title: Effects of smoking and shared epitope on the production of anti-citrullinated peptide antibody in a Japanese adult population.
abstract: OBJECTIVE
  Anti-citrullinated peptide antibody (ACPA) and rheumatoid factor (RF) are markers to rheumatoid arthritis (RA). Smoking and shared epitope (SE) in HLA-DRB1 are associated with the production of these autoantibodies in RA. Detailed distribution and characterization of ACPA and RF in the general population have remained unclear. We aimed to evaluate positivity of ACPA and RF in a general Japanese population and to detect correlates, including genetic components.
  
  
  METHODS
  ACPA and RF were quantified in 9,804 Japanese volunteers ages 30-75 years. Logistic regression analyses were performed to evaluate the effects of candidates of correlates on the autoantibody positivity. A genome-wide association study (GWAS) was performed using 394,239 single nucleotide polymorphisms for 3,170 participants, and HLA-DRB1 alleles were imputed based on the GWAS data.
  
  
  RESULTS
  A total of 1.7% and 6.4% of subjects were positive for ACPA and RF, respectively, and the 2 markers showed a significant correlation (P = 2.0 × 10(-23) ). Old age was associated with ACPA positivity (P = 0.00062). Sex, smoking, SE, and other candidates of correlates did not have significant effects. Interaction between smoking and SE positivity was not apparent, but smoking showed a significant association with high levels of ACPA (P = 0.0019).
  
  
  CONCLUSIONS
  ACPA and RF could be detected in 1.7% and 6.4% of the Japanese adult population without RA, respectively. ACPA and RF were suggested to share mechanisms even in healthy populations. Old age was associated with increasing ACPA positivity. While positivity of ACPA and RF was not associated with SE and smoking, an association between high ACPA and smoking was observed.
authors.affiliation: Kyoto University, Kyoto, Japan.
authors.forename: Chikashi
authors.initials: C
authors.lastname: Terao
authors.forename: Koichiro
authors.initials: K
authors.lastname: Ohmura
authors.forename: Katsunori
authors.initials: K
authors.lastname: Ikari
authors.forename: Takahisa
authors.initials: T
authors.lastname: Kawaguchi
authors.forename: Meiko
authors.initials: M
authors.lastname: Takahashi
authors.forename: Kazuya
authors.initials: K
authors.lastname: Setoh
authors.forename: Takeo
authors.initials: T
authors.lastname: Nakayama
authors.forename: Shinji
authors.initials: S
authors.lastname: Kosugi
authors.forename: Akihiro
authors.initials: A
authors.lastname: Sekine
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Tabara
authors.forename: Atsuo
authors.initials: A
authors.lastname: Taniguchi
authors.forename: Shigeki
authors.initials: S
authors.lastname: Momohara
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yamanaka
authors.forename: Ryo
authors.initials: R
authors.lastname: Yamada
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Matsuda
authors.forename: Tsuneyo
authors.initials: T
authors.lastname: Mimori
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People; D001323:Autoantibodies / Q000235:genetics* / Q000276:immunology; D000939:Epitopes; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide; D012907:Smoking / Q000453:epidemiology*
chemical_list: D001323:Autoantibodies; D000939:Epitopes; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide