POS0073 ASSOCIATION OF SAA1 GENE POLYMORPHISM -13T/C (RS12218) WITH CRYOPYRIN ASSOCIATED PERIODIC SYNDROMES (CAPS), BUT NOT FAMILIAL MEDITERRANEAN FEVER (FMF)
Authors: I. Guseva, E. Fedorov, S. Salugina, M. Krylov, E. Samarkina
Journal: Annals of the Rheumatic Diseases (2021)

Background: Autoinflammatory diseases (AIDs) are a group of rare, genetically determined diseases characterized by a periodic events of inflammation, fever, and clinical symptoms that mimic rheumatic pathology. Laboratory serological markers of AIDs are C reactive protein (CRP) and serum amyloid A (SAA) protein. Objectives: We investigated whether SAA1 gene polymorphism -13T/C (rs12218) may affect the susceptibility to pediatric FMF and CAPS patients (pts). We also evaluate whether this polymorphism can affect CRP and SAA protein levels. Methods: 26 FMF pts - 8 boys, 18 girls; age - M(SD) 7.37(5.32) years and 24 CAPS pts - 12 girls, 12 boys; age – 4.76(5.83) years, and 95 healthy individuals (controls) were included in this study. The diagnosis of FMF was based on Turkish paediatric criteria for the diagnosis of familial Mediterranean fever [1] and was confirmed by the detection of pathogenic mutations of the MEFV gene in the homozygous or compound-heterozygous states. The diagnose of CAPS was made on the basis of characteristic clinical signs and was confirmed by the detection of a pathogenic mutation in the NLRP3 gene. SAA1 gene polymorphism -13T/C was genotyped using allele-specific RT-PCR assay. SAA protein concentration was measured using nephelometry in FMF and CAPS pts. Results: Table 1 shows the genotypic and allelic frequencies of SSA1 gene in FMF, CAPS and controls. There were no significant differences between FMF pts and controls in the genotypic and allelic distributions of -13T/C gene polymorphism. The frequency of -13C allele was significantly higher in CAPS pts compared with controls (OR=2.03 [CI 1.02-4.03], p=0.03). Moreover, a statistically significant difference was revealed in the genotypic and allelic distributions between FMF and CAPS pts groups (p=0.047 and p=0.02 respectively). The CRP levels did not correlate with SAA1 - 13T/C polymorphism. The SAA protein concentration was associated with SAA1 gene polymorphism in FMF pts (p=0.036). Table 1. The distribution of genotypes and alleles of SAA1 gene polymorphism -13T/C in FMF, CAPS and control groups. Genotypes/Alleles FMF n=26 (%) CAPS n=24 (%) Controls n=95 (%) TT 12 (46,2) 4 (16,7) 39 (41,1) TC 12 (46,2) 14 (58,3) 42 (44,2) CC 2 (7,7) 6 (25,0) 14 (14,7) P (pts vs controls) &gt;0,05 &gt;0,08 T 24 (63,2) 21 (50,0) 80 (61,5) C 14 (36,8) 21 (50,0) 50 (38,5) P (pts vs controls) &gt;0,05 0.03 Conclusion: Our preliminary study in small groups of pediatric FMF and CAPS pts revealed that SAA1 gene polymorphism -13T/C (rs12218) is associated with susceptibility to CAPS, but not FMF. The influence of this polymorphism on SAA protein levels in FMF pts was also shown. Further investigations are required to clarify the role of SAA1 gene polymorphism -13T/C in susceptibility to FMF and CAPS in large studies in different ethnic and population groups. References: [1]Yalcinkaya F, Ozen S, Ozcakar ZB, et al. Rheumatology (Oxford). 2009,48(4): 395-8. doi: 10.1093/rheumatology/ken509. Disclosure of Interests: None declared.