The objective of the proposed study is to assess the role of smoking and complex gene-smoking interactions in two understudied Rheumatoid Arthritis (RA)groups.
Rheumatoid Arthritis (RA) is a systemic inflammatory disease affecting over 2 million people in the U.S. alone, a condition characterized by progressive joint destruction, significant work-related disability and accelerated mortality. While the precise cause of RA is unknown, it is clear that the disease does not result from a single heritable factor or single environmental exposure. Of the many environmental exposures that have been studied, cigarette smoking is the factor most consistently shown to be associated with RA onset. In addition to its role in disease susceptibility, recent studies have found that smoking, along with genetic factors, contribute to RA-related autoimmunity and disease severity. Moreover, studies to date looking at disease severity in RA have exclusively involved women of Caucasian/European ancestry. This is an important distinction since although RA is more common in women, smoking appears to be most closely linked to RA risk in men. Additionally, the burden of other smoking-related illnesses appears to be greatest among non-Caucasian populations. For this reason and because smoking rates and prevalence of risk-alleles differ in ethnic/racial minorities (i.e. SE and GSTM1-null polymorphism), further studies are needed to define the association of smoking and possible gene-smoking interactions and their role in autoimmunity and disease severity in these understudied populations.
Study Type
OBSERVATIONAL
Enrollment
800
Omaha Veteran's Affairs Medical Center
Omaha, Nebraska, United States
Rheumatoid factor (RF) antibody status and concentration
Rheumatoid factor (RF) antibody status and concentration. RF is an autoantibody that responds to inflammation caused by RA.
Time frame: baseline
Anti-CCP antibody status and concentration
Anti-CCP (cyclic citrullinated peptide antibodies) antibody status and concentration. The normal level of anti-CCP antibodies is less than 20 units/mL. Anything over this level means a positive test. Anti-cyclic citrullinated peptide antibody titer predicts time to rheumatoid arthritis onset in patients with undifferentiated arthritis.
Time frame: baseline
Evidence of radiographic erosions and scoring.
Evidence of radiographic erosions and scoring. Erosions are graded from 0 to 4 (0 = normal; 1 = questionable; 2 = definite but mild; 3 = moderate; and 4 = severe). This method requires a standard reference set of radiographs for comparison. The range of erosion scores is from 0 to 128 in the hands, and from 0 to 48 in the feet.
Time frame: baseline
Smoking status and cotinine levels
Smoking status and cotinine levels are recorded. Cotinine is measured in nanograms per milliliter (ng/mL): Cotinine levels in a nonsmoker are generally less than 10 ng/mL. Cotinine levels in a light smoker or someone exposed to secondhand smoke are 11 ng/mL to 30 ng/mL. Cotinine levels in a heavy smoker may be more than 500 ng/mL.
Time frame: baseline
Genotyping of the FSTM1, NAT1, NAT2, and mDEH genes
Samples will be taken to genotype FSTM1, NAT1, NAT2, and mDEH genes which are important in carcinogenesis.
Time frame: baseline
Racial/ethnic composition and disease characteristics
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Both racial/ethnic composition and disease characteristics are recorded for analysis.
Time frame: baseline