While genetic analyses have revealed ~100 risk loci associated with osteoarthritis (OA), only eight have been linked to hand OA. Besides, these studies were performed in predominantly European and Caucasian ancestries. Here, we conducted a genome-wide association study in the Han Chinese population to identify genetic variations associated with the disease. We recruited a total of 1136 individuals (n = 420 hand OA-affected; n = 716 unaffected control subjects) of Han Chinese ancestry. We carried out genotyping using Axiom Asia Precisi on Medicine Research Array, and we employed the RegulomeDB database and RoadMap DNase I Hypersensitivity Sites annotations to further narrow down our potential candidate variants. Genetic variants identified were tested in the Geisinger’s hand OA cohort selected from the Geisinger MyCode community health initiative (MyCode®). We also performed a luciferase reporter assay to confirm the potential impact of top candidate single-nucleotide polymorphisms (SNPs) on hand OA. We identified six associated SNPs (p-value = 6.76 × 10−7–7.31 × 10−6) clustered at 2p13.2 downstream of the CYP26B1 gene. The strongest association signal identified was rs883313 (p-value = 6.76 × 10−7, odds ratio (OR) = 1.76), followed by rs12713768 (p-value = 1.36 × 10−6, OR = 1.74), near or within the enhancer region closest to the CYP26B1 gene. Our findings showed that the major risk-conferring CC haplotype of SNPs rs12713768 and rs10208040 [strong linkage disequilibrium (LD); D’ = 1, r2 = 0.651] drives 18.9% of enhancer expression activity. Our findings highlight that the SNP rs12713768 is associated with susceptibility to and severity of hand OA in the Han Chinese population and that the suggested retinoic acid signaling pathway may play an important role in its pathogenesis.
Background/Purpose. To evaluate the relationship between the level of cytokines and the clinical findings in patients with ankylosing spondylitis (AS). Methods. The study enrolled 81 AS patients and 49 healthy adults. The serum levels of Interleukin (IL)-1β, IL-10, and tumor necrosis factor (TNF)-α were determined and compared between patients and control subjects. We also assessed the correlation between the production of cytokines and clinical parameters of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI). Results. Mean serum IL-1β level was significantly higher in AS patients than in control subjects (195.5±72.4 pg/mL vs 96.3±32.8 pg/mL; p＜0.001). Mean serum TNF-α level was also significantly higher in patients with AS than in controls (85.3±42.1 pg/mL vs 34.3±12.8 pg/mL; p=0.02). However, no significant differences were observed in levels of IL-10 between patients and controls. Furthermore, serum IL-1β and TNF-α levels in the AS patients positively correlated with the parameters in the BASDAI (p=0.007, r=0.32 and p=0.001, r=0.41, respectively). There was also a positive correlation between erythrocyte sedimentation rate and TNF-α (p=0.01; r=0.31). Conclusion. Patients with a high BASDAI have higher levels of circulating TNF-α and IL-1β than patients with a low BASDAI or healthy individuals, suggesting that proinflammatory cytokines may play an important role during active inflammation.
It is well known that patients with rheumatoid arthritis (RA) have osteopenia. The etiology and the mechanisms producing this bone loss are poorly understood. Osteocalcin (OC) is a marker for bone metabolism and reflects bone formation. We investigated in a one-year prospective study whether the serum OC concentrations in patients with RA was significantly changed with the variation of inflammatory activity, functional stages, or disease modifying antirheumatic drug (DMARD) treatments. Twenty-eight RA patients was enrolled in this prospective study. After a one-year treatment, we could demonstrate a statistical increase in OC values (1.48±0.96→2.18±1.88 ng/mL, p ＜0.05). However, no significant differences in serum OC concentrations in patients who showed a fall in erythrocyte sedimentation rate (ESR) (≧1SD: 39 mm/h) or C reactive protein (CRP) (≧1SD: 3.9 mg/dL) were observed. Likewise, OC values of patients without such changes of inflammatory activity (ESR or CRP＜1SD) did not increase. We found no correlation of ESR differences and CRP differences with OC differences. Our data suggested that OC levels, a useful follow-up variable of bone turnover, increased significantly after one year of DMARD treatment. This seemed, however, not to be associated with functional stages and inflammatory activity in patients with RA.
Tumor necrosis factor-alpha (TNF-α) inhibitors including etanercept have been demonstrated to be very effective in severe ankylosing spondylitis (AS) in Caucasian patients. However, clinical efficacy of etanercept to treat active AS in Chinese patients has not been reported. In this study, a prospective, open-label trial of etanercept (25 mg BIW), involving 46 AS patients from 16 medical centers of Taiwan, was conducted. Questionnaire was utilized to record demographic data and clinical parameters, including Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), Bath AS Global Index (BASGI), Assessment in Ankylosing Spondylitis (ASAS) 20, 50, and 70, and others, before and at different time intervals after etanercept treatment. Laboratory tests including blood chemistry, hematology, urine analysis, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were done at baseline and at weeks 4, 8, and 12. In this 12-week study, etanercept demonstrated rapid and significant improvement in the ASAS20 response criteria (91.3%), at as early as 2 weeks of therapy (71.3%). Partial remission of AS was achieved in 49.3% of patients after 12 weeks of treatment. Disease activity (BASDAI) and function (BASFI) were also significantly improved after 12 weeks etanercept treatment (p < 0.0001 and p < 0.0001, respectively). In addition, significant increase of chest expansion (2.77 ± 1.69 cm versus 3.56 ± 1.82 cm, p = 0.0004) and lumbar flexion (2.11 ± 2.76 cm versus 2.58 ± 3.42 cm, p = 0.0075) and significant reduction of occiput-to-wall distance (6.59 ± 7.14 cm versus 5.32 ± 6.65 cm, p = 0.0006) were also demonstrated. Both ESR and CRP declined significantly after patients were treated with etanercept. There were no severe adverse effects during the treatment period. Etanercept is generally safe, well tolerated, and effective in Chinese patients with severe AS. Clinical efficacy, including partial remission and BASDAI, is even better in Chinese than in Caucasian patients. Further study is required to assess long-term efficacy and safety in Chinese patients with AS.
To identify new genetic variants associated with SLE in Taiwan and establish polygenic risk score (PRS) models to improve the early diagnostic accuracy of SLE.
This study evaluated the antioxidant capacity of Ricinus communis L. (RC) leaves and powder when used as a feed additive for laying hens. Results showed that the total phenolic content of the aqueous leaf extract of Ricinus communis L. (RCE) was 48.39 mg gallic acid equivalent (GAE) per gram dry weight (DW). The flavonoid content was 9.76 mg quercetin dihydrate equivalent (QE)/g DW. Ferrous chelating activity was approximately 56.2% with an RCE concentration of 1 mg/mL; the highest chelating activity was 91.2% with 4 mg/mL extract. The reducing power of 1 mg/mL RC was 1.17 times better than 1 mg/mL butylated hydroxytoluene (BHT). The Trolox equivalent antioxidant capacity (TEAC) value of 12.5 mg/mL RCE was equivalent to 3.09 mg/mL Trolox. RCE (10 mg/mL) had a lipid oxidative inhibition capacity of 35.3%. A total of 80 ISA brown laying hens at twenty-nine weeks of age were randomly allocated into the control or 1 of 3 treatment groups; the latter received 0.5%, 1% or 2% of RC, respectively, for 12 weeks. Results showed that the RC supplementation improved the feed conversion rate and 0.5% RC generated the best results. Additionally, the egg yolk score was significantly increased in all RC-supplemented groups. Moreover, there was no significant difference in serum characteristics between the treatment groups. Serum antioxidant enzyme activity showed that superoxide dismutase (SOD) activity increased in the RC-supplemented groups relative to the control but was not significantly different. mRNA expression levels of the antioxidant regulatory genes GCLC, GST, HO-1, SOD1, and SOD2 were significantly increased with 2% RC supplementation. In summary, RC is a suitable feed additive for laying hens and the addition of 0.5% RC leaf powder resulted in the greatest benefits.
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