The role of A268V exon-7 polymorphism of PPARA in development of axial spondyloarthritis; [Aksiyal spondiloartrit gelişiminde PPARA'nın A268V ekson-7 polimorfizminin rolü]

Objectives: Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that mainly affects the axial skeleton. Peroxisome proliferator activated receptor alpha (PPARA) is an intracellular transcription factor, which play a role in inflammation and osteoblasting activity. This study is designed to investigate the relationship of NG_012204.2:p.Ala268Val polymorphism of PPARA with axSpA risk and its role in disease development. Methods: This study was conducted with 168 patients and 181 controls. Genotyping was done with MALDITOF. Gene expression level was analyzed by quantitative real time PCR (RT-qPCR). The protein homology models of PPARA were created with ProMod3. Ligand binding dynamics were tested using the AutoDock4 docking program. Statistical evaluations were made with SPSS (ver24) and GeneGlobe. Results: Our results showed that C>T polymorphism causing NG_012204.2:p.Ala268Val change was associated with disease risk (p=0.024) and T allele increased disease risk 1.7 times (95% CI=1.070-2.594). PPARA expression decreased (p<0.05) in individuals carrying the T allele. We determined that the ligand entry pocket was opened 1.1 Å in the polymorphic PPARA. Polymorphic change caused a decrease in the ligand binding affinity. Conclusions: Our results provide an important contribution to elucidating the development of axSpA and demonstrate the potential of PPARA as a marker for the diagnosis of axSpA.