Relationship of YWHAH Polymorphisms to Rheumatoid Arthritis Disease Severity

Study Overview
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Brief Summary
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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
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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.

Official Title
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Relationship of YWHAH Polymorphisms to Rheumatoid Arthritis Disease Severity

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Diagnostic Test: TaqMan SNP analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have RA per 1987 or 2010 American College of Rheumatology Classification Criteria Exclusion Criteria: None

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No SNP<br>Subjects have two copies of the wild type gene | Diagnostic Test: TaqMan SNP analysis<br>* TaqMan SNP analysis of the YWHAH gene<br>|
| SNP present<br>Subjects have one or two copies of the SNP | Diagnostic Test: TaqMan SNP analysis<br>* TaqMan SNP analysis of the YWHAH gene<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relationship to RA disease severity | 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). | 2.5 years |