title: Characterization of the major histocompatibility complex locus association with Behçet's disease in Iran.
abstract: BACKGROUND
  The aim of this study was to characterize the association of human leukocyte antigen (HLA) B alleles and major histocompatibility complex (MHC) single nucleotide polymorphisms (SNPs) with Behçet's disease (BD) in an Iranian dataset.
  
  
  METHODS
  The association of three SNPs in the MHC region previously identified as the most associated in high-density genotyping studies was tested in a case-control study on 973 BD patients and 825 controls from Iran, and the association of HLA-B alleles was tested in a subset of 681 patients and 414 controls.
  
  
  RESULTS
  We found that HLA-B*51 (P = 4.11 × 10(-41), OR [95% CI] = 4.63[3.66-5.85]) and B*15 confer risk for BD (P = 2.83 × 10(-2), OR [95% CI] = 1.75[1.08-2.84]) in Iranian, and in B*51 negative individuals, only the B*15 allele is significantly associated with BD (P = 2.51 × 10(-3), OR [95% CI] = 2.40[1.37-4.20]). rs76546355, formerly known as rs116799036, located between HLA-B and MICA (MHC class I polypeptide-related sequence A), demonstrated the same level of association with BD as HLA-B*51 (P adj = 1.78 × 10(-46), OR [95% CI] = 5.46[4.21-7.09], and P adj = 8.34 × 10(-48), OR [95% CI] = 5.44[4.20-7.05], respectively) in the HLA-B allelotyped subset, while rs2848713 was less associated (P adj = 7.14 × 10(-35), OR [95% CI] = 3.73[2.97-4.69]) and rs9260997 was not associated (P adj = 1.00 × 10(-1)). Additionally, we found that B*51 genotype-phenotype correlations do not survive Bonferroni correction, while carriers of the rs76546355 risk allele predominate in BD cases with genital ulcers, positive pathergy test and positive BD family history (2.31 × 10(-4) ≤ P ≤ 1.59 × 10(-3)).
  
  
  CONCLUSIONS
  We found that the HLA-B*51 allele and the rs76546355/rs116799036 MHC SNP are independent genetic risk factors for BD in Iranian, and that positivity for the rs76546355/rs116799036 risk allele, but not for B*51, does correlate with specific demographic characteristics or clinical manifestations in BD patients.
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, Edifício Egas Moniz, 1649-028, Lisboa, Portugal. jxavier@fm.ul.pt.|Instituto Gulbenkian de Ciência, Oeiras, Portugal. jxavier@fm.ul.pt.
authors.forename: Joana M
authors.initials: JM
authors.lastname: Xavier
authors.affiliation: Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran. fddh@neda.net.
authors.forename: Fereydoun
authors.initials: F
authors.lastname: Davatchi
authors.affiliation: Lisbon Center for Blood and Transplantation, Instituto Português de Sangue e Transplantação, Lisboa, IP, Portugal. olga.abade@ipst.min-saude.pt.
authors.forename: Olga
authors.initials: O
authors.lastname: Abade
authors.affiliation: Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran. shahram@neda.net.
authors.forename: Farhad
authors.initials: F
authors.lastname: Shahram
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, Edifício Egas Moniz, 1649-028, Lisboa, Portugal. vfrancisco@medicina.ulisboa.pt.|Instituto Gulbenkian de Ciência, Oeiras, Portugal. vfrancisco@medicina.ulisboa.pt.
authors.forename: Vânia
authors.initials: V
authors.lastname: Francisco
authors.affiliation: Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran. bahar@bahars.net.
authors.forename: Bahar Sadeghi
authors.initials: BS
authors.lastname: Abdollahi
authors.affiliation: Lisbon Center for Blood and Transplantation, Instituto Português de Sangue e Transplantação, Lisboa, IP, Portugal. helder.trindade@ipst.min-saude.pt.
authors.forename: Hélder
authors.initials: H
authors.lastname: Trindade
authors.affiliation: Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran. naji_rrc@yahoo.com.
authors.forename: Abdolhadi
authors.initials: A
authors.lastname: Nadji
authors.affiliation: Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran. n.mshafiee@yahoo.com.
authors.forename: Niloofar Mojarad
authors.initials: NM
authors.lastname: Shafiee
authors.affiliation: Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran. famida_gh@yahoo.com.
authors.forename: Fahmida
authors.initials: F
authors.lastname: Ghaderibarmi
authors.affiliation: Lisbon Center for Blood and Transplantation, Instituto Português de Sangue e Transplantação, Lisboa, IP, Portugal. dario@ipst.min-saude.pt.
authors.forename: Dário
authors.initials: D
authors.lastname: Ligeiro
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, Edifício Egas Moniz, 1649-028, Lisboa, Portugal. aaoliveira@medicina.ulisboa.pt.|Instituto Gulbenkian de Ciência, Oeiras, Portugal. aaoliveira@medicina.ulisboa.pt.
authors.forename: Sofia A
authors.initials: SA
authors.lastname: Oliveira
mesh_terms: D000328:Adult; D001528:Behcet Syndrome / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies / Q000379:methods; D056426:Genetic Loci / Q000235:genetics*; D059949:HLA-B51 Antigen / Q000235:genetics*; D006801:Humans; D007492:Iran / Q000453:epidemiology; D008285:Major Histocompatibility Complex / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D059949:HLA-B51 Antigen