Association of MHC class I related gene B (MICB) to celiac disease.
OBJECTIVE
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.


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 (lambdas = 1) and MICA-A5.1 (lambdas = 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%vs 9%, p = 0.0085, pc = NS) and MICB0104 (52%vs 30%, p = 0.01, pc = NS) were increased in DQ2-negative patients. MICA-A5.1 was significantly increased in atypical patients (p(c)= 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 intraepithelial gammadelta and CD8 T cells, together with the data presented here suggest a potential role of MIC genes in the pathogenesis of CD.
González
Segundo
S
Department of Functional Biology, University of Oviedo, Spain.
Rodrigo
Luis
L
López-Vázquez
Antonio
A
Fuentes
Dolores
D
Agudo-Ibáñez
Lorena
L
Rodríguez-Rodero
Sandra
S
Fdez-Morera
Juan Luis
JL
Martínez-Borra
Jesús
J
López-Larrea
Carlos
C
D000328:Adult; D002446:Celiac Disease / Q000235:genetics*; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008297:Male
D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A; C098080:MICB antigen