RESEARCH - Gene-environment interaction between the DRB1 SE and smoking in the risk of anti-CCP-positive RA. All alleles are important.

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Arthritis Rheum. 2009 May 28;60(6):1597-1603.

Gene-environment interaction between the DRB1 shared epitope and

smoking in the risk of anti-citrullinated protein antibody-positive

rheumatoid arthritis: All alleles are important.

Lundström E, Källberg H, Alfredsson L, Klareskog L, Padyukov L.

Karolinska Institutet, Stockholm, Sweden.

OBJECTIVE: An interaction effect for developing rheumatoid arthritis

(RA) was previously observed between HLA-DRB1 shared epitope (SE)

alleles and smoking. We aimed to further investigate this interaction

between distinct SE alleles and smoking regarding the risk of

developing RA with and without anti-citrullinated protein antibodies

(ACPAs).

METHODS: We used data regarding smoking habits and HLA-DRB1 genotypes

from 1,319 patients and 943 controls from the Epidemiological

Investigation of Rheumatoid Arthritis, in which 972 patients and 488

controls were SE positive. Subsequently, 759 patients and 328 controls

were subtyped for specific alleles within the DRB1*04 group. Odds

ratios with 95% confidence intervals (95% CIs) were calculated by

means of logistic regression. Interaction was evaluated by calculating

attributable proportion due to interaction, with 95% CIs.

RESULTS: A strong interaction between smoking and SE alleles in the

development of ACPA-positive RA was observed for all DRB1*04 SE

alleles taken as a group (relative risk [RR] 8.7 [95% CI 5.7-13.1])

and for the *0401 and *0404 alleles (RR 8.9 [95% CI 5.8-13.5]) and the

*01 and *10 alleles (RR 4.9 [95% CI 3.0-7.8]) as specific, separate

groups, with similar strength of interaction for the different groups

(attributable proportion due to interaction 0.4 [95% CI 0.2-0.6], 0.5

[95% CI 0.3-0.7], and 0.6 [95% CI 0.4-0.8], respectively).

CONCLUSION: There is a statistically significant interaction between

distinct DRB1 SE alleles and smoking in the development of

ACPA-positive RA. Interaction occurs with the *04 group as well as the

*01/*10 group, demonstrating that regardless of fine specificity, all

SE alleles strongly interact with smoking in conferring an increased

risk of ACPA-positive RA.

PMID: 19479873

http://www.ncbi.nlm.nih.gov/pubmed/19479873

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