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Smoking increases rheumatoid arthritis susceptibility in individuals carrying the HLA-DRB1 shared epitope, regardless of rheumatoid factor or anti-cyclic citrullinated peptide antibody status.

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.

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  • Authors+Show Affiliations

    ,

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

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    Source

    Arthritis and rheumatism 62:2 2010 Feb pg 369-77

    MeSH

    Adult
    Alleles
    Arthritis, Rheumatoid
    Biomarkers
    Case-Control Studies
    Environment
    Epitopes
    Female
    Genetic Predisposition to Disease
    Genotype
    HLA-DR Antigens
    HLA-DRB1 Chains
    Humans
    Logistic Models
    Male
    Middle Aged
    Peptides, Cyclic
    Rheumatoid Factor
    Risk Factors
    Smoking

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    20112396

    Citation

    Bang, So-Young, et al. "Smoking Increases Rheumatoid Arthritis Susceptibility in Individuals Carrying the HLA-DRB1 Shared Epitope, Regardless of Rheumatoid Factor or Anti-cyclic Citrullinated Peptide Antibody Status." Arthritis and Rheumatism, vol. 62, no. 2, 2010, pp. 369-77.
    Bang SY, Lee KH, Cho SK, et al. Smoking increases rheumatoid arthritis susceptibility in individuals carrying the HLA-DRB1 shared epitope, regardless of rheumatoid factor or anti-cyclic citrullinated peptide antibody status. Arthritis Rheum. 2010;62(2):369-77.
    Bang, S. Y., Lee, K. H., Cho, S. K., Lee, H. S., Lee, K. W., & Bae, S. C. (2010). Smoking increases rheumatoid arthritis susceptibility in individuals carrying the HLA-DRB1 shared epitope, regardless of rheumatoid factor or anti-cyclic citrullinated peptide antibody status. Arthritis and Rheumatism, 62(2), pp. 369-77. doi:10.1002/art.27272.
    Bang SY, et al. Smoking Increases Rheumatoid Arthritis Susceptibility in Individuals Carrying the HLA-DRB1 Shared Epitope, Regardless of Rheumatoid Factor or Anti-cyclic Citrullinated Peptide Antibody Status. Arthritis Rheum. 2010;62(2):369-77. PubMed PMID: 20112396.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Smoking increases rheumatoid arthritis susceptibility in individuals carrying the HLA-DRB1 shared epitope, regardless of rheumatoid factor or anti-cyclic citrullinated peptide antibody status. AU - Bang,So-Young, AU - Lee,Kyoung-Ho, AU - Cho,Soo-Kyung, AU - Lee,Hye-Soon, AU - Lee,Kyung Wha, AU - Bae,Sang-Cheol, PY - 2010/1/30/entrez PY - 2010/1/30/pubmed PY - 2010/3/30/medline SP - 369 EP - 77 JF - Arthritis and rheumatism JO - Arthritis Rheum. VL - 62 IS - 2 N2 - 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. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/20112396/full_citation L2 - https://doi.org/10.1002/art.27272 DB - PRIME DP - Unbound Medicine ER -