Relationship of YWHAH Polymorphisms to Rheumatoid Arthritis Disease Severity

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.