Analysis of the CTLA4 gene in Swedish coeliac disease patients

Background: A genetic susceptibility to coeliac disease is well established. involving HLA and non-HLA components. CTLA4 is an important regulator of T-cell function and some studies have suggested that sequence variation in the gene might be a determinant of disease susceptibility, although the evidence is conflicting. Methods: Sixty-two children with biopsy-proven coeliac disease attending a single centre in Sweden were studied. All were genotyped for presence of the HLA-DQA1*0501, B1*0201 alleles. Those who carried the HLA-DQ heterodimer (58/62) were genotyped for the +49 (A/G) exon I polymorphism. The transmission disequilibrium test (TDT) was used to test for association between coeliac disease and the A allele. The entire CTLA4 gene was screened for other sequence variants using a combination of conformation-sensitive gel electrophoresis and direct sequencing. Results: A significant association between the exon I polymorphism and coeliac disease was observed (P = 0.02). No other sequence variants in CTLA4 were detected, Conclusions: This study provides further evidence that variation in CTLA4 is a determinant of coeliac disease susceptibility. If not mediated through the +49 (A/G) dimorphism directly, then the effect is likely to be mediated through linkage disequilibrium.