Association of the MIC-A gene and HLA-B51 with Behçet's disease in Arabs and non-Ashkenazi Jews in Israel. Issue 2 (1st February 2002)

• Record Type: Journal Article
• Authors: Cohen, R; Metzger, S; Nahir, M; Chajek-Shaul, T
• Is Part Of: Annals of the rheumatic diseases. Volume 61:Issue 2(2002)
• Page Start: 157
• Page End: 160
• Publication Date: 2002-02-01
• Subjects: Behçet's disease -- HLA-B51 -- MIC-A gene; BD, Behçet's disease -- MIC-A, major histocompatibility complex class I related gene A -- NAJ, non-Ashkenazi Jews -- PCR, polymerase chain reaction -- TM, transmembrane; Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/ard.61.2.157
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: Behçet's disease is known to be strongly associated with HLA-B51 in many different ethnic groups. Recently, it was suggested that MIC-A (major histocompatibility complex class I related gene A) is the pathogenic gene after strong association was found between the MIC-A A6 allele of the transmembrane region and the disease in Japanese and Greek patients, although in Greek patients this association was found to be due to linkage disequilibrium with HLA-B51. Objectives: To investigate microsatellite polymorphism in Arab and non-Ashkenazi Jewish (NAJ) patients in Israel, to determine whether this association occurs in these groups with Behçet's disease, and elucidate the associated HLA allele of the disease. Methods: Forty four Israeli patients with Behçet's disease, including 20 Arabs and 24 NAJ, and 130 ethnically matched healthy controls were examined for MIC-A microsatellite polymorphism of the transmembrane region using polymerase chain reaction, autoradiography, and sequence analysis. Results: The MIC-A A6 allele was significantly more frequent in the Arab patient group (19/20 (95%)) than in healthy Arab controls (25/42 (60%)) (pcorr =0.015, OR=12.92), but not in the NAJ patients (16/24 (67%)) compared with NAJ healthy controls (48 /88 (55%)) (pcorr =1.02, OR=1.667). In stratification analysis of the Arab subgroup, on the confounding effect of MIC-A A6 on HLA-B51 association and vice versa, Behçet's disease was distinctly associated only with HLA-B51. Conclusions: These results imply strong association between the MIC-A A6 allele and the disease in Israeli Arabs, but not in Israeli NAJ patients. The stratification analysis indicates that this association results secondarily from a strong linkage disequilibrium with HLA-B51, and the real disease susceptibility gene which plays a part in the development of Behçet's disease is most probably the HLA-B51 allele itself.