Environmental risk factors differ between rheumatoid arthritis with and without auto-antibodies against cyclic citrullinated peptides.
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.
Pedersen
Merete
M
Department of Epidemiology Research, Danish Epidemiology Science Centre, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark. mtb@ssi.dk
Jacobsen
Søren
S
Klarlund
Mette
M
Pedersen
Bo V
BV
Wiik
Allan
A
Wohlfahrt
Jan
J
Frisch
Morten
M
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000818:Animals; D000829:Animals, Domestic; D000906:Antibodies / Q000097:blood*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000150:complications / Q000209:etiology / Q000276:immunology*; D001249:Asthma / Q000150:complications; D003069:Coffee; D003276:Contraceptives, Oral / Q000009:adverse effects; D004326:Drinking; D004777:Environment; D005260:Female; D006801:Humans; D008297:Male; D017533:Marital Status; D008499:Medical Records; D008572:Menarche; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D012307:Risk Factors; D012559:Schizophrenia / Q000235:genetics; D012725:Sexual Behavior
D000906:Antibodies; D003069:Coffee; D003276:Contraceptives, Oral; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide