AB0096 ANALYSIS OF THE GENE EXPRESSION OF URAT-1, ABCG2, GLUT-9, OCT3, IL1β, TLR4 AND ALPK1 IN MONONUCLEAR CELLS OF PATIENTS WITH INTER-CRITICAL GOUT
Authors: Natsuko Paniagua Díaz, Laura Sanchez Chapul, Carlos Aguilar Salinas, Alicia Ortega Mora, Ambar López Macay
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Gout is a common type of arthritis that has incresed in the world due to environmental and genetic factors that associate it with an altered metabolic state. In Mexico, overweight, obesisty, diabetes and metabolic syndrome have incresed in children and adult population, These alterations are associated with the development of gout in adults. The gout is characterized by an inflammatory chronic process caused by the deposition of monosodium urate crystals (CUMs) in the joints. The recognition of these crystals by macrophages and neutrophils in the joint activates innate immunity. However, high levels of uric acid (UA) in intercritical phase could activate the expression of urate transporters and inflammation genes in other cell types such as monocytes and peripheral blood lymphocytes. <h3>Objectives</h3> The aim of this project was to analyze the changes in gene expression of SLC22A12, SLC2A9, SLC22A3, ABCG2, ALPK1, IL1β, TLR4 in peripheral blood mononuclear cells (PBMC) of mexican patients with inter-critical gouty arthritis and controls without hyperuricemia (HU) comparing it with their metabolic profile. <h3>Methods</h3> The determination of the biochemical parameters was performed by a serum - blood chemical test for uric acid, glucose, triglycerides, cholesterol, HDL, LDL and creatinine. through the use of<b> U</b>niCel DxC 600, Synchron Clinical System. The total RNA of the PBMC cells was amplified by qRT-PCR using the GoTaq® 1-Step RT-qPCR System real kit (Promega) and the Qiagen Rotor Gene Q kit, using specific primers. The gene expression analysis were performed by the ΔCT and ΔΔCT method and using GAPDH as a reference gene to compare the expression of urate transporter genes and inflammatory genes in the study groups. The expression results were associated to clinical and biochemical parameters such as levels of uric acid, triglycerides, and weight. All statistical analyzes were performed with the SPSS program (IBM 22 version for Windows, SPSS, Inc., Chicago, IL, EU), using student's t-test or U Mann-Whitney test, for the normal and non-normal data, when p * &lt;0.05 or p &lt;* 0.01. <h3>Results</h3> In this study we compared 24 patients with inter-critical gout and 26 controls without HU. It was found that the expression of ABCG2 was higher in the patients and that the expression of OCT3 was higher in overweight people, regardless of whether they had gout or not compared with normal weigh people. The expression of ALPK1 was higher among patients and controls while the expression of TLR4 and IL1β was not different. The patients had a higher mean in the levels of UA, triglycerides, weight, age and hypertension, but lower HDL than the controls. <h3>Conclusion</h3> Patients with inter-critical gout maintain metabolic alterations associated with the metabolic syndrome although some of them are under treatment. They are also characterized by having overexpression of ABCG2 and ALPK1. These conditions could favor a new attack of gout. <h3>References</h3> [1] Dalbeth, N.; Merriman, T. R.; Stamp, L. K., Gout. Lancet2016, 388 (10055), 2039-2052. [2] Merriman, T. R., An update on the genetic architecture of hyperuricemia and gout. Arthritis research &amp; therapy2015, 17, 98 [3] Ko, A. M.; Tu, H. P.; Liu, T. T.; Chang, J. G.; Yuo, C. Y.; Chiang, S. L.; Chang, S. J.; Liu, Y. F.; Ko, A. M.; Lee, C. H.; Lee, C. P.; Chang, C. M.; Tsai, S. F.; Ko, Y. C., ALPK1 genetic regulation and risk in relation to gout. International journal of epidemiology2013, 42 (2), 466-74. <h3>Disclosure of Interests</h3> None declared