title: Association of HLA-C3 and smoking with vasculitis in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  To compare HLA-C genotypes and smoking habits in patients with vasculitis or other severe extraarticular manifestations of rheumatoid arthritis (ExRA) with those in RA patients without extraarticular disease.
  
  
  METHODS
  Patients were recruited from a large research database of patients with RA at the Mayo Clinic, from 2 Swedish cohorts of prevalent RA cases, and from a regional Swedish early RA cohort. Patients with severe ExRA (n = 159) and control patients with RA but no history of ExRA (non-ExRA controls) (n = 178) were matched for duration of RA and for clinical center. Data on smoking at RA onset, rheumatoid factor (RF) status, and antinuclear antibodies (ANAs) were extracted from the medical records. Polymerase chain reaction-based HLA-C genotyping was performed using a sequence-specific primer kit.
  
  
  RESULTS
  The distribution of HLA-C alleles was significantly different between patients with RA-associated vasculitis and non-ExRA controls (P = 0.014). This was mainly due to a positive association of the HLA-C3 allele with vasculitis (allele frequency 0.411 in vasculitis patients versus 0.199 in non-ExRA controls; P < 0.001) and a decreased frequency of HLA-C7 (0.122 and 0.243, respectively; P = 0.018). The association between HLA-C3 and vasculitis was not due to linkage disequilibrium with HLA-DRB1. Smoking (P = 0.001), RF positivity (P < 0.0001), and presence of ANAs (P < 0.0001) were all associated with ExRA. HLA-C3 and smoking were both significant predictors of vasculitis in a multivariate model.
  
  
  CONCLUSIONS
  Vasculitis in RA is associated with HLA-C3. Smoking is an independent predictor of vasculitis and other types of severe ExRA. Our results suggest that these variables are among the genetic and environmental factors that contribute significantly to the pathomechanisms of systemic RA.
authors.affiliation: Department of Rheumatology, Malmö University Hospital, Malmö, Sweden. turesson.carl@mayo.edu
authors.forename: Carl
authors.initials: C
authors.lastname: Turesson
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Schaid
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: Weyand
authors.forename: Lennart T
authors.initials: LT
authors.lastname: Jacobsson
authors.forename: Jörg J
authors.initials: JJ
authors.lastname: Goronzy
authors.forename: Ingemar F
authors.initials: IF
authors.lastname: Petersson
authors.forename: Sonja A
authors.initials: SA
authors.lastname: Dechant
authors.forename: Britt-Marie
authors.initials: BM
authors.lastname: Nyähll-Wåhlin
authors.forename: Lennart
authors.initials: L
authors.lastname: Truedsson
authors.forename: Gunnar
authors.initials: G
authors.lastname: Sturfelt
authors.forename: Eric L
authors.initials: EL
authors.lastname: Matteson
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000276:immunology* / Q000503:physiopathology; D005260:Female; D005838:Genotype; D015236:HLA-C Antigens / Q000097:blood* / Q000235:genetics; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D012907:Smoking / Q000097:blood* / Q000276:immunology; D014657:Vasculitis / Q000097:blood* / Q000150:complications / Q000276:immunology
chemical_list: D015236:HLA-C Antigens