THU0390 GENETIC STUDY OF MEDICAL IMAGE PROGRESSION IN A CHINESE AS POPULATION FOR SIX MONTHS’ FOLLOW-UP
Authors: LIU JING, Qi Zhu, Weilin Pu, Dongyi He, Hejian Zou, Xiaodong Zhou, John D Reveille, Jiucun Wang
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Genetic factors accounts for about 90% pathogenesis of ankylosing spondylitis (AS), and may predict the disease progression. MRI is an important tool for evaluating disease progression and assessing treatment response in patients with AS. <h3>Objectives</h3> This study aims to define correlation between AS-associated genetic variations and MRI scores of AS patients in Chinese population. <h3>Methods</h3> A total of 62 AS patients treated with TNF blockers from Guanghua medical center (Shanghai, China) were recruited in this study. All of AS patients were evaluated for disease progression with MRI (SPARCC) [1-3]. Measures of inflammation (bone marrow edema (BME) of sacroiliac joints (SIJ) and spine) and structural damage (fat metaplasia, erosion, backfill and ankylosis of SIJ) were recorded at baseline and six months' follow-up. The changes of MRI scores were defined as the score of six months' follow-up minus that of baseline. All of patients were examined with whole exon sequencing for genetic polymorphisms. Logistic regression analysis was performed and genetic variants with p &lt; 1E-4 were considered as significant. <h3>Results</h3> The results showed that seven genetic variants significantly enriched in extracellular matrix pathways were associated with the changes of BME score of SIJ and spine. Four genetic variants regulating bone homeostasis, such as<i> ABCA4</i>, were significantly associated with the changes of fat metaplasia. Twelve variants were associated with the changes of erosion, one of which regulated expression of <i>FBF1</i> according to GTEx database (β/p-value = -5.0/1.1E-5). Mouse with <i>Fbf1</i> knockout showed abnormality in insulin metabolism and skeleton (MGI database). Genetic variants of the adipose related gene (<i>CTBP2</i>) and bone related genes (<i>RGMA, BMP8A</i>) were associated with the changes of backfill. In addition, genetic variants of <i>FAT4</i> was associated with the changes of ankylosis (β/p-value = 6.8/1.4E-8). Mutation of <i>FAT4</i> caused two bone related diseases and mouse with <i>Fat4</i> knockout showed severe abnormality of skeleton (MGI database). <h3>Conclusion</h3> Overall, the results suggested that the polymorphisms of genes involved in extracellular matrix were associated with BME, and genetic variants involved in adipose and bone metabolism were associated with structural damage in AS patients. <h3>References</h3> [1] Maksymowych WP, Inman RD, Salonen D, Dhillon SS, Krishnananthan R, Stone M, et al. Spondyloarthritis Research Consortium of Canada magnetic resonance imaging index for assessment of spinal inflammation in ankylosing spondylitis. Arthritis and rheumatism. 2005 Aug 15; 53(4):502-509. [2] Maksymowych WP, Inman RD, Salonen D, Dhillon SS, Williams M, Stone M, et al. Spondyloarthritis research Consortium of Canada magnetic resonance imaging index for assessment of sacroiliac joint inflammation in ankylosing spondylitis. Arthritis and rheumatism. 2005 Oct 15; 53(5):703-709. [3] Maksymowych WP, Wichuk S, Chiowchanwisawakit P, Lambert RG, Pedersen SJ. Development and preliminary validation of the spondyloarthritis research consortium of Canada magnetic resonance imaging sacroiliac joint structural score. The Journal of rheumatology. 2015 Jan; 42(1):79-86. <h3>Disclosure of Interests</h3> JING LIU: None declared, Qi Zhu: None declared, Weilin Pu: None declared, Dongyi He: None declared, Hejian Zou: None declared, Xiaodong Zhou: None declared, John D Reveille Grant/research support from: Janssen Research &amp; Development, LLC, Jiucun Wang: None declared