The contribution of human leucocyte antigen complex genes to disease phenotype in ulcerative colitis

Ahmad, Tariq; Armuzzi, Alessandro; Neville, Matt J.; Bunce, Mike; Ling, Khoon‐Lin; Welsh, Ken I.; Marshall, Sara E.; Jewell, D P

doi:10.1046/j.1399-0039.2003.00129.x

Cited by 86 publications

(65 citation statements)

References 76 publications

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“…Earlier studies of the HLA class II genes in UC have focused on phenotypic and not allelic associations. 12,18 However, even the frequency of the DRB1*0401 phenotype was similar in patients with UC as compared with healthy controls (23.0 versus 23.4%, P ¼ 0.90), whereas decreased among patients with PSC (9.6 versus 23.4%, P ¼ 10 À6 ). The only significant HLA class II association detected in our Scandinavian UC population, was a previously unreported decrease in the frequency of the DRB1*0404 allele in the patients as compared with the healthy controls ( Table 4, P corrected ¼ 0.03; Bonferroni correction factor of 32 according to the number of DRB1 alleles).…”

Section: Resultsmentioning

confidence: 92%

“…In particular, no overall effects of DRB1*04 alleles on UC susceptibility was evident (OR ¼ 0.82, 95% CI (0.63, 1.1), P ¼ 0.14), whereas these alleles conferred strong protection against PSC (OR ¼ 0.28, 95% CI (0.20, 0.39), P ¼ 10 À13 ). Furthermore, the frequency of the DRB1*0401 allele, specifically reported to confer protection against UC, 18 was almost identical in UC patients as compared with healthy controls whereas decreased among patients with PSC (Table 4). Earlier studies of the HLA class II genes in UC have focused on phenotypic and not allelic associations.…”

Section: Resultsmentioning

confidence: 97%

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Different HLA class II associations in ulcerative colitis patients with and without primary sclerosing cholangitis

et al. 2007

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Approximately 80% of patients with primary sclerosing cholangitis (PSC) of Northern European origin have inflammatory bowel disease (IBD), the majority ulcerative colitis (UC). An inherent problem in interpreting positive findings in genetic association studies of PSC is thus to distinguish between factors associated with hepatobiliary versus intestinal pathology. We aimed to clarify to what extent human leukocyte antigen (HLA) class II associations in UC patients with and without PSC differ. Highresolution DRB1 and DQB1 typing was performed in 365 Scandinavian PSC patients, an independent cohort of 330 Norwegian UC patients and 368 healthy controls. HLA associations found in PSC were mostly distinct from those seen in UC, and no significant differences were noted between PSC patients with concurrent UC and PSC patients without IBD. This suggests different HLA associated genetic susceptibility to PSC and UC, and supports notions that UC in PSC may represent a distinct UC phenotype.

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Section: Resultsmentioning

confidence: 92%

Section: Resultsmentioning

confidence: 97%

Different HLA class II associations in ulcerative colitis patients with and without primary sclerosing cholangitis

et al. 2007

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“…The most consistently reproducible finding is HLA-DRB1*0701 [170][171][172][173] Ulcerative colitis HLA-DRB1*0103 and *1502 HLA-DRB1*0103 is the most reproducible association 170,174,175 Graves disease HLA-DRB1*03-DQB1*02-DQA1*0501 Logistic-regression analysis shows that the association could be explained by either DRB1 or DQA1 176,177 Hashimoto 0 s thyroiditis HLA-DRB1*04-DQB1*03-DQA1*03…”

Section: Regulation Of Mhc Class II Gene Expressionmentioning

confidence: 99%

Regulation of major histocompatibility complex class II gene expression, genetic variation and disease

et al. 2009

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Major histocompatibility complex (MHC) class II molecules are central to adaptive immune responses and maintenance of selftolerance. Since the early 1970s, the MHC class II region at chromosome 6p21 has been shown to be associated with a remarkable number of autoimmune, inflammatory and infectious diseases. Given that a full explanation for most MHC class II disease associations has not been reached through analysis of structural variation alone, in this review we examine the role of genetic variation in modulating gene expression. We describe the intricate architecture of the MHC class II regulatory system, indicating how its unique characteristics may relate to observed associations with disease. There is evidence that haplotypespecific variation involving proximal promoter sequences can alter the level of gene expression, potentially modifying the emergence and expression of key phenotypic traits. Although much emphasis has been placed on cis-regulatory elements, we also examine the role of more distant enhancer elements together with the evidence of dynamic inter-and intra-chromosomal interactions and epigenetic processes. The role of genetic variation in such mechanisms may hold profound implications for susceptibility to common disease.

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“…NOD2, the first gene linked with increased susceptibility to CD, has later been shown to be associated with ileal disease, early age of onset, stricturing, and/or penetrating phenotype and increased need for surgery [5,9,10,[38][39][40][41][42][43][44][45][46][47][48][49]. Among the UC susceptibility genes, HLA DRB1*0103 and the multidrug resistance gene 1 (MDR1/ABCB1) were also identified as being associated with extensive and severe disease [17,[23][24][25][26][27][28][29][30][31][32][33][34][35][36][37].…”

Section: Discussionmentioning

confidence: 99%

“…Among the UC susceptibility genes, HLA DRB1*0103 and the multidrug resistance gene 1 (MDR1/ABCB1) also contribute to clinical phenotype and natural history, being associated with extensive and severe disease [17,[23][24][25][26][27][28][29][30][31][32][33][34][35][36][37]. In CD, NOD2 gene mutations have repeatedly been shown to be associated with ileal disease, early age of onset, stricturing, and/or penetrating phenotype and increased need for surgery [5,9,10,[38][39][40][41][42][43][44][45][46][47][48][49].…”

Section: Introductionmentioning

confidence: 99%

NOD2 gene mutations in ulcerative colitis: useless or misunderstood?

Freire

Cardoso

Figueiredo

et al. 2014

Int J Colorectal Dis

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Purpose NOD2 mutations have been linked to an increased risk of Crohn's disease and to some of its phenotypes. The association between NOD2 mutations and susceptibility to ulcerative colitis (UC) remains somewhat controversial and potential correlations between these mutations and UC phenotype have not been studied. Aim To assess whether NOD2 mutations are a risk factor for UC in Portugal and if there are any genotype-phenotype correlations in these patients. Methods The three main NOD2 mutations were searched in 200 patients with UC and in 202 healthy controls. Results NOD2 mutations were present in 28 patients with UC (14.0 %) and in 27 controls (13.4 %) (p=0.853). Mutation carriers were more likely to receive steroids during the first year of disease than non-carriers (54.2 % vs. 29.6 %, p= 0.018) and among these patients the need for intravenous administration was more frequent in those with the R702W polymorphism (90.0 % vs. 45.5 %, p=0.014). In patients with severe colitis admitted for intravenous steroids, a greater proportion of mutation carriers was considered intravenous-steroid refractory and required salvage therapy (90.0 % vs. 38.1 %, p=0.004). Patients with NOD2 mutation were submitted to colectomy more frequently than non-carriers (17.9 % vs. 4.1 %. p=0.015). No correlation with the need for immunosuppressants/immunomodulators was found. Conclusions In the Portuguese population, NOD2 mutations do not increase the risk of UC but are associated with a more aggressive course including greater need of steroids in the first

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The contribution of human leucocyte antigen complex genes to disease phenotype in ulcerative colitis

Cited by 86 publications

References 76 publications

Different HLA class II associations in ulcerative colitis patients with and without primary sclerosing cholangitis

Different HLA class II associations in ulcerative colitis patients with and without primary sclerosing cholangitis

Regulation of major histocompatibility complex class II gene expression, genetic variation and disease

NOD2 gene mutations in ulcerative colitis: useless or misunderstood?

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