ASSOCIATION OF ADAMTS12 POLYMORPHISMS WITH RHEUMATOID ARTHRITIS IN KOREAN POPULATION

Background: A disintegrin and metalloproteinase (ADAM) with thrombospondin type 1 motif, 12 (ADAMTS12) is a degradative enzyme that interacts with the degradable fragments of cartilage oligomeric matrix protein, which is a prominent noncollagenous matrix component in articular cartilage. ADAMTS12 has been observed in the cartilage, synovial fluid and serum of arthritis patients, and may play an important role in the pathogenesis of arthritis. Objectives: In this study, we investigated whether the genetic polymorphisms of ADAMTS12 are associated with rheumatoid arthritis (RA) in a Korean population. Methods: To observe the association between ADAMTS12 and RA, we genotyped three single nucleotide polymorphisms (SNPs) (rs1364044, intron C/T; rs10461703, intron C/T; rs25754, missense Thr1495Ile) of ADAMTS12 using a direct sequencing method in 303 RA patients and 495 control subjects. Multiple logistic regression models were performed to analyze the genetic data. SNPStats and SNPAnalyzer Pro programs were used to estimate odds ratios, 95% confidence intervals, and p values. Bonferroni's correction (p) was conducted to obtain a defined result. Results: Of the three SNPs, the genotype frequency of rs10461703 was associated with the development of RA (p=0.0024 in the co-dominant model; p=0.0009 in the dominant model; p=0.0006 in the log-additive model). The allele frequency of rs10461703 also showed a significant difference between RA and controls (p<0.0001). The C allele frequency of rs10461703 was lower in the RA group (36.6%) than in the control group (45.7%), whereas the T allele frequency of rs10461703 in the RA group (63.4%) was higher than that in the control group (54.3%). The other two SNPs (rs1364044 and rs25754) were not associated with the development of RA. However, we did not find any association between the three tested SNPs and RA patients according to clinical features including erythrocyte sedimentation rate, C-reactive protein level, rheumatoid factor (+ and -) and bone erosion (+ and -). Table 1. Genotype and allele frequencies of ADAMTS12 SNPs in RA and control subjects SNPGenotype/AlleleRAControlModelOR95% CIPP Freq.%Freq.%LCLUCL rs1364044C/C9833.218739.8Co-dominant 10.800.571.140.391.00 C/T14147.820443.4Co-dominant 20.780.501.23 T/T5619.07916.8Dominant0.800.581.110.170.51 Recessive0.880.591.320.541.00 Over-dominant0.870.641.190.401.00 Log-additive0.870.701.080.210.63 C33757.157861.5 T25342.936238.51.200.971.480.090.27 rs10461703T/T12241.514529.3Co-dominant 11.71.212.400.00080.0024 T/C12943.924850.1Co-dominant 22.141.363.37 C/C4314.610220.6Dominant1.821.322.500.00030.0009 Recessive1.571.052.370.0270.08 Over-dominant1.320.971.790.0750.23 Log-additive1.511.211.880.00020.0006 T37363.453854.3 C21536.645245.70.690.560.85<0.0001<0.0001 Conclusions: Our results suggest that ADAMTS12 may be a susceptibility gene for RA development in the Korean population. Disclosure of Interest: None DeclaredCitation: Annals of the Rheumatic Diseases, volume 71, supplement 3, year 2012, page 639Session: Genomics, genetics and epigenetics of rheumatic diseases (Abstracts accepted for publication )