1.Circulating VEGF levels and genetic polymorphisms in Behçet’s disease: a meta-analysis
Journal of Rheumatic Diseases 2025;32(2):122-129
Objective:
This study aimed to explore the relationship between circulating vascular endothelial growth factor (VEGF) levels and Behçet’s disease (BD), as well as to examine the association between VEGF gene polymorphisms and BD.
Methods:
We conducted a comprehensive search of the MEDLINE, Embase, and Web of Science databases to identify relevant research articles. A meta-analysis was performed to compare serum or plasma VEGF levels in BD patients with those in control groups. Additionally, we evaluated the potential associations between BD susceptibility and specific VEGF polymorphisms, namely –634 C/G, +936 C/T, and the 18 bp insertion/deletion (I/D) at –2549.
Results:
The analysis included 15 studies with a total of 1,020 BD patients and 1,031 controls. BD patients exhibited significantly higher circulating VEGF levels compared to controls (standardized mean difference [SMD]=1.726, 95% confidence interval [CI]=1.030~2.421, p<0.001). Elevated VEGF levels were noted among BD patients from European and Arab populations. Subgroup analysis further confirmed the increase in VEGF levels across different data types and sample sizes. Patients with active BD had higher VEGF levels than those with inactive BD (SMD=0.635, 95% CI=0.092~1.177, p=0.022). However, no significant association was found between BD and the VEGF –634 C allele (odds ratio=1.023, 95% CI=0.707~1.481, p=0.904). Similarly, no association was detected between BD and the VEGF +936 C/T or 18 bp I/D at –2549 polymorphisms.
Conclusion
Our meta-analysis showed a strong association between elevated circulating VEGF levels and BD. However, the VEGF polymorphisms examined in this study do not appear to be associated with susceptibility to BD.
3.Associations between circulating interleukin-18 levels and adult-onset Still’s disease: a meta-analysis
Journal of Rheumatic Diseases 2025;32(1):48-56
Objective:
This study aimed to investigate the link between circulating interleukin-18 (IL-18) levels and adult-onset Still’s disease (AOSD).
Methods:
A thorough search was performed on MEDLINE, Embase, and Web of Science to find relevant articles. A meta-analysis was conducted to compare serum/plasma IL-18 levels in AOSD patients to those in control subjects.
Results:
The meta-analysis included 13 studies with a total of 562 AOSD patients and 790 controls. The results showed a significant increase in IL-18 levels in the AOSD group compared to the control group (standard mean difference [SMD]=1.899, 95% confidence interval [CI]=1.078~2.720, p<0.001). When stratified by ethnicity, higher IL-18 levels were found in both Asian and European populations with AOSD. Subgroup analysis, regardless of variable adjustments, consistently indicated significantly higher IL-18 levels in the AOSD group. Significant elevations in IL-18 levels were observed in both small (n<50) and large groups (n>50), as well as in original and imputed data groups after data type stratification. Free IL-18 levels were significantly higher in the active group compared to the inactive group (SMD=0.900, 95% CI=0.532~1.268, p<0.001). The meta-analysis showed a positive correlation between IL-18 levels and ferritin (correlation coefficient=0.542, 95% CI=0.431~0.637, p<0.001) and C-reactive protein.
Conclusion
This meta-analysis demonstrated a significant increase in circulating IL-18 levels and a positive correlation between IL-18 levels and ferritin and C-reactive protein levels in patients with AOSD.
4.Circulating VEGF levels and genetic polymorphisms in Behçet’s disease: a meta-analysis
Journal of Rheumatic Diseases 2025;32(2):122-129
Objective:
This study aimed to explore the relationship between circulating vascular endothelial growth factor (VEGF) levels and Behçet’s disease (BD), as well as to examine the association between VEGF gene polymorphisms and BD.
Methods:
We conducted a comprehensive search of the MEDLINE, Embase, and Web of Science databases to identify relevant research articles. A meta-analysis was performed to compare serum or plasma VEGF levels in BD patients with those in control groups. Additionally, we evaluated the potential associations between BD susceptibility and specific VEGF polymorphisms, namely –634 C/G, +936 C/T, and the 18 bp insertion/deletion (I/D) at –2549.
Results:
The analysis included 15 studies with a total of 1,020 BD patients and 1,031 controls. BD patients exhibited significantly higher circulating VEGF levels compared to controls (standardized mean difference [SMD]=1.726, 95% confidence interval [CI]=1.030~2.421, p<0.001). Elevated VEGF levels were noted among BD patients from European and Arab populations. Subgroup analysis further confirmed the increase in VEGF levels across different data types and sample sizes. Patients with active BD had higher VEGF levels than those with inactive BD (SMD=0.635, 95% CI=0.092~1.177, p=0.022). However, no significant association was found between BD and the VEGF –634 C allele (odds ratio=1.023, 95% CI=0.707~1.481, p=0.904). Similarly, no association was detected between BD and the VEGF +936 C/T or 18 bp I/D at –2549 polymorphisms.
Conclusion
Our meta-analysis showed a strong association between elevated circulating VEGF levels and BD. However, the VEGF polymorphisms examined in this study do not appear to be associated with susceptibility to BD.
6.Associations between circulating interleukin-18 levels and adult-onset Still’s disease: a meta-analysis
Journal of Rheumatic Diseases 2025;32(1):48-56
Objective:
This study aimed to investigate the link between circulating interleukin-18 (IL-18) levels and adult-onset Still’s disease (AOSD).
Methods:
A thorough search was performed on MEDLINE, Embase, and Web of Science to find relevant articles. A meta-analysis was conducted to compare serum/plasma IL-18 levels in AOSD patients to those in control subjects.
Results:
The meta-analysis included 13 studies with a total of 562 AOSD patients and 790 controls. The results showed a significant increase in IL-18 levels in the AOSD group compared to the control group (standard mean difference [SMD]=1.899, 95% confidence interval [CI]=1.078~2.720, p<0.001). When stratified by ethnicity, higher IL-18 levels were found in both Asian and European populations with AOSD. Subgroup analysis, regardless of variable adjustments, consistently indicated significantly higher IL-18 levels in the AOSD group. Significant elevations in IL-18 levels were observed in both small (n<50) and large groups (n>50), as well as in original and imputed data groups after data type stratification. Free IL-18 levels were significantly higher in the active group compared to the inactive group (SMD=0.900, 95% CI=0.532~1.268, p<0.001). The meta-analysis showed a positive correlation between IL-18 levels and ferritin (correlation coefficient=0.542, 95% CI=0.431~0.637, p<0.001) and C-reactive protein.
Conclusion
This meta-analysis demonstrated a significant increase in circulating IL-18 levels and a positive correlation between IL-18 levels and ferritin and C-reactive protein levels in patients with AOSD.
7.Circulating VEGF levels and genetic polymorphisms in Behçet’s disease: a meta-analysis
Journal of Rheumatic Diseases 2025;32(2):122-129
Objective:
This study aimed to explore the relationship between circulating vascular endothelial growth factor (VEGF) levels and Behçet’s disease (BD), as well as to examine the association between VEGF gene polymorphisms and BD.
Methods:
We conducted a comprehensive search of the MEDLINE, Embase, and Web of Science databases to identify relevant research articles. A meta-analysis was performed to compare serum or plasma VEGF levels in BD patients with those in control groups. Additionally, we evaluated the potential associations between BD susceptibility and specific VEGF polymorphisms, namely –634 C/G, +936 C/T, and the 18 bp insertion/deletion (I/D) at –2549.
Results:
The analysis included 15 studies with a total of 1,020 BD patients and 1,031 controls. BD patients exhibited significantly higher circulating VEGF levels compared to controls (standardized mean difference [SMD]=1.726, 95% confidence interval [CI]=1.030~2.421, p<0.001). Elevated VEGF levels were noted among BD patients from European and Arab populations. Subgroup analysis further confirmed the increase in VEGF levels across different data types and sample sizes. Patients with active BD had higher VEGF levels than those with inactive BD (SMD=0.635, 95% CI=0.092~1.177, p=0.022). However, no significant association was found between BD and the VEGF –634 C allele (odds ratio=1.023, 95% CI=0.707~1.481, p=0.904). Similarly, no association was detected between BD and the VEGF +936 C/T or 18 bp I/D at –2549 polymorphisms.
Conclusion
Our meta-analysis showed a strong association between elevated circulating VEGF levels and BD. However, the VEGF polymorphisms examined in this study do not appear to be associated with susceptibility to BD.
9.Associations between circulating interleukin-18 levels and adult-onset Still’s disease: a meta-analysis
Journal of Rheumatic Diseases 2025;32(1):48-56
Objective:
This study aimed to investigate the link between circulating interleukin-18 (IL-18) levels and adult-onset Still’s disease (AOSD).
Methods:
A thorough search was performed on MEDLINE, Embase, and Web of Science to find relevant articles. A meta-analysis was conducted to compare serum/plasma IL-18 levels in AOSD patients to those in control subjects.
Results:
The meta-analysis included 13 studies with a total of 562 AOSD patients and 790 controls. The results showed a significant increase in IL-18 levels in the AOSD group compared to the control group (standard mean difference [SMD]=1.899, 95% confidence interval [CI]=1.078~2.720, p<0.001). When stratified by ethnicity, higher IL-18 levels were found in both Asian and European populations with AOSD. Subgroup analysis, regardless of variable adjustments, consistently indicated significantly higher IL-18 levels in the AOSD group. Significant elevations in IL-18 levels were observed in both small (n<50) and large groups (n>50), as well as in original and imputed data groups after data type stratification. Free IL-18 levels were significantly higher in the active group compared to the inactive group (SMD=0.900, 95% CI=0.532~1.268, p<0.001). The meta-analysis showed a positive correlation between IL-18 levels and ferritin (correlation coefficient=0.542, 95% CI=0.431~0.637, p<0.001) and C-reactive protein.
Conclusion
This meta-analysis demonstrated a significant increase in circulating IL-18 levels and a positive correlation between IL-18 levels and ferritin and C-reactive protein levels in patients with AOSD.
10.Circulating leptin and its correlation with rheumatoid arthritis activity: a meta-analysis
Journal of Rheumatic Diseases 2023;30(2):116-125
Objective:
The aim of the study was to investigate the association between the levels of leptin in the circulating of individuals with rheumatoid arthritis (RA) and the severity of the disease.
Methods:
We looked through the databases of Embase, Medline, and the Cochrane Library. We conducted a meta-analysis on the correlations between circulating leptin and the Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) and Creactive protein (CRP) levels in RA patients, as well as a meta-analysis of circulating or circulating leptin levels in RA patients.
Results:
This meta-analysis study analyzed 42 different comparisons from 37 different publications, including a total of 2,350 patients with RA and 1,815 controls. The RA group had substantially higher leptin levels than the control group (standardized mean difference [SMD]=0.507, 95% confidence interval [CI]=0.309~0.704, p<0.001). The finding that RA patients had higher leptin levels was unaffected by sample size. The correlation between circulating leptin levels and DAS28 is statistically significant (correlation coefficient=0.247, 95% CI=0.087~0.396, p=0.003). Leptin levels are also correlated with CRP levels (correlation coefficient=0.203, 95% CI=0.048~0.349, p=0.010).
Conclusion
This comprehensive meta-analysis demonstrates that the circulating leptin levels of RA patients are elevated, and provides compelling evidence of the significant relationship between leptin levels and the activity of RA. The findings of this research suggest that leptin plays a significant role in the pathophysiology of this disease.

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