RESEARCH - Smoking interacts with genetic risk factors in the development of RA among older Caucasian women

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Ann Rheum Dis. 2006 Sep;65(9):1163-7. Epub 2006 Aug 3.

Smoking interacts with genetic risk factors in the development of rheumatoid

arthritis among older Caucasian women.

Criswell LA, Saag KG, Mikuls TR, Cerhan JR, Merlino LA, Lum RF, Pfeiffer KA,

Woehl B, Seldin MF.

Division of Rheumatology, University of California, San Francisco, 374

Parnassus Avenue, Box 0500, San Francisco, CA 94143-0500, USA.

Lindsey.Criswell@....

OBJECTIVE: To determine whether the impact of tobacco exposure on rheumatoid

arthritis (RA) risk is influenced by polymorphisms at the HLA-DRB1 and

glutathione S-transferase M1 (GSTM1) loci. METHODS: SUBJECTS: were

participants from a case-control study nested within the Iowa Women's Health

Study, a population based, prospective cohort study of postmenopausal women.

Incident RA cases (n = 115) were identified and medical records reviewed to

confirm RA diagnosis. Controls without RA (n = 466) were matched with RA

cases by age and ethnic background. HLA-DRB1 typing classified subjects

according to the presence of alleles encoding the RA " shared epitope " (SE)

sequence. GSTM1 was genotyped using a multiplex polymerase chain reaction

assay. Conditional logistic regression was used to estimate the odds ratios

(ORs) and 95% confidence intervals. RESULTS: Strong positive associations of

smoking (OR = 6.0, p = 0.004), SE positivity (OR = 4.6, p = 0.0006), and

GSTM1 null genotype (OR = 3.4, p = 0.007) with risk of RA, and significant

gene-environment interactions (smoking by SE interaction p = 0.034; smoking

by GSTM1 interaction p = 0.047) were observed. Stratified analyses indicated

that exposure to tobacco smoke primarily increased the risk of RA among

subjects who lacked genetic risk factors for the disease (that is, SE

negative or GSTM1 present).

CONCLUSIONS: Although these findings require confirmation in other groups,

the results support the importance of considering both genetic and

environmental factors, and also their interaction, in studies of complex

diseases like RA.

PMID: 16887863

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

6887863

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