Gene-Environment Interactions in Rheumatoid Arthritis Autoimmunity Disease Severity

Gene-Environment Interactions in RA Autoimmunity Disease Severity

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.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis

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.

• Study Type: Observational
• Enrollment (Actual): 800

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Omaha, Nebraska, United States, 68105
      • Omaha Veteran's Affairs Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Omaha VA patients

Description

Inclusion Criteria:

• Meeting ACR criteria for RA

Exclusion Criteria:

• No exclusions

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
I Multicenter Veteran's Affairs Rheumatoid Arthritis (VARA) registry; multicenter Veteran Affairs Rheumatoid Arthritis (VARA) registry
II NIH-funded Consortium for the Longitudinal Evaluation of African Americans with Early RA (CLEAR); NIH-funded Consortium for the Longitudinal Evaluation of African Americans with Early RA (CLEAR)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	baseline
Racial/ethnic composition and disease characteristics	Both racial/ethnic composition and disease characteristics are recorded for analysis.	baseline

Collaborators and Investigators

• Sponsor: University of Nebraska
• Collaborators: University of Colorado, Denver; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); University of Alabama at Birmingham
• Investigators: Principal Investigator: Ted R Mikuls, MD, MSPH, University of Nebraska

Publications and helpful links

Helpful Links

• National Institute of Health

Study record dates

Study Major Dates

• Study Start (Actual): October 19, 2006
• Primary Completion (Actual): April 1, 2010
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: January 3, 2008
• First Submitted That Met QC Criteria: January 3, 2008
• First Posted (Estimated): January 15, 2008

Study Record Updates

• Last Update Posted (Actual): September 1, 2023
• Last Update Submitted That Met QC Criteria: August 29, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: rheumatoid arthritis; disease severity; autoimmunity; cigarette smoking; gene-environmental interactions
• Additional Relevant MeSH Terms: Immune System Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Autoimmune Diseases
• Other Study ID Numbers: 0358-06-NH; 1R03AR054539-01 (U.S. NIH Grant/Contract)