TITLE

Association of MHC Class I Related Gene B (MICB) to Celiac Disease

AUTHOR(S)
González, Segundo; Rodrigo, Luis; López-Vázquez, Antonio; Fuentes, Dolores; Agudo-Ibáñez, Lorena; Rodríguez-Rodero, Sandra; Fdez-Morera, Juan Luis; Martínez-Borra, Jesús; López-Larrea, Carlos
PUB. DATE
April 2004
SOURCE
American Journal of Gastroenterology;Apr2004, Vol. 99 Issue 4, p676
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
BACKGROUND AND AIMS: Celiac disease (CD) is an enteropathic disorder characterized by strong association with HLA-DQ2. Our aim was to investigate whether MICB, a gene located in the MHC class I region, may contribute to CD susceptibility.PATIENTS AND METHODS: Total of 133 CD patients, previously reported to be associated with MICA-A5.1, and 116 controls were initially analyzed. Twenty-eight additional DQ2-negative CD patients were also studied. MICB was typed by PCR using sequence-specific primers. HLA-B, -DRB1, -DQA1, -DQB1, and MICA were also typed.RESULTS: The allele MICB0106 was strongly associated with CD (pc<0.000001, odds ratio (OR)= 5.6, 95% confidence interval (CI)= 3.1–10.1) and it was overrepresented in atypical patients compared with typical ones (pc= 0.04, OR= 2.9, CI= 1.4–6.1). MICB0106 was part of DR3-DQ2 haplotype (B8-MICA-A5.1-MICB0106-DR3-DQ2), and consequently a strong linkage disequilibrium between MICB0106 with DQ2 (λs= 1) and MICA-A5.1 (λs= 0.55) was found. To analyze whether the association of MICB is independent of this haplotype, its association was also studied in DQ2-negative patients (n= 46). DQ8 (28%vs9%, p= 0.0085,pc= NS) and MICB0104 (52%vs30%, p= 0.01,pc= NS) were increased in DQ2-negative patients. MICA-A5.1 was significantly increased in atypical patients (pc= 0.001, OR= 6.4, CI= 2.2–18.4), and this association was independent of DQ2 and DQ8 (pc= 0.02, OR= 2.6, CI= 1.1–6.1).CONCLUSIONS: The expression of MIC genes on enterocytes under stressful conditions and their function as ligands of intraepithelialγδ and CD8 T cells, together with the data presented here suggest a potential role of MIC genes in the pathogenesis of CD.
ACCESSION #
14816819

 

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