA and non-HLA-linked genes. The CTLA4/CD28 gene region encodes immune regulatory T-cell surface molecules and is a strong candidate as a susceptibility locus. We evaluated CTLA4/CD28 in coeliac disease by genetic linkage and association and combined our findings with published studies through a meta-analysis. 116 multiplex families were genotyped across CTLA4/CD28 using eight markers. The contribution of CTLA4/CD28 to coeliac disease was assessed by non-parametric linkage and association analyses. Seven studies were identified that had evaluated the relationship between CTLA4/CD28 and coeliac disease and a pooled analysis of data undertaken. In our study there was evidence for a relationship between variation in the CTLA4/CD28 region and coeliac disease by linkage and association analyses. However, the findings did not attain formal statistical significance (p = 0.004 and 0.039, respectively). Pooling findings with published results showed significant evidence for linkage (504 families) and association (940 families): p values, 0.0001 and 0.0014 at D2S2214, respectively, and 0.0008 and 0.0006 at D2S116, respectively. These findings suggest that variation in the CD28/CTLA4 gene region is a determinant of coeliac disease susceptibility. Dissecting the sequence variation underlying this relationship will depend on further analyses utilising denser sets of markers.
URL
https://repository.icr.ac.uk/handle/internal/1878
Collections
  • Clinical Studies
  • Genetics and Epidemiology
Version of record
10.1017/s0003480002001021
Subject
T-Lymphocytes
Chromosomes, Human, Pair 2
Humans
Celiac Disease
Genetic Predisposition to Disease
Antigens, Differentiation
Antigens, CD
Genetic Markers
Immunoconjugates
Risk
Statistics, Nonparametric
Genotype
Adolescent
Adult
Aged
Middle Aged
Child
Child, Preschool
Infant
Europe
Female
Male
Genetic Linkage
CTLA-4 Antigen
Abatacept
CD28 Antigens
Research team
Thoracic Oncology
Cancer Genomics
Language
eng
License start date
2002-03
Citation
Annals of human genetics, 2002, 66 (Pt 2), pp. 125 - 137

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