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E.H. Hughes, R.W. M. Collins, E. Kondeatis, G.R. Wallace, E.M. Graham, R.W. Vaughan, M.R. Stanford; Associations of MHC Class I Chain–Related Molecule (MIC) Polymorphisms With Behcet’s Disease in Caucasian Patients . Invest. Ophthalmol. Vis. Sci. 2005;46(13):5107.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To investigate MHC class I chain–related molecule (MIC) associations in a group of western European Caucasian patients with Behcet’s disease (BD). The HLA–B*51 allele is known to be associated with BD in many ethnic groups. The pathogenic gene however may lie close to the HLA–B locus and therefore be in linkage disequilibrium with HLA–B*51. On the basis of the proximity of MIC genes to HLA–B, their expression pattern, and their affinity for the activating NKG2D receptor on natural killer cells and γΔ T cells, these molecules have been postulated as susceptibility factors in BD. Methods: DNA from 56 western European Caucasians with BD and 90 Caucasian controls were analysed by polymerase chain reaction using allele–specific primers for MICA and MICB alleles. 43 (77%) of the patients had ocular involvement. Results:An increased allele frequency of MICA*009 was found in the BD patient group (25.0%) when compared with controls (7.2%) (Χ2 17.2, p<0.0001). This was associated with a corresponding decrease in MICA*008 in the BD patients (36.6%) compared with controls (46.7%), which was not significant. MICA*009 was strongly associated with the presence of HLA–B*51 in patients (Χ2 48.23, p< 0.0001) and controls (Χ2 38.4, p<0.0001). No significant difference in frequency of MICB alleles was found between patients and controls. Conclusions: Both HLA–B*51 and MICA*009 are strongly associated with BD and the two alleles are in linkage disequilibrium. MICA associations with HLA–B51 and BD have been found in studies on Middle Eastern and Korean BD patients but have never been previously examined in a pure Caucasian BD patient group. This is the first study of MICB allelic polymorphism in patients with BD and no MICB allele was found to significantly associate with the disease; an unexpected finding considering the close proximity of the MICA and MICB loci on chromosome 6. Our results suggest that whilst MICB appears not to influence the development of the BD, polymorphisms in MICA may be pathogenic, perhaps through interaction with natural killer and γΔ T cells.
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