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

In English

Författare

  • S Popat
  • N Hearle
  • L Hogberg
  • CP Braegger
  • D O'Donoghue
  • K Falth-Magnusson
  • GKT Holmes
  • PD Howdle
  • H Jenkins
  • S Johnston
  • NP Kennedy
  • PJ Kumar
  • RFA Logan
  • MN Marsh
  • CJ Mulder
  • AT Naluai
  • Klas Sjöberg
  • L Stenhammar
  • JRF Walters
  • DP Jewell
  • RS Houlston
Visa allt

Summary, in English

Susceptibility to coeliae 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 coeliae 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 (910 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.

Avdelning/ar

Publiceringsår

2002

Språk

Engelska

Sidor

125-137

Publikation/Tidskrift/Serie

Annals of Human Genetics

Volym

66

Issue

2

Dokumenttyp

Artikel i tidskrift

Förlag

Wiley-Blackwell

Ämne

  • Clinical Medicine

Status

Published

Forskningsgrupp

  • Chronic Inflammatory and Degenerative Diseases Research Unit
  • Gastroenterology

ISBN/ISSN/Övrigt

  • ISSN: 1469-1809