The 14-bp deletion polymorphism in the HLA-G gene displays significant differences between ulcerative colitis and Crohn's disease and is associated with ileocecal resection in Crohn's disease

Glas, Jürgen; Török, Helga-Paula; Tonenchi, Laurian; Wetzke, Martin; Beynon, Vanessa; Teshome, Molla Y; Cotofana, Sebastian; Schiemann, Uwe; Griga, Thomas; Klein, Wolfram; Epplen, Joerg T; Folwaczny, Christian; Folwaczny, Matthias; Mussack, Thomas; Weiss, Elisabeth H (2007). The 14-bp deletion polymorphism in the HLA-G gene displays significant differences between ulcerative colitis and Crohn's disease and is associated with ileocecal resection in Crohn's disease. International immunology, 19(5), pp. 621-6. Oxford: Oxford University Press 10.1093/intimm/dxm027

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HLA-G is a non-classical MHC class Ib molecule predominantly expressed in cytotrophoblasts and under pathological conditions also in chronically inflamed and in malignant tissues. Recently an increased expression of HLA-G was found in ulcerative colitis (UC), but not in Crohn's disease (CD). The HLA-G gene is located in IBD3, a linkage region for inflammatory bowel disease (IBD). A 14-bp deletion polymorphism (Del+/Del-) within exon 8 of the HLA-G gene might influence transcription activity and is therefore of potential functional relevance. To investigate whether the 14-bp deletion polymorphism is associated with IBD, 371 patients with CD, 257 patients with UC and 739 controls were genotyped. The heterozygous genotype (P = 0.031) and the Del+ phenotype (P = 0.038) were significantly increased, whereas the homozygous Del- phenotype (P = 0.038) was significantly decreased in UC when compared with CD. Thus, the 14-bp deletion polymorphism within the HLA-G gene displayed significant differences between UC and CD. Moreover, a significant increase of the Del+ allele (P = 0.002) and the Del+/Del+ genotype (P = 0.013) and a consecutive decrease of the Del-/- genotype (P = 0.024) were observed in those CD cases positive for ileocecal resection. Thus, a potential effect of the HLA-G gene in IBD may affect both UC and CD. Other polymorphisms linked to the 14-bp deletion polymorphism might also contribute to immunopathogenesis. As there are several partly functional polymorphisms within the promoter region potentially influencing HLA-G expression, further studies in IBD are necessary in the context of differential expression of HLA-G between UC and CD.

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