Environmental Risk Factors Differ Between Rheumatoid Arthritis With and Without Auto-Antibodies Against Cyclic Citrullinated Peptides

Arthritis Res Ther. 2006;8(4):R133. doi: 10.1186/ar2022.

Abstract

The aim of this study was to evaluate new and previously hypothesised non-genetic risk factors for serologic subtypes of rheumatoid arthritis (RA) defined by the presence or absence of auto-antibodies to cyclic citrullinated peptides (CCP). In a national case-control study, we included 515 patients recently diagnosed with RA according to the American College of Rheumatology 1987 classification criteria and 769 gender- and age-matched population controls. Telephone interviews provided information about non-genetic exposures, and serum samples for patients were tested for anti-CCP-antibodies. Associations between exposure variables and risk of anti-CCP-positive and anti-CCP-negative RA were evaluated using logistic regression. A series of RA subtype-specific risk factors were identified. Tobacco smoking (odds ratio [OR] = 1.65; 95% confidence interval: 1.03-2.64, for > 20 versus 0 pack-years) was selectively associated with risk of anti-CCP-positive RA, whereas alcohol consumption exhibited an inverse dose-response association with this RA subtype (OR = 1.98, 1.22-3.19, for 0 versus > 0-5 drinks per week). Furthermore, coffee consumption (OR = 2.18; 1.07-4.42, for > 10 versus 0 cups per day), ever use of oral contraceptives (OR = 1.65; 1.06-2.57) and having a first-degree relative with schizophrenia (OR = 4.18; 1.54-11.3) appeared more strongly associated with risk of anti-CCP-positive RA. Obesity was selectively associated with risk of anti-CCP-negative RA, with obese individuals being at more than 3-fold increased risk of this subtype compared with normal-weight individuals (OR = 3.45; 1.73-6.87). Age at menarche was the only examined factor that was significantly associated with both serologic subtypes of RA (p-trends = 0.01); women with menarche at age > or = 15 years had about twice the risk of either RA subtype compared with women with menarche at age < or = 12 years. Major differences in risk factor profiles suggest distinct etiologies for anti-CCP-positive and anti-CCP-negative RA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Animals
  • Animals, Domestic
  • Antibodies / blood*
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / complications
  • Arthritis, Rheumatoid / etiology
  • Arthritis, Rheumatoid / immunology*
  • Asthma / complications
  • Coffee
  • Contraceptives, Oral / adverse effects
  • Drinking
  • Environment*
  • Female
  • Humans
  • Male
  • Marital Status
  • Medical Records
  • Menarche
  • Middle Aged
  • Peptides, Cyclic / immunology*
  • Risk Factors
  • Schizophrenia / genetics
  • Sexual Behavior

Substances

  • Antibodies
  • Coffee
  • Contraceptives, Oral
  • Peptides, Cyclic
  • cyclic citrullinated peptide