MHC class I chain-related gene B (MICB) is associated with rheumatoid arthritis susceptibility.
OBJECTIVE
Several recent studies have shown that the MHC class III region, located telomeric to HLA-DRB1, contains an additional genetic factor that predisposes to rheumatoid arthritis (RA). In this study, we investigate whether inhibitor of kappaB-like (IkappaBL), MICB or MICA located in the MHC class III region are the second susceptibility gene associated with RA.


METHODS
A total of 154 healthy controls and 140 RA patients were genotyped for HLA-DRB1, MICA, MICB and the polymorphism -62 of the IkappaBL gene.


RESULTS
A significant increase of HLA-DRB1 shared epitope (SE) alleles was detected in RA patients (61.4 vs 43.5%, P(c) = 0.01, OR = 2.1, 95% CI = 1.3-3.3). Among SE alleles, the HLA-DRB1*0401 (13.5 vs 5.1%, P(c) = 0.04, OR = 3.2, 95% CI = 1.3-8.1) and HLA-DRB1*0404 (6.4 vs 1.2%, P = 0.02, P(c) = NS) showed the most significantly association with RA. No increase of risk was associated with HLA-DRB1*01. Remarkably, the allele MICB*004 was also significantly associated with RA susceptibility (40.7 vs 23.3%, P(c) = 0.01, OR = 2.2, 95% CI = 1.3-3.7). MICB*004 was in linkage disequilibrium with HLA-DRB1*0404 (lambda(s) = 0.33) and HLA-DRB1*0405 (lambda(s) = 0.34). However, MICB*004 was also increased in HLA-DRB1 SE negative patients (37 vs 21.5%, P = 0.04). No significant association between IkappaBL and MICA with RA was found.


CONCLUSIONS
MICB*004 allele was associated with RA susceptibility. This allele was in linkage disequilibrium with HLA-DRB1*0404 and DRB1*0405. The association of MICB with RA susceptibility and the functional role of MIC genes in the pathogenesis of RA converts MICB into a candidate to be an additional MHC gene associated with RA susceptibility.
López-Arbesu
R
R
Department of Functional Biology, Universidad de Oviedo, Oviedo, Spain.
Ballina-García
F J
FJ
Alperi-López
M
M
López-Soto
A
A
Rodríguez-Rodero
S
S
Martínez-Borra
J
J
López-Vázquez
A
A
Fernández-Morera
J L
JL
Riestra-Noriega
J L
JL
Queiro-Silva
R
R
Quiñones-Lombraña
A
A
López-Larrea
C
C
González
S
S
D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006650:Histocompatibility Testing / Q000379:methods; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged
D048868:Adaptor Proteins, Signal Transducing; C488436:HLA DRB1*04:04 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553505:HLA-DRB1*04:01 antigen; C493960:HLA-DRB1*04:05 antigen; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; C098080:MICB antigen; C120111:NFKBIL1 protein, human