AB0401 ASSESSMENT OF GENES INVOLVED IN SJÖGREN’S SYNDROME RELATED XEROSTOMIA

Background:Sjögren’s syndrome (SS) is characterized by decreased saliva secretion. It is regulated mainly by parasympathetic nervous system. The genes involved in xerostomia can play a neuroprotective role [1]. The expression profiling is helpful to understand the mechanisms of SS related xerostomia.Objectives:We aimed to investigate and compare gene expression in labial salivary glands from SS patients with xerostomia SS(+) and without xerostomia SS(-) and healthy subjects (HS) by microarray analysis and to find genes potentially involved in xerostomia.Methods:The study group comprised 11 SS patients (3 SS(+) and 8 SS(-)) and 9 HS. Labial salivary gland samples were processed according to the protocol [2]. Database for Annotation, Visualization and Integrated Discovery (DAVID) and Search Tool for the Retrieval of Interacting Genes (STRING10) were used for the interactions between study groups [3].Results:Among the genes belonging to “secretion” ontology group, expression of Amyloid Beta Precursor Protein (APP) and Cholinergic Receptor Muscarinic 3 (CHRM3) in both SS(+) and SS(-) groups were lower than in HS. The expression of Visinin Like 1 (VSNL1) in SS(+) and SS(-) was higher than in HS. The expression of Serum Amyloid A1 (SAA1) and Amyloid Beta Precursor like Protein 2 (APLP2) were decreased in SS(+) group and increased in SS(-) compared to HS group. There was no differences between the SS(+) and SS(-) in expression of mentioned genes.Table 1.Fold changes, adjusted p values of differentially expressed genes in SS(+) and SS(-) groupsGene symbolRatio SS(-)Ratio SS(+)adjusted p.value.SS(-)adjusted p.value.SS(+)APP-1,230085-4,002010,98240560,00029089SAA11,446255611-2,2223292250,8318722320,046639694APLP21,118778-2,2326460,91213550,01132797CHRM3-1,745830276-5,3594315930,8679315750,000023VSNL11,6085048523,1275270260,9162289640,000513257Figure 1.STRING-generated interaction network among differentially expressed genes belonging to the „secretion” ontology group.Conclusion:Decreased expression of APP, SAA1, APLP2 and CHRM3 in SS(+) sufferers compared to HS can reflect the loss of their neuroprotective function and the cholinergic deficiency in xerostomia. STRING10 software indicates for a cenral role of APP and genes involved in β-amyloid peptide formation and neurodevelopment and for a close relationships between SS and neurodegenerative diseases [4,5].References:[1]Bhattarai KR, Junjappa R, Handigund M, et al. The imprint of salivary secretion in autoimmune disorders and related pathological conditions. Autoimmunity Reviews. 2018, 17:376-390[2]Celichowski P, Nawrocki MJ, Dyszkiewicz-Konwińska M, et al. „Positive regulation of RNA metabolic proces” ontology group highly regulated in porcine oocytes matured in vitro: a microarray approach. BioMed Research International 2018, ID2863068.[3]Von Mering C, Jensen LJ, Snel B. „STRING: known and predicted protein-protein associations, integrated and transffered across organisms” Nucleic Acids Research. 2005, 33, suplement 1, pp DD433-D437.[4]Montibeller L, de Belleroche J. Amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (AD) are characterised by differentia activation of ER stress pathways: Focus on UPR target genes. Cell Stress and Chaperones. 2018, 23:897-912.[5]Fisher A, Pittel Z, Haring R, et al. M1 Muscarinic Agonists can modulate some of the hallmarks in Alzheimer’s disease. J Molecular Neuroscience. 2003, 20:349-356.Disclosure of Interests:None declared