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Open Access Highly Accessed Research article

Environmental risk factors differ between rheumatoid arthritis with and without auto-antibodies against cyclic citrullinated peptides

Merete Pedersen1*, Søren Jacobsen2, Mette Klarlund2, Bo V Pedersen1, Allan Wiik3, Jan Wohlfahrt1 and Morten Frisch1

  • * Corresponding author: Merete Pedersen mtb@ssi.dk

Author Affiliations

1 Department of Epidemiology Research, Danish Epidemiology Science Centre, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark

2 Department of Rheumatology, University Hospital of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark

3 Department of Autoimmunology, Statens Serum Institut, Artillerivej 5, DK-2300, Copenhagen S, Denmark

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Arthritis Research & Therapy 2006, 8:R133  doi:10.1186/ar2022

Published: 27 July 2006

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 ≥ 15 years had about twice the risk of either RA subtype compared with women with menarche at age ≤ 12 years. Major differences in risk factor profiles suggest distinct etiologies for anti-CCP-positive and anti-CCP-negative RA.