Relationship of YWHAH Polymorphisms to Rheumatoid Arthritis Disease Severity

Completed

• Conditions: Rheumatoid Arthritis
• Interventions: Diagnostic Test: TaqMan SNP analysis

• Registration Number: NCT03190746
• Lead Sponsor: Keesler Air Force Base Medical Center

Brief Summary

It is hypothesized that one or several of these 6 single nucleotide polymorphisms (SNPs) (rs2246704, rs2853884, rs3747158, rs4820059, rs7291050, and rs933226) in the YWHAH gene could be related to RA disease severity.

Detailed Description

Rheumatoid Arthritis (RA) is a chronic inflammatory arthritis of substantial morbidity. Serum biomarkers such as Rheumatoid Factor and anti-cyclic citrullinated peptide assist with disease diagnosis and prognostic assessment of future disease activity. 14-3-3 eta is a relatively new RA serum biomarker. The 14-3-3 family of proteins were named based on chromatographic elution properites and are ubiquitously expressed intracellular chaperon proteins. The isoform relevant in RA is 14-3-3 eta. 14-3-3 eta provides additional information about RA to the clinician-it assists in making diagnosis, provides prognostic assessment of disease severity, and provides insight regarding response to therapy. Thus, 14-3-3 eta serves as an important mechanistic biomarker informing the clinician about patient's RA.

14-3-3 eta is the product of the YWHAH gene, located on chromosome 22q12.3. It is about 13 kilobase long, consisting of two exons separated by a single intron. This gene has been implicated in linkage studies to bipolar disorder and schizophrenia. Six YWHAH single nucleotide polymorphisms (SNPs) were identified in a prior study: rs2246704, rs2853884, rs3747158, rs4820059, rs7291050, and rs933226. rs2246704 was associated with bipolar disorder (Odds Ratio (OR) 1.31, p=0.03) and psychotic BP (OR 1.66, p=0.002). All six SNPs are intronic. It was hypothesized that one or several of these 6 single nucleotide polymorphisms (SNPs) could be related to RA disease severity.

Study Timeline

• Study Start: 2015-06-01
• Status Verified: 2017-06
• Primary Completion: 2017-06-01
• Study Completion: 2017-06-01
• Study First Submitted: 2017-06-11
• Study First Submitted QC: 2017-06-14
• Last Update Submitted: 2017-06-14
• Study First Posted: 2017-06-19
• Last Update Posted: 2017-06-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 71

Inclusion Criteria

• Have RA per 1987 or 2010 American College of Rheumatology Classification Criteria

Exclusion Criteria

• None

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
No SNP	TaqMan SNP analysis	Subjects have two copies of the wild type gene
SNP present	TaqMan SNP analysis	Subjects have one or two copies of the SNP

Primary Outcome Measures

Name	Time	Method
Relationship to RA disease severity	2.5 years	The primary endpoint was the relationship of the six YWHAH SNPs to RA disease severity as based on the presence (1 point) or absence (0 points) across several domains: (A) serologic status (positive anti-CCP = 1 point, for example), (b) erosive changes (presence of erosions = 1 point), and (c) extra-articular manifestations (presence = 1 point).