Association of HLA class II genes with susceptibility to Crohn's disease.

Danzé, Pierre‐Marie; Jf, Colombel; Jacquot, Serge; Loste, M N; Héresbach, D.; Ategbo, S; Khamassi, S; Périchon, Bruno; Sémana, G.; Charron, Dominique; Cézard, Jean-Pierre

doi:10.1136/gut.39.1.69

Cited by 76 publications

(37 citation statements)

References 23 publications

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“…We had previously noted the DR1-DQ5 association in Jewish and non-Jewish Caucasian CD patients [12,26]. Several other groups have identified a DR1 association to IBD/CD in Caucasians in the United States [15], France [25], and the Netherlands [9]. The recent study of Satsangi et al from Japan using DNA typing also indicates a significant association with the DRB1*0103 allele and UC in the Japanese population [14].…”

Section: Discussionmentioning

confidence: 74%

“…However, three studies in Japanese populations using DNA typing methods indicated that DRB1*1501 showed a protective association with CD [23], and DRB1*1502 showed an association with UC [16,24]. In other serologic studies, the HLA class II DR1-DQ5 haplotype was found to be associated with CD in Caucasians [12,15,25]. Moreover, recent molecular analyses of the HLA class II genes in Japanese [16,23,24] and Caucasian populations [13,[26][27][28] (including the current study) demonstrated significant HLA class II allele and haplotype associations with IBD.…”

Section: Introductionmentioning

confidence: 97%

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HLA class II haplotype associations with inflammatory bowel disease in Jewish (Ashkenazi) and non-Jewish Caucasian populations

Trachtenberg¹,

Yang

Hayes³

et al. 2000

Human Immunology

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Ulcerative colitis (UC) and Crohn's disease (CD) are the clinical entities comprising idiopathic inflammatory bowel disease (IBD). Previous studies on the association of IBD and human leukocyte antigen (HLA) class II genes suggested a role for HLA in this disease. Here we present HLA class II (DRB1, DQB1, DQA1, DPB1) allele and haplotype distributions determined using the polymerase chain reaction and sequence-specific oligonucleotide probe methods. A total of 578 UC and CD Caucasian patients and controls from Jewish (Ashkenazi) and non-Jewish populations was examined. Our previously reported association of DR1-DQ5 with CD was attributable to DRB1*0103. A dramatic association with IBD and the highly unusual DRB1*0103-DQA1*0501-DQB1*0301 haplotype (OR = 6.6, p = 0.036) was found. The more common DR1 haplotype, DRB1*0103-DQA1*0101-DQB1*0501, was also associated with IBD (OR = 3.1, p = 0.014), a result suggesting that interaction between DR and DQ may determine the extent of disease risk. Our previously reported association of DR2 with UC was attributable to DRB1*1502 (OR = 2.6, p = 0.006). At the DPB1 locus, a significant association of DPB1*0401 with CD was observed for the combined populations (OR = 1.85, p = 0.007). These observations indicate that some class II alleles and haplotypes confer susceptibility to both UC and CD, implying common immunogenetic mechanisms of pathogenesis, while others confer risk to only one of these diseases, and illustrate the value of DNA HLA typing in disease susceptibility analyses.

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Section: Discussionmentioning

confidence: 74%

Section: Introductionmentioning

confidence: 97%

HLA class II haplotype associations with inflammatory bowel disease in Jewish (Ashkenazi) and non-Jewish Caucasian populations

Trachtenberg¹,

Yang

Hayes³

et al. 2000

Human Immunology

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“…In contrast with other immune-mediated complex diseases such as rheumatoid arthritis, multiple sclerosis and IDDM, results on the role of the MHC complex in IBD are inconsistent, heterogeneous and often very weak. [64][65][66][67] In Japanese studies, HLA DR2 (HLA DRB1*1502) has been implicated in UC, whereas HLA DR3 (HLA DRB1*0103) has been implicated in European studies. In CD, HLA associations are less convincing.…”

Section: Current Status Of Genetics Research In Ibd S Vermeire and P mentioning

confidence: 99%

Current status of genetics research in inflammatory bowel disease

Vermeire¹,

Rutgeerts²

2005

Genes Immun

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The research on genetic susceptibility of inflammatory bowel diseases (IBD) has been tremendous and over 10 chromosomal regions have been identified by genome-wide scanning. Further fine mapping as well as candidate gene studies have already led to the identification of a number of susceptibility genes including CARD15, DLG5, OCTN1 and 2, NOD1, HLA, and TLR4. The CARD15 gene is undoubtedly replicated most widely and most understood at present. CARD15 is involved in the recognition of bacterial peptidoglycan-derived muramyl dipeptide (MDP) and will stimulate secretion of antimicrobial peptides including alpha-defensins (also called cryptdins) to protect the host from invasion. Genetic research in IBD has advanced our understanding of the clinical heterogeneity of the disease and has started to tackle the complex interactions between genetic risk factors and environmental risk factors in IBD. Genes also interfere with the metabolization of drugs and may influence the clinical response and the drug-related toxicity. Interesting pharmacogenetic data with respect to steroids, azathioprine, and infliximab have been generated in IBD. Overall, it is anticipated that genetic markers in the future will be implemented in an integrated molecular diagnostic and prognostic approach of our patients. Genes and Immunity (2005) 6, 637-645.

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“…was the study by Yang et al [77] [21,39,41,53,55,83,84]. In CD, we found no [89] showed that in 4 patients who demonstrated clinical and endoscopic improvement with cA2 infusion there was association between disease in general and any HLA allele tested.…”

Section: Hla and Cytokine Gene Polymorphisms In Well-characterized Sumentioning

confidence: 70%

“…Two studies from Europe had previously observed a decreased served. Studies correlating genetic polymorphisms of these cytokines with clinical response may provide imporfrequency of HLA-DR3 in their unselected CD patients [84,86]. In these studies, no data on clinical features tant clues to understand the effectiveness of humanized monoclonal antibodies in these diseases were provided.…”

Section: Hla and Cytokine Gene Polymorphisms In Well-characterized Sumentioning

confidence: 99%

Genetics of Inflammatory Bowel Disease. The Candidate Gene Approach: Susceptibility versus Disease Heterogeneity

Peña

1998

Dig Dis

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Ulcerative colitis and Crohn’s disease are complex diseases of unknown etiology. Several genes are involved in the susceptibility. These genes are necessary to suffer from these diseases but not sufficient. Environmental factors trigger the inflammatory response. Evidence is accumulating that this response is abnormal in these patients. Therefore, the study of genes that are involved in the regulation of the inflammation may help to clarify the pathogenesis of the disease. The working hypothesis is that HLA and cytokine gene polymorphisms, of extreme importance in the regulation of inflammation, contribute to determining the heterogeneity of the disease and the prognosis. In this case, the candidate genes are those involved in the regulation of the immune response of the host. These studies may be of great importance in the tailoring of an appropriate treatment for particular subgroups of patients. A premise for the success of these studies is to use a solid classification, which should take into account the dynamic process and the natural evolution of the disease; to use a carefully selected and ethnically matched group of healthy controls, and to use the advanced molecular biological typing techniques. In the present article, this concept is explored by taking into account some of the recent findings obtained with the HLA and cytokine gene polymorphisms in inflammatory bowel diseases. The results support the concept that these gene polymorphisms are of greater importance in determining the severity of the disease than in determining the susceptibility to suffer from the disease. From this point of view, these studies are complementary and a necessary addition to studies using the whole genome approach in the effort to understand the genetics of these chronic multifactorial diseases.

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Association of HLA class II genes with susceptibility to Crohn's disease.

Cited by 76 publications

References 23 publications

HLA class II haplotype associations with inflammatory bowel disease in Jewish (Ashkenazi) and non-Jewish Caucasian populations

HLA class II haplotype associations with inflammatory bowel disease in Jewish (Ashkenazi) and non-Jewish Caucasian populations

Current status of genetics research in inflammatory bowel disease

Genetics of Inflammatory Bowel Disease. The Candidate Gene Approach: Susceptibility versus Disease Heterogeneity

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