DLG5 variants do not influence susceptibility to inflammatory bowel disease in the Scottish population

Noble, C. L.; Nimmo, E. R.; Drummond, H.; Smith, L.; Arnott, I. D. R.; Satsangi, J.
October 2005
Gut;Oct2005, Vol. 54 Issue 10, p1416
Academic Journal
Introduction: Recent data have suggested that specific haplotypic variants of the DLG5 gene on chromosome 10q23 may be associated with susceptibility to inflammatory bowel disease (IBD) in Germany. Haplotype D, notably characterised by the presence of a G→A substitution at nucleotide 113, was associated with susceptibility to Crohn's disease (CD) whereas an extended haplotype A conferred protection. Aims: Association of DLG5 haplotypic variants with disease susceptibility, genotype-phenotype relationships, and epistasis with CARD 15 was investigated in the Scottish population. Patients and methods: A total of 374 CD, 305 ulcerative colitis (UC), and 294 healthy controls (HC) were studied. Genotyping for the variants rs1248696 (113A, representing haplotype D) and the single nucleotide polymorphism tag rs2289311 (representing haplotype A) were typed using the Taqman system. Results: On analysis of the DLG5 variant 113A, there were no associations with IBD when allelic frequency (11.4% IBD v 13.2% HC; p=0.30) and carrier frequency (19.2% IBD v 24.6% HC; p =0.069) were analysed. No associations were observed between 11 3A variant allelic frequency (p=0.37), carrier frequency (p =0.057), and CD. In fact, 113A heterozygosity rates were lower in CD (16%) and IBD (16.9%) than in HC (23%) (p =0.029 and p = 0.033, respectively). No associations between DIGS and UC were observed. Haplotype A was not protective and there was no evidence of epistasis between DLG5 and CARD15. Conclusions: The present data contrast strongly with previous data from Germany. DLG5 113A is not associated with disease susceptibility and haplotype A does not confer resistance. Further work is required to evaluate the significance of DLG5 in other populations from geographically diverse regions.


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