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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.

Original publication

DOI

10.1017/S0003480002001021

Type

Journal article

Journal

Ann Hum Genet

Publication Date

03/2002

Volume

66

Pages

125 - 137

Keywords

Abatacept, Adolescent, Adult, Aged, Antigens, CD, Antigens, Differentiation, CD28 Antigens, CTLA-4 Antigen, Celiac Disease, Child, Child, Preschool, Chromosomes, Human, Pair 2, Europe, Female, Genetic Linkage, Genetic Markers, Genetic Predisposition to Disease, Genotype, Humans, Immunoconjugates, Infant, Male, Middle Aged, Risk, Statistics, Nonparametric, T-Lymphocytes