ObjectivesPrevious genome-wide association study showed that GLDC/IL33 loci were associated with overall survival in patients with osteosarcoma (OS). We performed a replication study to explore whether variants of GLDC/IL33 are associated with the survival of OS patients and to further verify their functional role in the gene expression.MethodsA total of 216 patients with OS were enrolled. The overall survival time was calculated from the date of diagnosis till the date of last follow-up or mortality. Two SNPs were genotyped, including rs55933544 and rs74438701. OS specimens were obtained from 72 patients during surgery. The gene expression level of IL33 and GLDC was evaluated by qPCR. Patients were classified into two groups according to the 5-year overall survival (death/survival). The chi-square test was used to analyze difference of genotype frequency. The Student t-test was used to compare the gene expression level between different genotypes. Cumulative survival time was calculated by the Kaplan–Meier method and analyzed by the log-rank test.ResultsGenotype TT of rs55933544 was significantly associated with the event of death (0.176 vs. 0.061, p < 0.001). Patients with no risk allele T of rs55933544 showed a 5-year overall survival of 81.4% (110/141), which was significantly higher than an overall survival of 55.0% (29/54) for patients with one risk allele and 44.8% (12/21) for patients with two risk alleles (p < 0.01). Genotype TT of rs55933544 were indicative of remarkably lower expression of IL33 than genotype CC (0.00041 ± 0.00025 vs. 0.00065 ± 0.00031, p = 0.04). Patients with low IL33 expression presented remarkably worse survival as compared with the patients with high IL33 expression (p < .01)ConclusionsVariant rs55933544 was associated with the survival time of OS patients. IL33 may contribute to a poor prognosis of OS. Further investigation into the biological mechanisms by which IL33 influences the overall survival can shed light on the improvement of clinical outcome for OS patients.
Background: Although arthroscopic partial meniscectomy is a widely implemented surgical procedure, studies investigating the time to return to activity (RTA) are rare. Purpose: To explore which factors are associated with the RTA times after arthroscopic partial meniscectomy and to investigate whether those factors can also improve short-term patient-reported outcomes. Study Design: Case-control study; Level of evidence, 3. Methods: The authors reviewed the records of patients who underwent isolated partial meniscectomy in their institution from January 2017 to December 2019. Patient and injury characteristics were documented, and time to RTA was obtained via phone interview in January 2021. Pre- and postoperative outcomes were assessed with the Lysholm score and International Knee Documentation Committee (IKDC) score. The chi-square test and independent-samples t test were used to evaluate differences in outcome scores and time to RTA according to the patient and injury characteristics, and risk factors with a P value <.1 in the univariate analysis were used in the binary regression. Results: Included were 215 patients (87 men and 128 women; mean age, 33.7 years [range, 24-75 years]). Of these patients, 204 provided information on time to RTA (mean, 3.3 months). By 3 months postoperatively, 49.5% (101/204) of patients could perform activities without knee-related restriction; this improved to 69.6% (142/204) at 6 months and 90.2% (184/204) at 12 months. On multivariate logistic regression analysis, age (OR, 0.39; 95% CI, 0.21-1.19; P = .044) and injury duration (OR, 0.20; 95% CI, 0.19-1.07; P = .032) were significantly associated with the time to RTA. IKDC scores improved significantly from 41.2 preoperatively to 76.7 postoperatively, and in the multivariate logistic regression model, female sex (OR, 2.67; 95% CI, 1.10-6.47; P = .030), body mass index (BMI) ≥27 kg/m2 (OR, 2.96; 95% CI, 1.02-8.66; P = .047), and medial meniscal tear (OR, 0.20; 95% CI, 0.04-1.00; P = .050) were associated with inferior outcome scores. Conclusion: Patients aged 40 years and younger who underwent partial meniscectomy surgery within 6 months after a meniscal tear were more likely to have a shorter time to RTA, and female patients with obesity (BMI ≥27 kg/m2), especially those with medial meniscal tears, tended to have inferior clinical outcomes.
Objectives In two previously published genome-wide association studies, a cluster of variants of sperm-associated antigen16 (SPAG16) were reported to be associated with the radiological progression rate of ACPA-positive rheumatoid arthritis (RA) patients from North American and Southern European ancestry. In this study, we aimed to investigate whether the reported RA-risk loci in SPAG16 are associated with the disease in the Chinese population and to further validate the functional role of the susceptible locus in RA tissues. Methods A total of 500 ACPA-positive RA patients and 1000 age-matched healthy subjects were recruited. Two SNPs of SPAG16, including rs7607479 (C/T) and rs6435818 (A/C), were genotyped, and the genotyping data were compared with chi-square test. Gene expression analysis was performed in synovial tissues obtained from 40 RA patients and 30 non-RA controls surgically treated for bone fracture. The tissue expression of SPAG16 and matrix metalloproteinase 3 (MMP-3) was compared between the two groups by the Student’s t test. The relationship between serum indexes and mRNA expression of SPAG16 and MMP-3 were evaluated by Spearman’s correlation analysis. Result For rs7607479, the frequency of genotype TT was significantly higher in RA patients than in the controls (49.0% vs. 40.4%, p = 0.002). The RA patients were found to have significantly lower frequency of allele C than the controls (30.9% vs. 36.8%, p = 0.001). As for rs6435818, there was no significant difference of genotype or allele frequency between the two groups. The mRNA expression of MMP-3 was 1.63-fold higher in the RA patients than in the controls (p < 0.001). The expression of SPAG16 was comparable between the two groups (p = 0.43). The mRNA expression of MMP-3 was 1.39-fold higher in patients with genotype TT than in the patients with genotype CC (p = 0.006). The mRNA expression level of MMP-3 was significantly correlated with serum rheumatoid factor (r = 0.498, p < 0.001) and C-reactive protein (r = 0.272, p = 0.01), weakly correlated with erythrocyte sedimentation rate (r = 0.236, p = 0.09). Conclusions We validated a common genetic risk factor in ACPA-positive patients with RA, which is associated with the tissue production of MMP-3 and disease progression. Further functional analysis into the role of rs7607479 in MMP-3 expression can shed new light on the genetic architecture of ACPA-positive RA.
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