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Genetics of Behçet’s Disease

  • Ahmet Gül
  • Shigeaki Ohno
Chapter

Abstract

Behçet’s disease (BD) is a multifactorial disease with a strong genetic background. Varying frequencies of patients with a positive family history for BD were described with a tendency for higher figures in the Middle Eastern, juvenile-onset and HLA-B51 positive patients. Sibling recurrence risk ratio (λs) was calculated to be 11.4–52.5 for BD patients in Turkey. BD is strongly associated with a class I major histocompatibility complex (MHC) allele, HLA-B51, and this association was confirmed in various ethnic groups. Distribution of HLA-B51 allele in healthy population is suggested to play a role in the disease clustering in an area extending from the Mediterranean basin to Japan. The pathogenic mechanisms of HLA-B51 are still unknown, but it may include presentation of specific peptides to CD8+ cells and interaction with KIR3DL1 receptors. Although contribution of the HLA-B locus to the overall BD susceptibility was estimated to be 19%, other MHC associations including HLA-A26 and MICA*009 may have additive effects. Association studies also suggested several non-HLA disease susceptibility genes. However, only a few of them, including polymorphisms in the TNF, MEFV, ICAM1, and eNOS genes, were replicated in different ethnic groups. A linkage study in multicase families of Turkish origin revealed several possible susceptibility loci for BD with >3.0 nonparametric linkage scores at chromosome 12p12-13, 6p22-24, and 6q25-26. Recent genomewide association study using microsatellite markers in Japanese patients and controls confirmed the loci at 12p12 and 6q25, and it also suggested two additional loci at 3p12 and 22q11.22. Currently, results of genomewide association studies from different ethnic groups are being awaited to clarify the genetics of BD further.

Keywords

Behçet’s disease Familial aggregation Sibling recurrence risk ratio (λs) HLA-B51 MICA HLA-A26 Linkage study Genomewide association study 

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© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Internal Medicine, Division of Rheumatology, Istanbul Faculty of MedicineIstanbul UniversityIstanbulTurkey

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