POS0137 FREQUENCIES OF WNT PATHWAY GENE VARIANTS ASSOCIATED WITH ANTI CARBAMYLATE PROTEIN IN EARLY RHEUMATOID ARTHRITIS

BackgroundIncreased bone resorption and impaired bone formation characterize the pathogenesis of rheumatoid arthritis (RA). Wnt/β-catenin pathway regulates osteoblast function. Since bone mineral density (BMD) and RA joint destruction are partially inherited, we studied the association of Dickkopf-1 (DKK-1), sclerostin (SOST), Kremen-1 and lipoprotein receptor-related protein-5 (LRP-5) genes single nucleotide polymorphisms (SNPs).ObjectivesTo establish the genotypic frequency of variants of the DKK-1 (rs1896368, rs1896367, rs1528873), SOST (rs6503475), Kremen-1 (rs132274) and LRP-5 (3736228) genes in patients with early RA (eRA) and first degree relative (FDR) with healthy controls (HC), and its association with autoimmunity profile.MethodsColombian individuals were matched by age and gender. Serological and clinical indices were measured. Variants associated with the Wnt pathway; DKK-1, SOST, LRP-5, and Kremen were analyzed using High Resolution Melting and confirmed by Sanger sequencing. A bivariate analysis was conducted in eRA and FDR. A logistic regression was performed.Results232 individuals were evaluated; 66 eRA patients, 50 FDR, and 116 HC. For eRA, 78.8% were female, with a median age 52 years (IQR: 38,8-56). Higher levels of CRP: 4,2 (IQR: 1,6-11,6), RF: 30,2 (IQR: 1,2-74,1), anti-CCP: 7,81 (IQR: 7,81-104,9) and anti-Carbamylate protein (CarP): 17,7 (IQR: 12,3-31,8) were observed.Among eRA, FDR, and HC genotypic frequencies are listed in Table 1, there were significant differences among DKK-1 rs1528873 GA and AA (p<001), Kremen GG and GA (p<0,001), and LRP5 GG and GA (p=0,038), and GG with AA (p=0,023). In haplotype analysis between eRA and HC for DKK-1 rs1896368 GA and LRP-5 AA (p=0,033) and for LRP5 GG and AA DKK-1 rs1528873 (p<0,001).Table 1.Population genotypic frequencieseRAFDRHCn(%)n(%)n(%)p value*DKK-1 rs189636727 (40,9)25 (50)57 (49,1)GG Native39 (59,1)25 (50)59 (50,9)0,528GA Homozygous4 (6,1)4 (8)8 (6,9)0,890AA Heterozygous23 (34,8)21 (42)49 (42,2)0,597DKK-1 rs189636859 (89,4)45 (90)98 (84,5)GG Native7 (10,6)5 (10)18 (15,5)0,543GA Homozygous30 (45,5)21 (42)54 (46,6)0,882AA Heterozygous29 (43,9)24 (48)44 (37,9)0,450DKK-1 rs152887325 (37,9)24 (48)59 (50,9)TT Native42 (62,1)26 (52)57 (49,1)0,233TG Homozygous24 (36,4)5 (10)6 (5,2)<0,001GG Heterozygous1 (1,5)19 (38)53 (45,7)<0,001SOST rs650347551 (77,3)35 (70)85 (73,3)GG Native15 (22,7)15 (30)31 (26,7)0,657GA Homozygous13 (19,7)9 (18)28 (25)0,580AA Heterozygous38 (57,6)26 (52)56 (48,3)0,488KREMEN rs13227462 (93,9)28 (56)102 (87,9)CC Native4 (6,1)22 (44)14 (12,1)<0,001CT Homozygous35 (53)6 (12)54 (46,5)<0,001TT Heterozygous27 (40,9)22 (44)48 (41,4)0,953LRP-5 rs373622823 (34,8)16 (32)22 (19)CC Native43 (65,2)34 (68)94 (81)0,038CT Homozygous3 (4,5)10 (20)3 (2,6)0,038TT Heterozygous20 (30,3)6 (12)19 (16,4)0,023In eRA SOST rs6503475 was associated with anti-CarP (AOR 3,4 [95%IC 1,1-10,8] p=0,037). LRP-5 with former smoking (AOR 8,6 [95%IC 2,0-36,4] p=0,004). Additionally, in patients with a combination of at least three SNPs with a lower frequency of anti-Carp peptide (AOR 0,09 [95%IC 0,012-0,608], p=0,014), meanwhile a combination of at least five SNPs with a higher frequency of anti-Carp (AOR 4,7 [95%IC 1,27-17,1] p=0,020) were observed. There were no differences in FDR group.ConclusionSignificant associations between Wnt pathway genes variants, haplotypes, and antibody profile could reinforce evidence to relation of high titters of anti-CarP with decreased BMD in eRA patients.AcknowledgementsHospital Militar Central - Universidad El BosquDisclosure of InterestsNone declared