Rheumatoid Arthritis
Conditions
Keywords
rheumatoid arthritis, cigarette smoking, gene-environmental interactions, autoimmunity, disease severity
Brief summary
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.
Detailed description
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.
Interventions
None listed
Sponsors
University of Alabama at Birmingham
University of Colorado, Denver
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
University of Nebraska
Study design
Observational model
COHORT
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Meeting ACR criteria for RA
Exclusion criteria
* No exclusions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rheumatoid factor (RF) antibody status and concentration | baseline | Rheumatoid factor (RF) antibody status and concentration. RF is an autoantibody that responds to inflammation caused by RA. |
| Anti-CCP antibody status and concentration | baseline | 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. |
| Evidence of radiographic erosions and scoring. | baseline | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Smoking status and cotinine levels | baseline | 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. |
| Genotyping of the FSTM1, NAT1, NAT2, and mDEH genes | baseline | Samples will be taken to genotype FSTM1, NAT1, NAT2, and mDEH genes which are important in carcinogenesis. |
| Racial/ethnic composition and disease characteristics | baseline | Both racial/ethnic composition and disease characteristics are recorded for analysis. |
Countries
United States
Outcome results
None listed