Genetics in coeliac disease.
Coeliac disease has a strong genetic component, higher than for many other common complex diseases. Possession of the HLA-DQ2 variant is required for presentation of disease causing dietary antigens to T cells, although this is also common in the healthy population. Non-HLA genetic factors account for the majority of heritable risk. Linkage studies have identified promising regions on chromosomes 5 and 19, with multiple other loci awaiting definitive confirmation in independent studies. Inherited variants in the tightly clustered chromosome 2q CD28-CTLA4-ICOS region are associated with disease, although of weak effect size. Larger sample sizes are necessary in coeliac disease genetic studies to detect small effects, alternatively meta-analysis offers promise. Newer methods including gene expression analysis and genome wide association studies will advance understanding of genetic susceptibility. Identification of coeliac disease genes may improve diagnostic/prognostic markers, basic understanding of disease aetiology, permit development of novel therapeutics and provide insight into other autoimmune disorders.
van Heel
David A
DA
Department of Gastroenterology, Imperial College London, Du Cane Road, London W12 0NN, UK. d.vanheel@imperial.ac.uk
Hunt
Karen
K
Greco
Luigi
L
Wijmenga
Cisca
C
D002446:Celiac Disease / Q000235:genetics*; D002986:Clinical Trials as Topic; D020022:Genetic Predisposition to Disease; D006801:Humans