TITLE

Genotype-phenotype analysis of the Crohn's disease susceptibility haplotype on chromosome 5q31

AUTHOR(S)
Armuzzi, A.; Ahmad, T.; Ling, K.-L.; de Silva, A.; Cullen, S.; van Heel, D.; Orchard, T.R.; Welsh, K.I.; Marshall, S.E.; Jewell, D.P.
PUB. DATE
August 2003
SOURCE
Gut;Aug2003, Vol. 52 Issue 8, p1133
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background and aims: Recent molecular data suggest that genetic factors may underlie the disease heterogeneity observed in both ulcerative colitis (UC) and Crohn's disease (CD). A locus on chromosome 5q has been implicated in susceptibility to CD, and recently refined by linkage disequilibrium mapping to a conserved 250 kb haplotype (5q31). No data regarding the contribution of this locus to clinical phenotype exist. In this case control study, we investigated the contribution of this haplotype to both susceptibility and phenotype of CD and UC. Patients and methods: We studied 330 Caucasian CD and 457 UC patients recruited from a single UK centre. Association with disease susceptibility and phenotype was analysed with haplotypes reconstructed from three single nucleotide polymorphisms chosen to span this susceptibility region. Evidence for possible genetic epistasis between IBD5 and NOD2/CARD15 was sought. Results: Linkage disequilibrium across this region was confirmed, with two haplotypes comprising 88% of all chromosomes. Susceptibility to CD, but not to UC, was associated with homozygosity for a common haplotype, H2 (p[sub c]=0.002; relative risk (RR) 2.0). Genotype-phenotype analyses demonstrated that this association was particularly strong in patients with perianal disease (p[sub c]=0.0005; RR 1.7), especially in individuals homozygous for this haplotype (p[sub c]=0.0005; RR 3.0). Importantly, no association with H2 was found in 186 patients without perianal disease. No evidence of epistasis between IBD5 and NOD2/CARD15 was demonstrated. Conclusions: The IBD5 risk haplotype is associated with CD only. Genotype-phenotype analysis reveals that the strongest association is observed in patients with perianal CD. While the precise gene involved is unclear, these data provide further molecular evidence for a genetic basis of the clinical heterogeneity of CD.
ACCESSION #
11097191

 

Related Articles

  • Host microbiome signature of Crohn's disease. LaFlamme, Brooke // Nature Genetics;Aug2014, Vol. 46 Issue 8, p811 

    The article discusses the highlights of a study by Lee Denson and colleagues which identified a Crohn's disease-specific gene signature that distinguishes Crohn's disease from ulcerative colitis, published in the July 8, 2014 issue of "The Journal of Clinical Investigation."

  • Differential Effect of Genetic Burden on Disease Phenotypes in Crohn's Disease and Ulcerative Colitis: Analysis of a North American Cohort. Ananthakrishnan, Ashwin N; Huang, Hailiang; Nguyen, Deanna D; Sauk, Jenny; Yajnik, Vijay; Xavier, Ramnik J // American Journal of Gastroenterology;Mar2014, Vol. 109 Issue 3, p395 

    OBJECTIVES:Crohn's disease (CD) and ulcerative colitis (UC) are chronic immunologically mediated diseases with a progressive relapsing remitting course. There is considerable heterogeneity in disease course and accurate prediction of natural history has been challenging. The phenotypic...

  • Association of single nucleotide polymorphisms in the interleukin-4 gene and interleukin-4 receptor gene with Crohn’s disease in a British population. Aithal, G P; Day, C P; Leathart, J; Daly, A K; Hudson, M // Genes & Immunity;Feb2001, Vol. 2 Issue 1, p44 

    Interleukin-4 (IL-4) is an important cytokine in mucosal immunity and plays a critical role in the development of colitis inT-α cell receptor mutant mice. Functionally significant polymorphisms have been described in the genes encoding IL-4 and IL-4 receptor. To examine the role of these...

  • MicroRNA signatures differentiate Crohn's disease from ulcerative colitis. Schaefer, Jeremy S.; Attumi, Taraq; Opekun, Antone R.; Abraham, Bincy; Hou, Jason; Shelby, Harold; Graham, David Y.; Streckfus, Charles; Klein, John R. // BMC Immunology;2015, Vol. 16 Issue 1, p1 

    Background: Excessive and inappropriate immune responses are the hallmark of several autoimmune disorders, including the inflammatory bowel diseases (IBD): Crohn's disease (CD) and ulcerative colitis (UC). A complex etiology involving both environmental and genetic factors influences IBD...

  • Ulcerative colitis and Crohn disease: gene expression profiling using oligonucleotide microarrays. Chakravarti, Shukti; Lawrance, Ian // Nature Genetics;Nov99 Supplement, Vol. 23, p37 

    Presents an abstract for the article on gene expression profiling in ulcerative colitis and Crohn disease using oligonucleotide biochips.

  • Genetics and Ulcerative Colitis: What are the Clinical Implications? Latiano, Anna; Annese, Vito // Current Drug Targets;Sep2011, Vol. 12 Issue 10, p1383 

    Substantial progress has been made in the last years in characterizing the susceptibility genes involved in IBD pathogenesis, especially for Crohn's disease. Although some genetic factors associated with Crohn's disease also predispose individuals to ulcerative colitis, markers specific only for...

  • Influence of polymorphisms and TNF and IL1β serum concentration on the infliximab response in Crohn's disease and ulcerative colitis. Lacruz-Guzmán, Diana; Torres-Moreno, Daniel; Pedrero, Francisco; Romero-Cara, Patricia; García-Tercero, Iván; Trujillo-Santos, Javier; Conesa-Zamora, Pablo // European Journal of Clinical Pharmacology;Mar2013, Vol. 69 Issue 3, p431 

    Aim: Inflammatory bowel diseases (IBD), such as Crohn's disease (CD) and ulcerative colitis (UC), are partially attributable to an increased secretion of proinflamatory cytokines, such as tumour necrosis factor (TNF) and interleukin-1β (IL1β), which play essential roles in the disease...

  • Common variants in the NLRP3 region contribute to Crohn's disease susceptibility. Villani, Alexandra-Chloé; Lemire, Mathieu; Fortin, Geneviève; Louis, Edouard; Silverberg, Mark S.; Collette, Catherine; Baba, Nobuyasu; Libioulle, Cécile; Belaiche, Jacques; Bitton, Alain; Gaudet, Daniel; Cohen, Albert; Langelier, Diane; Fortin, Paul R.; Wither, Joan E.; Sarfati, Marika; Rutgeerts, Paul; Rioux, John D.; Vermeire, Severine; Hudson, Thomas J. // Nature Genetics;Jan2009, Vol. 41 Issue 1, p71 

    We used a candidate gene approach to identify a set of SNPs, located in a predicted regulatory region on chromosome 1q44 downstream of NLRP3 (previously known as CIAS1 and NALP3) that are associated with Crohn's disease. The associations were consistently replicated in four sample sets from...

  • Dysplastic Lesions in Inflammatory Bowel Disease. Matkowskyj, Kristina A.; Chen, Zongming E.; Rao, M. Sambasiva; Yang, Guang-Yu // Archives of Pathology & Laboratory Medicine;Mar2013, Vol. 137 Issue 3, p338 

    Context.-Inflammatory bowel disease (IBD) is a longstanding chronic active inflammatory process in the bowel with increased risk for the development of colorectal carcinoma. Several molecular events involved in chronic active inflammatory processes contribute to multistage progression of human...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sign out of this library

Other Topics