title: Brief report: association of CCR1, KLRC4, IL12A-AS1, STAT4, and ERAP1 With Behçet's disease in Iranians.
abstract: OBJECTIVE
  To independently replicate the top findings from 4 published genome-wide association studies (GWAS) of susceptibility genes in Behçet's disease (BD).
  
  
  METHODS
  We tested 14 single-nucleotide polymorphisms (SNPs) in 13 genomic loci (excluding the major histocompatibility complex [MHC], IL10, and IL23R-IL12RB2, which have already been associated with BD in Iranians) for allelic and genotypic associations with BD in 973 patients and 828 controls from Iran and performed meta-analyses of the significantly associated markers.
  
  
  RESULTS
  Six SNPs (in decreasing order of significance, rs7616215 located 38 kb downstream of CCR1, rs2617170 [p.Asn104Ser] in KLRC4, rs17810546 in IL12A-AS1, rs7574070 in STAT4, and rs10050860 [p.Asp575Asn] and rs13154629 in ERAP1) were nominally associated with BD in both allelic association tests (5.05 × 10(-9) ≤ Pallele ≤ 7.55 × 10(-3) ) and sex-adjusted genotypic association tests (6.01 × 10(-9) ≤ adjusted P value ≤ 1.30 × 10(-2) ). For all 6 SNPs tested by meta-analysis (Pmeta ), the association with BD was strengthened, because the direction and magnitude of association were similar across populations (e.g., for rs7574070, odds ratio [OR] for A allele 1.29 [95% confidence interval (95% CI) 1.21-1.37], Pmeta  = 2.34 × 10(-16) ; for rs7616215, OR for C allele 0.70 [95% CI 0.65-0.76], Pmeta  = 1.54 × 10(-19) ; for rs17810546, OR for A allele 0.60 [95% CI 0.52-0.70], Pmeta  = 6.34 × 10(-11) ; for rs2617170, OR for T allele 0.76 [95% CI 0.70-0.81], Pmeta  = 2.75 × 10(-14) ; for rs13154629, OR for TT genotype 2.76 [95% CI 2.01-3.80], Pmeta  = 3.57 × 10(-10) ).
  
  
  CONCLUSIONS
  This study reinforces the notion that CCR1, KLRC4, IL12A-AS1, STAT4, and ERAP1 are bona fide susceptibility genes for BD, in addition to the MHC, IL10, and IL23R-IL12RB2 loci. Future genetic and functional studies are now warranted to uncover the roles of these genes in the pathogenesis of BD.
authors.affiliation: Instituto de Medicina Molecular and Universidade de Lisboa, Lisbon, Portugal, and Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: Inês
authors.initials: I
authors.lastname: Sousa
authors.affiliation: Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Farhad
authors.initials: F
authors.lastname: Shahram
authors.affiliation: Instituto de Medicina Molecular and Universidade de Lisboa, Lisbon, Portugal, and Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: David
authors.initials: D
authors.lastname: Francisco
authors.affiliation: Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Fereydoun
authors.initials: F
authors.lastname: Davatchi
authors.affiliation: Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Bahar Sadeghi
authors.initials: BS
authors.lastname: Abdollahi
authors.affiliation: Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Fahmida
authors.initials: F
authors.lastname: Ghaderibarmi
authors.affiliation: Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Abdolhadi
authors.initials: A
authors.lastname: Nadji
authors.affiliation: Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Niloofar
authors.initials: N
authors.lastname: Mojarad Shafiee
authors.affiliation: Instituto de Medicina Molecular and Universidade de Lisboa, Lisbon, Portugal, and Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: Joana M
authors.initials: JM
authors.lastname: Xavier
authors.affiliation: Instituto de Medicina Molecular and Universidade de Lisboa, Lisbon, Portugal, and Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: Sofia A
authors.initials: SA
authors.lastname: Oliveira
mesh_terms: D000328:Adult; D000483:Alleles; D000626:Aminopeptidases / Q000235:genetics*; D001528:Behcet Syndrome / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D053765:Interleukin-12 Subunit p35 / Q000235:genetics*; D007492:Iran / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D054389:Receptors, CCR1 / Q000235:genetics*; D050797:STAT4 Transcription Factor / Q000235:genetics*
chemical_list: C515300:CCR1 protein, human; C508858:IL12A protein, human; D053765:Interleukin-12 Subunit p35; C527066:KLRC4 protein, human; D015778:Minor Histocompatibility Antigens; D055654:NK Cell Lectin-Like Receptor Subfamily C; D054389:Receptors, CCR1; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; D000626:Aminopeptidases; C464841:ERAP1 protein, human