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

Colin L Noble ¹, Elaine R Nimmo ¹, Hazel Drummond ¹, Linda Smith ¹, Ian D Arnott ¹ and Jack Satsangi ^1*

¹ University of Edinburgh, United Kingdom

^* To whom correspondence should be addressed. E-mail: j.satsangi{at}ed.ac.uk.

Accepted 11 April 2005

Abstract

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 to 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 CARD15 was investigated in the Scottish population.

Patients and methods: 374 CD, 305 ulcerative colitis (UC) and 294 healthy controls (HC) were studied. Genotyping for the variants rs1248696 (113A, representing haplotype D) and the SNP 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 analyzed. No associations were observed between 113A 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 HC (23%) (P=0.029 and P=0.033 respectively). No associations between DLG5 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.

Keywords: Crohn's disease, DLG5, genetic susceptibility, inflammatory bowel disease, ulcerative colitis

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Relevant Articles

DLG5 variants and susceptibility to inflammatory bowel disease in the Scottish population • Authors’ reply

B L Browning, J Satsangi, C Noble, I D R Arnott, R K Russell, and E R Nimmo
Gut 2006 55: 1050. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

• Van Limbergen, J, Russell, R K, Nimmo, E R, Drummond, H E, G, D., Wilson, D C, Satsangi, J (2009). Germline variants of IRGM in childhood-onset Crohn's disease. Gut 58: 610-611 [Full Text]  
• Browning, B L, Annese, V, Barclay, M L, Bingham, S A, Brand, S, Buning, C, Castro, M, Cucchiara, S, Dallapiccola, B, Drummond, H, Ferguson, L R, Ferraris, A, Fisher, S A, Gearry, R B, Glas, J, Henckaerts, L, Huebner, C, Knafelz, D, Lakatos, L, Lakatos, P L, Latiano, A, Liu, X, Mathew, C, Muller-Myhsok, B, Newman, W G, Nimmo, E R, Noble, C L, Palmieri, O, Parkes, M, Petermann, I, Rutgeerts, P, Satsangi, J, Shelling, A N, Siminovitch, K A, Torok, H-P, Tremelling, M, Vermeire, S, Valvano, M R, Witt, H (2008). Gender-stratified analysis of DLG5 R30Q in 4707 patients with Crohn disease and 4973 controls from 12 Caucasian cohorts. J. Med. Genet. 45: 36-42 [Abstract] [Full Text]  
• Trinh, T T, Rioux, J D (2005). The promise and perils of interpreting genetic associations in Crohn's disease. Gut 54: 1354-1357 [Full Text]