RESEARCH - Smoking increases RA susceptibility in individuals carrying the HLA-DRB1 shared epitope

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Arthritis Rheum. 2010 Feb;62(2):369-77.

Smoking increases rheumatoid arthritis susceptibility in individuals

carrying the HLA-DRB1 shared epitope, regardless of rheumatoid factor

or anti-cyclic citrullinated peptide antibody status.

Bang SY, Lee KH, Cho SK, Lee HS, Lee KW, Bae SC.

Hospital for Rheumatic Diseases, Hanyang University, Seoul, South Korea.

Abstract

OBJECTIVE: Smoking is associated with rheumatoid arthritis (RA) in

individuals with the HLA-DRB1 shared epitope (SE). SE alleles have

been shown to be predominantly associated with anti-cyclic

citrullinated peptide (anti-CCP)-positive RA. These risk factors have

not been identified for anti-CCP-negative RA. The aim of this study

was to investigate whether SE-containing HLA-DRB1 alleles, smoking, or

the combination of these factors contributes to the development of RA,

depending on the presence or absence of serologic markers, in a Korean

population.

METHODS: All of the patients with RA (n =1,482) and all of the control

subjects (n = 1,119) were Korean. Four-digit HLA-DRB1 typing was

performed by a conventional polymerase chain reaction-sequence-based

typing method. Information about smoking history was obtained through

a questionnaire. The patients with RA were tested for anti-CCP

antibodies and rheumatoid factor (RF).

RESULTS: The SE alleles had significant effects on anti-CCP antibody

and RF formation. The DRB1*0901 allele was associated with the

presence of anti-CCP antibodies (odds ratio [OR] 2.49) and RF (OR

2.09). SE alleles and smoking were associated with both

anti-CCP-positive and anti-CCP-negative RA. The combination of smoking

and double copies of the SE allele increased the risk of

anti-CCP-positive RA 36.11-fold and increased the risk of

anti-CCP-negative RA 12.29-fold, compared with the risk among

nonsmokers not carrying SE alleles. Interactions between SE alleles

and smoking were observed for both anti-CCP-positive and RF-positive

RA, although the associations of RF-positive RA could be consequences

of the underlying anti-CCP antibody status.

CONCLUSION: We demonstrated that the combination of SE alleles and

smoking is associated with RA susceptibility regardless of anti-CCP

antibody or RF status, but that the combination shows stronger effects

in anti-CCP-positive/RF-positive patients with RA than in

anti-CCP-negative/RF-negative patients with RA. The SE-smoking

interactions were present in anti-CCP-positive and RF-positive RA.

PMID: 20112396

http://www.ncbi.nlm.nih.gov/pubmed/20112396

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