HLA‐B*51 allele analysis by the PCR‐SBT method and a strong association of HLA‐B*5101 with Japanese patients with Behçet’s disease

Mizuki, Nobuhisa; Ôta, Masao; Katsuyama, Yoshihiko; Yabuki, Kazuro; Ando, Hitoshi; Shiina, Takashi; Nomura, Eiichi; Onari, Katsuhiro; Ohno, Shigeaki; Inoko, Hidetoshi

doi:10.1034/j.1399-0039.2001.580306.x

Cited by 55 publications

(43 citation statements)

References 13 publications

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“…Mizuki et al suggested that a genetic predisposition to BD appears to play an important role with a strong association with the MICA gene rather than HLA B51 (6), but a recent report has suggested that the real pathogenic gene for BD is the HLA-B gene itself and the HLA-B * 51 allele is the major susceptibility gene responsible for the development of BD (4,13,15,22). Therefore, we cannot be certain whether HLA-B51 itself or a closely linked gene is responsible for the susceptibility to BD.…”

Section: Discussionmentioning

confidence: 99%

Association of MICA Polymorphism with HLA-B51 and Disease Severity in Korean Patients with Behcet's Disease

Park

Seo

et al. 2002

J Korean Med Sci

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The HLA-B51 allele is known to be associated with Behcet's disease (BD) in many ethnic group. However, it has not yet been clarified whether the HLA-B51 gene itself is the pathogenic gene related to BD or whether it is some other gene in linkage disequlibrium with HLA-B51. Recently, the Triplet repeat (GCT/AGC) polymorphism in transmembrane region of the MHC class I chain-related A (MICA) gene was identified. To investigate the association of MICA with BD, we studied the MICA polymorphism in 108 Korean BD patients and 204 healthy controls in relation to the presence of HLA-B51 and clinical manifestations. The triplet repeat polymorphism was determined by polymerase chain reaction (PCR)-denaturing polyacrylamide gel electrophoresis (PAGE). The phenotype frequency of the MICA*A6 allele (relative risk, RR=2.15, p=0.002) and HLA-B51(RR=1.87, p=0.022) were significantly increased in the Korean patients with BD. A strong linkage disequilibrium was observed between the MICA*A6 and HLA-B51 in both the patients with BD and control subjects. Stratification analysis showed that MICA*A6 homozygosity was strongly associated with BD in the HLA-B51-negative population, and HLA-B51 was also associated with MICA*A6-negative population. In conclusion, MICA*A6 rather than HLA-B51 was strongly associated with Korean patients with BD, and the MICA*A6 allele is a useful susceptibility marker of BD, especially in the HLA-B5-negative

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Section: Discussionmentioning

confidence: 99%

Association of MICA Polymorphism with HLA-B51 and Disease Severity in Korean Patients with Behcet's Disease

Park

Seo

et al. 2002

J Korean Med Sci

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“…In many populations, HLA-B5101 has been identified as the major subtype of HLA-B51 (González-Escribano et al, 1998;Mizuki et al, 2001;Paul et al, 2001). HLA-B5101 positivity has been reported to be 62-98% in various populations (Suzuki and Suzuki, 2004).…”

Section: Hla-b51 Subtypes In Behçet's Diseasementioning

confidence: 99%

HLA-B51 subtypes in Turkish patients with Behçet's disease and their correlation with clinical manifestations

Dd¹,

Gg²,

Akoğlu³

et al. 2014

Genet. Mol. Res.

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“…The genotype of HLA-B51 has been analyzed in BD patients in various countries [19][20][21][22][23][24][25]; 21 alleles were identified for HLA-B51 molecules, designated as HLA-B*5101 to B*5121. Studies in ten countries along the Silk Road disclosed that 26%-77% of patients were HLA-B51 positive.…”

Section: Hla-b51mentioning

confidence: 99%

Behcet’s disease

2004

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Behcet's disease (BD) is a systemic disorder of recurrent acute inflammation, characterized by major symptoms of oral aphthous ulcers, uveitis, skin lesions and genital ulcers. Involvement of intestines, vessels, and central nervous system (CNS) sometimes leads to a poor prognosis. Patients with BD are known to distribute along the ancient Silk Road. The incidence is relatively higher from eastern Asia to the Mediterranean area as roughly 1-10 patients in 10,000 people, whereas only 1-2 patients in 1,000,000 people in UK and North America. Although etiology of the disease is still unknown, high prevalence of HLA-B51, increased expression of heat shock protein 60 and Th1 dominant immune responses in the patients are considered important in its pathogenesis. Non-infectious neutrophil activation and infection with Streptococcus sanguis and herpes simplex virus would also be associated. Because BD lacks any pathognomonic symptoms and laboratory findings, the diagnosis relies largely upon the criteria proposed by the International Study Group for Behcet's disease in 1990. In Japan, the diagnosis was also made according to the Japanese criteria revised in 1987. Recently, the Behcet's Disease Research Committee of Japan again revised the Japanese criteria in 2003 to avoid overdiagnosis. The new Japanese criteria are introduced in this review. Differential diagnosis excluding Sweet's disease, pemphigus, erythema nodosum and Crohn's disease is important, and positive laboratory data for pathergy test, prick test for dead Streptococci and HLA-B51 are emphasized to make appropriate diagnosis in these criteria. Pathological findings of the disease-affected site such as erythematous nodosum is also stressed. Treatment for the disease has been chosen according to the clinical symptoms. Non-steroidal anti-inflammatory drugs, immunosuppressants, corticosteroids and colchicine are basically introduced. Recently, effects of interferon-alpha/beta, anti-tumor necrosis factor antibody and thalidomide are encouraging, specifically in treatment for the cases with poor prognosis including eye, intestine, vessel and CNS involvement. Low dose weekly administration of methotraxate looks effective for the cases with CNS involvement. Further studies for elucidation of the etiology, improvement of the diagnostic criteria and development of new therapy are needed to conquer the disease.

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HLA‐B51 allele analysis by the PCR‐SBT method and a strong association of HLA‐B5101 with Japanese patients with Behçet’s disease

Cited by 55 publications

References 13 publications

Association of MICA Polymorphism with HLA-B51 and Disease Severity in Korean Patients with Behcet's Disease

Association of MICA Polymorphism with HLA-B51 and Disease Severity in Korean Patients with Behcet's Disease

HLA-B51 subtypes in Turkish patients with Behçet's disease and their correlation with clinical manifestations

Behcet’s disease

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