title: Genetics of Behçet's disease in Sardinia: two distinct extended HLA haplotypes harbour the B*51 allele in the normal population and in patients.
abstract: OBJECTIVE
  To define the contribution of HLA genes and extended HLA haplotypes to the susceptibility to Behçet's disease (BD) in Sardinia.
  
  
  METHODS
  Forty-five unrelated Sardinian patients with BD, diagnosed according to the ISG criteria, 45 HLA-B*51 positive and 185 unselected healthy controls were enrolled in the study. DNA samples were typed for HLA class I and class II alleles and genotyped for microsatellites (MICA-TM) and single-nucleotide polymorphisms (rs1264457 HLA-E; rs2281820 motilin; rs1799724 at -857, rs361525 at -238 TNF-alpha) spanning the HLA region.
  
  
  RESULTS
  HLA-B*5101 was confirmed as conferring susceptibility to BD (pc=0.0042; OR=4.4; 95% CI=2.0 to 9.6). It is noteworthy that in Sardinia this allele was found more frequently within a haplotype (HLA-A2; -Cw2; -B*5101; -DRB1*11; -DQA1*05; - DQB1*03) that reached its highest frequency in patients with BD. Linkage disequilibrium analysis showed the existence of an additional B*51 haplotype (HLA-A2; -Cw2; -B*5101; -DRB1*04; -DQA1*03; -DQB1*03) not associated with susceptibility to the disease.
  
  
  CONCLUSIONS
  In Sardinia, the BD-associated HLA-B*5101 allele is inherited as part of two distinctive haplotypes differently distributed in patients and controls. These findings can be interpreted as suggestive of the presence of additional genes within the MHC region conferring susceptibility to BD. The hypothesis that an environmental pressure could have contributed to the preservation of the BD-associated HLA haplotype in Sardinia is also discussed.
authors.affiliation: Rheumatology and Rheumatology Unit, University and AOU of Cagliari, Cagliari, Italy. matteopiga@alice.it
authors.forename: M
authors.initials: M
authors.lastname: Piga
authors.forename: F
authors.initials: F
authors.lastname: Paladini
authors.forename: S
authors.initials: S
authors.lastname: Lai
authors.forename: G
authors.initials: G
authors.lastname: Erre
authors.forename: G
authors.initials: G
authors.lastname: Passiu
authors.forename: C
authors.initials: C
authors.lastname: Carcassi
authors.forename: R
authors.initials: R
authors.lastname: Sorrentino
authors.forename: A
authors.initials: A
authors.lastname: Mathieu
mesh_terms: D001528:Behcet Syndrome / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D059949:HLA-B51 Antigen / Q000235:genetics*; D006239:Haplotypes; D040941:Heredity; D006801:Humans; D007558:Italy / Q000453:epidemiology; D015810:Linkage Disequilibrium; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D059949:HLA-B51 Antigen