SAT0218 SINGLE NUCLEOTIDE POLYMORPHISMS LOCATED IN REGULATORY REGIONS OF GENES INVOLVED IN SYSTEMIC INFLAMMATION (MAMDC1, ITGAM, AND CRP) CORRELATION WITH THE CLINICAL PICTURE OF DISEASE AND ACTIVITY PARAMETERS IN SYSTEMIC LUPUS ERYTHEMATOSUS
Authors: A. Majdan, R. Mlak, M. Mazurek, D. Pigon, M. Majdan, T. Malecka Massalska
Journal: Annals of the Rheumatic Diseases (2020)

Background: The exact pathogenesis of systemic lupus erythematosus (SLE) is poorly understood. It is an autoimmune disease that leads to a chronic inflammatory process involving numerous tissues and organs (skin, kidneys, joints, central nervous system, cardiovascular, respiratory, digestive and hematopoietic systems). However, despite the advancement of SLE molecular biology and the wide availability of tests and diagnostic tools, the knowledge about factors predicting the clinical disease activity as well as related changes in the laboratory results is insufficient. Objectives: The goal of the study was to assess the relationship between selected single nucleotide polymorphisms (SNPs) and the clinical picture of disease and some activity parameters in patients with SLE. Methods: We conducted a study of adult patients with SLE diagnosed and treated in the Rheumatology Department of Medical University of Lublin between 2016-2019. We enrolled 80 patients with SLE (71 women, 9 men), with the median (range) age 36 (19-72) and disease duration 6 (1-37) years. To objectively assess disease activity, standardized SLE activity scale - SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) was used. Using the Real-Time PCR method and specific TaqMan probes SNPs of 3 genes: MAMDC1 (rs910875; c.-1687G&gt; C), CRP (rs3091244; c.-390C&gt; A), and ITGAM (rs7193943; c.-323G&gt; A) were analyzed and then their relationship with specific clinical picture of disease, activity and laboratory results were assessed. Results: Carriers of the CC genotype compared to the remaining polymorphic variants (CG and GG) of the MAMDC1 gene had an approximately 4-fold higher risk of skin disease compared to other clinical pictures of disease (renal, articular, neuro-psychiatric, hematological) (OR = 4.04; p = 0.0110)). Carriers of this genotype also had a higher risk of hematuria (OR = 4.57; p = 0.0082), sterile leukocyturia (OR = 53.91; p = 0.0071), the presence of anti-Sm / RNP antinuclear antibodies (OR = 4.15, p = 0.0074), reduced values of the C3 complement component (OR = 6.11; p = 0.0071) and the need for oral glucocorticosteroids (OR = 7.01; p = 0.0028). In addition, significantly higher values of SLEDAI disease activity scale were observed in carriers of the CC genotype of the MAMDC1 gene (medians: 6 vs 4; p = 0.0220). Moreover, we observed a trend towards a higher risk of hepatomegaly in GG genotype carriers of the ITGAM gene (OR=18.50; p=0.0525). In addition, the AA genotype of the CRP gene was associated with a higher risk of proteinuria (OR = 84; p &lt;0.0001), Anti-SSA / Ro autoantibodies (OR = 3.29; p = 0.0484), and aCL IgM (OR = 3.42; p = 0.0332) occurrence. Carriers of AA genotype of the above gene were also at higher risk of earlier occurrence of first disease symptoms as well as disease diagnosis at a younger age (respectively: 24 vs 31 years; p=0.0225, 23 vs 29 years; 0.0442). Conclusion: The results suggest the relationship between SNPs in genes involved in systemic inflammation ( MAMDC1, ITGAM, CRP ) and disease activity as well as the occurrence of some specific clinical pictures of disease in patients with SLE.The genetic dispositions described above may serve as attractive markers in SLE, potentially useful in clinical practice. Disclosure of Interests: Aleksandra Majdan: None declared, Radosław Mlak: None declared, Marcin Mazurek: None declared, Dominika Pigon: None declared, Maria Majdan Consultant of: Roche, Amgen, Speakers bureau: Roche, Amgen, Teresa Malecka Massalska: None declared