RESEARCH - Associations between genetic factors, tobacco smoking and autoantibodies in familial and sporadic RA

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Published Online First: 27 July 2007. doi:10.1136/ard.2007.075622

ls of the Rheumatic Diseases 2008;67:466-470

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EXTENDED REPORTS

Associations between genetic factors, tobacco smoking and

autoantibodies in familial and sporadic rheumatoid arthritis

L Michou 1,2, V H Teixeira 1,3, C Pierlot 1, S Lasbleiz 1,4, T Bardin

1,2, P Dieudé 1,5, B Prum 6, F Cornélis 1,4,7, E Petit-Teixeira 1

1 GenHotel-EA 3886, Universités Evry-ParisVII, Evry-Genopole, France

2 Fédération de rhumatologie, Hôpital Lariboisière, Pôle appareil

locomoteur, Assistance Publique-Hôpitaux de Paris, Paris, France

3 Faculty of Medicine, University of Coimbra, Coimbra, Portugal

4 Unité de Génétique Clinique Adulte, Hôpital Lariboisière, Pôle

biologie-imagerie-pharmacie, Assistance Publique-Hôpitaux de Paris,

France

5 Service de rhumatologie, Hôpital Bichat, Assistance

Publique-Hôpitaux de Paris, France

6 Laboratoire Statistique et Génome, Evry-Genopole, France

7 Consultation de Génétique Adulte, Centre Hospitalier Sud Francilien,

Evry-Corbeil, France

Objectives: The objective of this study was to investigate the

association between genes (HLA-DRB1 and PTPN22) and tobacco smoking,

separately as well as combined, and serological markers of rheumatoid

arthritis (RA) in a French population with RA.

Methods: 274 patients with RA with half of them belonging to RA

multicase families, were genotyped for HLA-DRB1 allele and for

PTPN22-1858 polymorphism. IgM rheumatoid factor and anti-cyclic

citrullinated peptide (anti-CCP) antibodies were determined by ELISA

method. The search for association relied on 2 test and odds ratio

with 95% confidence interval calculation. The interaction study relied

on the departure-from-additivity-based method.

Results: The presence of at least one shared epitope (SE) allele was

associated with anti-CCP antibodies presence (82.5% vs. 68.4%, p =

0.02), particularly with HLA-DRB1*0401 allele (28.0% vs. 16.4%, p =

0.01). Tobacco exposure was associated with anti-CCP antibodies, but

only in presence of SE. A tendency toward an interaction was found

between tobacco, the presence of at least one HLA-DRB1*0401 allele and

anti-CCP antibodies (attributable proportion due to interaction =

+0.24 (–0.21+0.76)). The cumulative dose of cigarette smoking was

correlated with anti-CCP antibody titres (r = 0.19, p = 0.04). The

presence of both SE and 1858T alleles was associated with a higher,

but not significantly different, risk for anti-CCP antibodies presence

than for each separately. No association was found between

PTPN22-1858T allele and tobacco smoking for autoantibody positivity.

Conclusions: Our findings suggest an association between SE alleles

and tobacco smoking for anti-CCP positivity and a tendency toward an

interaction between the HLA-DRB1*0401 allele and smoking for anti-CCP

positivity in this sample of RA.

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http://ard.bmj.com/cgi/content/abstract/67/4/466

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