Analysis of the influence of OCTN1/2 variants within the IBD5 locus on disease susceptibility and growth indices in early onset inflammatory bowel disease

Russell, R. K.; Drummond, H. E.; Nimmo, E. R.; Anderson, N. H.; Noble, C. L.; Wilson, D. C.; Gillett, P. M.; McGrogan, P.; Hassan, K.; Weaver, L. T.; Bisset, W. M.; Mahdi, G.; Satsangi, J.
August 2006
Gut;Aug2006, Vol. 55 Issue 8, p1114
Academic Journal
Background and aims: The OCTN1 (SLC22A4 1672C→T) and OCTN2 (SLC22A5 -207G→C) variants within the IBD5 locus have been associated with susceptibility to adult onset Crohn's disease (CD), but their contribution in children has not been examined. Methods: These OCTN1/2 variants and IBD5 marker single nucleotide polymorphisms (SNPs) (IGR2096a•1, IGR2198a•1, and IGR2230a•1) were examined in 299 Scottish children (200 with CD, 74 with ulcerative colitis (UC), and 25 with indeterminate colitis (IC)), together with 502 parents (for transmission disequilibrium testing) and 256 controls. Results: All SNPs were in strong linkage disequilibrium (D' >0.94). TDT analysis showed association of the OCTN1 variant with inflammatory bowel disease (IBD) (p = 0.01) and CD (p = 0.04). Allele frequencies of the OCTN1/2 variants were significantly higher in IBD/CD cases (p<0.04). The homozygous mutant OCTN1/2 haplotype was increased in IBD (24.3% v 16.1%, p=0.02) and UC (28.2% v 16.1%, p=0.02) compared with controls. The OCTN1/2 variants were not independent of the background IBD5 risk haplotype in conferring disease susceptibility. Unifactorial analysis in CD patients showed that carriage of the TC haplotype was associated with lower weight, height, and BMI centile (<9th centile) at diagnosis (weight: 87.9% v 67.3% (p=0.002), odds ratio (OR)= 3.52 (95% confidence interval, 1.51 to 8.22); height: 84.1% v 68.4%(p<0.05), OR=2.44 (1.00 to 5.99); BMI: 79.6% v 61.1% (p=0.02), OR=2.49 (1.14 to 5.44)), and lower weight centile at follow up (87.5% v 64.6% (p=0.03), OR=3.83 (1.03 to 14.24)). Multifactorial binary logistic regression analysis confirmed association of the TC haplotype with lower weight centile at diagnosis (p=0.02, OR= 3.41 (1.20 to 9.66)). Conclusions: These data implicate variants within the IBD5 haplotype, as determinants of disease susceptibility and growth indices in early onset IBD. The OCTN1/2 variants remain potential positional candidate genes, but require further analysis.


Related Articles

  • Tacrolimus Is Safe and Effective in Patients with Severe Steroid-Refractory or Steroid-Dependent Inflammatory Bowel Disease—A Long-Term Follow-Up. Baumgart, Daniel C.; Pintoffl, Jan P.; Sturm, Andreas; Wiedenmann, Bertram; Dignass, Axel U. // American Journal of Gastroenterology;May2006, Vol. 101 Issue 5, p1048 

    OBJECTIVE: We and others have reported the use of tacrolimus in refractory inflammatory bowel disease (IBD). Little is known about its long-term efficacy and safety. METHODS: In this retrospective, observational single center study the charts of 53 adult patients with steroid-dependent (n = 18)...

  • Analysis of IL12B Gene Variants in Inflammatory Bowel Disease. Glas, Jürgen; Seiderer, Julia; Wagner, Johanna; Olszak, Torsten; Fries, Christoph; Tillack, Cornelia; Friedrich, Matthias; Beigel, Florian; Stallhofer, Johannes; Steib, Christian; Wetzke, Martin; Göke, Burkhard; Ochsenkühn, Thomas; Diegelmann, Julia; Czamara, Darina; Brand, Stephan // PLoS ONE;Mar2012, Vol. 7 Issue 3, p1 

    Background:IL12B encodes the p40 subunit of IL-12, which is also part of IL-23. Recent genome-wide association studies identified IL12B and IL23R as susceptibility genes for inflammatory bowel disease (IBD). However, the phenotypic effects and potential gene-gene interactions of IL12B variants...

  • Current Therapy of Inflammatory Bowel Disease in Children. Rufo, Paul A; Bousvaros, Athos // Pediatric Drugs;2006, Vol. 8 Issue 5, p279 

    Ulcerative colitis (UC) and Crohn disease (CD) are chronic intestinal inflammatory diseases that can present as bloody diarrhea, abdominal pain, and malnutrition. Collectively, these disorders are referred to as inflammatory bowel disease (IBD). All patients with IBD share a common...

  • Implications for schools of Inflammatory Bowel Disease. Leigh, Stella // Education Journal;Mar2006, Issue 93, p12 

    The article examines the role of schools in addressing children with Ulcerative Colitis and Crohn's Disease, or what is collectively called Inflammatory Bowel Disease (IBD). Each case of childhood IBD will take its own individual course. Therefore, it is important that the school liaises with...

  • Epidemiological and Psychosocial Aspects of Inflammatory Bowel Disease with Observations on Children, Families, and Pregnancy. Korelitz, B. I. // American Journal of Gastroenterology;Dec1982, Vol. 77 Issue 12, p929 

    The article focuses on epidemiological and psychosocial aspects of inflammatory bowel disease with observations on children, families and pregnancy. Clinical observation substantiated by some objective data suggests that Crohn's disease is more virulent in children than in adults. Ulcerative...

  • Inflammatory Bowel Disease. Noble, Sarah // Pediatrics for Parents;2008, Vol. 24 Issue 1, p2 

    The article offers information on inflammatory bowel disease (IBD) in children. IBD is a chronic autoimmune disease resulting in inflammation of the gastrointestinal tract. Between the two main types of IBD: Crohn's disease and ulcerative colitis, the latter is more prevalent in children....

  • Capsule endoscopy and enteroscopy: modern modalities to investigate the small bowel in paediatrics. Sidhu, R.; Sanders, D. S.; McAlindon, M. E.; Thomson, M. // Archives of Disease in Childhood;Feb2008, Vol. 93 Issue 2, p154 

    Historically the small bowel has been considered a technically difficult area to examine because of its length (3-5 metres), location and tortuosity. Capsule endoscopy and enteroscopy have revolutionised the investigation pathway of the small bowel in adults. They are now developing increasingly...

  • Pediatric Inflammatory Bowel Disease. Antonioli, Donald A. // Pediatric & Developmental Pathology;Jan/Feb2005, Vol. 8 Issue 1, p2 

    Focuses on pediatric inflammatory bowel disease (IBD). Achievement of diagnosis by eliminating known causes of enteritis and colitis; Effects caused by the endoscopic procedure; Effects of colonic cleaning procedures; Histologic features of enteric colitis; Characteristics of pediatric IBD;...

  • Targeting leukocyte migration and adhesion in Crohn's disease and ulcerative colitis. Thomas, Saskia; Baumgart, Daniel // Inflammopharmacology;Feb2012, Vol. 20 Issue 1, p1 

    Crohn's disease and ulcerative colitis are two chronic inflammatory bowel diseases. Current biologic therapies are limited to blocking tumor necrosis factor alpha. However, some patients are primary non-responders, experience a loss of response, intolerance or side effects defining the urgent...


Read the Article


Sign out of this library

Other Topics