title: MICA rather than MICB, TNFA, or HLA-DRB1 is associated with susceptibility to psoriatic arthritis.
abstract: OBJECTIVE
  To analyze the genetic contribution of HLA in development of psoriatic arthritis (PsA) and to study whether MICA is primarily associated with PsA or whether its association is secondary to linkage disequilibrium with centromeric genes, such as MICB, TNFA, or HLA-DRB1.
  
  
  METHODS
  DNA samples from 81 Spanish patients with PsA and 110 healthy controls were examined by polymerase chain reaction (PCR) sequence-specific primers to type HLA-Cw and HLA-DRB1, PCR sequence-specific oligonucleotides to determine HLA-B, and PCR restriction fragment length polymorphism for tumor necrosis factor-alpha promoter polymorphisms at positions -238 and -308. Analysis of microsatellite polymorphisms in the transmembrane region of MICA and in intron 1 of MICB was also carried out.
  
  
  RESULTS
  HLA-Cw*0602 was significantly increased in PsA [60% vs 17%; p(c) < 0.00002, OR 7.33, etiological fraction (EF) 0.52]. MICA-A9 (60% vs 30%; p(c) = 0.0002, OR 3.57, EF 0.43) and the microsatellite MICB-CA-22 allele (23% vs 7%; p(c) = 0.028, OR 3.9, EF 0.17) were also significantly increased in PsA. MICA-A9 was in linkage disequilibrium with MICB-CA-22 (delta = 0.6). The association of MICA-A9 was independent of MICB-CA-22 and Cw*0602, since it was also associated in MICB-CA-22 negative (p(c) = 0.0015, OR 2.96, EF 0.34) and in Cw*0602 negative patients (p(c) = 0.034, OR 2.83, EF 0.34). TNFA and DRB I alleles were not significantly associated with PsA.
  
  
  CONCLUSIONS
  Cw*0602 and MICA-A9 appear to be the strongest genetic susceptibility factors for PsA. However, MICA-A9 was associated independently of Cw6. HLA-B alleles and MICB-CA22 are associated secondarily to linkage with MICA. TNFA and HLA-DRB1 were not associated with PsA susceptibility, and our data suggest that their reported association may only reflect the linkage disequilibrium with MICA-A9 among the different populations studied.
authors.affiliation: University of Oviedo, and Department of Immunology, Hospital Central de Asturias, Spain.
authors.forename: Segundo
authors.initials: S
authors.lastname: González
authors.forename: Jesús
authors.initials: J
authors.lastname: Martínez-Borra
authors.forename: Antonio
authors.initials: A
authors.lastname: López-Vázquez
authors.forename: Sonia
authors.initials: S
authors.lastname: García-Fernández
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Torre-Alonso
authors.forename: Carlos
authors.initials: C
authors.lastname: López-Larrea
mesh_terms: D000328:Adult; D015535:Arthritis, Psoriatic / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D015235:HLA-B Antigens / Q000235:genetics; D059945:HLA-B38 Antigen; D059946:HLA-B39 Antigen; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D015235:HLA-B Antigens; D059945:HLA-B38 Antigen; D059946:HLA-B39 Antigen; C103707:HLA-B57 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A; C098080:MICB antigen; D014409:Tumor Necrosis Factor-alpha