RESEARCH - Strong combined gene-environment effects in anti-CCP-positive RA

[Guest guest]

Arthritis Rheum. 2007 May;56(5):1446-53.

Strong combined gene-environment effects in anti-cyclic citrullinated

peptide-positive rheumatoid arthritis: a nationwide case-control study

in Denmark.

Pedersen M, sen S, Garred P, Madsen HO, Klarlund M, Svejgaard A,

Pedersen BV, Wohlfahrt J, Frisch M.

Danish Epidemiology Science Centre, Statens Serum Institut, Copenhagen, Denmark.

OBJECTIVE: To study the role of shared epitope (SE) susceptibility

genes, alone and in combination with tobacco smoking and other

environmental risk factors, for risk of subtypes of rheumatoid

arthritis (RA) defined by the presence or absence of serum antibodies

against cyclic citrullinated peptides (CCPs). METHODS: To address

these issues, a nationwide case-control study was conducted in Denmark

during 2002-2004, comprising incident cases of RA or patients with

recently diagnosed RA (309 seropositive and 136 seronegative for IgG

antibodies against CCP) and 533 sex- and age-matched population

controls. Associations were evaluated by logistic regression analyses,

in which odds ratios (ORs) served as measures of relative risk.

RESULTS: Compared with individuals without SE susceptibility genes, SE

homozygotes had an elevated risk of anti-CCP-positive RA (OR 17.8, 95%

confidence interval [95% CI] 10.8-29.4) but not anti-CCP-negative RA

(OR 1.07, 95% CI 0.53-2.18). Strong combined gene-environment effects

were observed, with markedly increased risks of anti-CCP-positive RA

in SE homozygotes who were heavy smokers (OR 52.6, 95% CI 18.0-154),

heavy coffee drinkers (OR 53.3, 95% CI 15.5-183), or oral

contraceptive users (OR 44.6, 95% CI 15.2-131) compared with SE

noncarriers who were not exposed to these environmental risk factors.

CONCLUSION: Persons who are homozygous for SE susceptibility genes,

notably those who are also exposed to environmental risk factors, have

a markedly and selectively increased risk of anti-CCP-positive RA. A

distinction between anti-CCP-positive RA and anti-CCP-negative RA

seems warranted, because these RA subtypes most likely represent

etiologically distinct disease entities.

PMID: 17469102

http://www.ncbi.nlm.nih.gov/pubmed/17469102

--

Not an MD