ABSTRACT
Objective To examine the plasma β-catenin and DKK1 levels in patients with rheumatoid arthritis (RA) and to explore their relationship with bone and joint damage in RA.Methods One hundred and thirteen patients with RA and 120 healthy individuals were recruited into this research.Bone mineral density (BMD) in the femur and lumbar spine were measured with dual-energy X-ray absorptiometry (DEXA).Radiographs for two hands were evaluated according to the Sharp's method.Serum levels of β-catenin and DKK1 in all patients with RA and healthy controls were detected by enzyme-linked immunosorbent assay (ELISA).The 2-tailed independent samples t test was used for measurement data.Chi-square test was used for the enumeration data.Correlation analysis,linear regression and Logistic regression analysis were used as appropriate statistical analysis.Results ① Significantly higher serum levels of DKK1 were observed in RA patients than that in healthy controls [(8±7) vs(6±4) μg/ml,t=2.552,P=0.012],while there was no sinnificant difference with regard to the levels of β-catenin between the two groups.② Compared to control groups,patients with RA had lower BMDs at femur and lumbar spine (P＜0.01).Furthermore,incidence of osteoporosis (OP) in RA (31.9％,36/113) was remarkablely higher than that in healthy subjects (15.0％,18/120) (x2=9.290,P=0.002).③ There were obvious discrepancies in age,swollen joint count (SJC),swollen joint count index (SJI),alkaline phosphatase (AKP),joint narrowing space score,joint erosion score,Sharp score between patients with osteoporosis and without osteoporosis (P＜0.05).④ In RA group,DKK1 level was posi-tively related with plasma erythrocyte sedimentation rates (ESR),28-jonit disease activity score (DAS28),AKP,joint narrowing space score (P＜0.05).Serum β-catenin level was associated with ESR,AKP in RA (P＜0.05).⑤ Multiple linear regression analysis indicated that in the RA group,disease duration (b=0.709,t=9.560,P＜0.01,95％CI:2.154-3.286),HAQ (b=0.151,t=2.052,P=0.043,95％CI:0.234-15.243),DKK1(b=0.286,t=2.057,P=0.043,95％CI:0.034-2.028)were the contributors for joint space narrow score(R2=0.580,F=24.745,P＜0.01).⑥ Multiple Logistic regression analysis showed that the Sharp score (OR=1.018,P＜0.01,95％CI:1.008-1.028) was the risk factor for the occurrence of osteoporosis at femur in RA,while age (OR=1.087,P=0.012,95％CI 1.019-1.159) was the risk factor for osteoporosis at lumbar spine.Conclusion Serum DKK1 levels in RA increase significantly,while there is no apparent alteration in plasma β-catenin.Serum DKK1 is correlated with disease activity and joint space narrow score.
ABSTRACT
Objective To investigate the relationship between single-nucleotide polymorphism (SNP)in receptor activator for nuclear factor-κB ligand (RANKL),osteoprotegerin (OPG) gene and rheumatoid arthritis (RA).Methods In our study,3 SNPs in the genes of OPG (2 SNP:rs2073618,rs3102735) and RANKL (1 SNP:rs2277438) by ligase detection reactions from 200 RA and 201 controls were examined.BMD values of different areas were assessed using dual-energy X-ray absorptiometry.Clinical and laboratory parameters were collected.Analysis of variance,t-test and x2 test were used for statistical analysis.Results No signi-ficant differences in the distribution of the alleles and genotypes were observed between case group and the control group (P＞0.05).The haplotype analysis for RANKL and OPG SNPs showed that the rs2073618/rs2277438/rs3102735 GGG haplotype could reduce the risk of RA (1.5％ vs 6.0％,P=0.008; OR 0.216;95％CI:0.081 to 0.575) and the GAG haplotype increased the risk of RA (14.5％ vs 8.4％,P=0.007; OR 1.862,95％CI:1.179 to 2.943).Patients with RANKL-rs2277438 AA or GG genotypes (n=6) had significantly higher BMD values compared to those with AG genotypes (n=39) at spine lumber 3 (1.05±0.22 vs 0.93±0.26,t=2.314,P=0.023),spine lumber 4 (1.06±0.24 vs 0.94±0.28,t=2.27,P=0.030),spine lumber 2-4 (1.04±0.21 vs 0.89±0.28,t=2.788,P=0.007).The tender joint counts (13±7 vs 10±6),tender joint index (19±11 vs 13±9),and VAS score (5.7±1.9 vs 4.8±1.8) differed significantly between patients with the OPG-rs2073618 CC or GG genotypes (n=60) and GC genotypes (n=40).Conclusion The rs2073618/rs2277438/rs3102735GGG haplotype may be protective against RA,while GAG haplotype may increase the susceptibility to RA.RANKL gene SNP rs2277438 may affect BMD value at spine lumber,and OPG gene SNP rs2073618 may influence the disease activity of RA patients.