Association of ficolin-2 gene polymorphisms and susceptibility to systemic lupus erythematosus in Egyptian children and adolescents: a multicenter study.

BACKGROUND: Pediatric-onset SLE (pSLE) is a multisystem autoimmune disease. Recently, the ficolin-2 (FCN2) gene has emerged as a potential candidate gene for susceptibility to SLE. OBJECTIVES: The objective of this study was to evaluate the association of the FCN2 gene polymorphisms at positions -986 (G/A), -602 (G/A), -4 (A/G) and SNP C/T (rs3124954) located in intron 1, with susceptibility to pSLE in Egyptian children and adolescents. METHODS: This was a multicenter study of 280 patients diagnosed with pSLE, and 280 well-matched healthy controls. The FCN2 promoter polymorphisms at -986 G/A (rs3124952), -602 G/A (rs3124953), -4 A/G (rs17514136) and SNP C/T (rs3124954) located in intron 1 were genotyped by polymerase chain reaction, while serum ficolin-2 levels were assessed using enzyme-linked immunosorbent assay. RESULTS: The frequencies of the FCN2 GG genotype and G allele at -986 and -602 positions were significantly more represented in patients with pSLE than in controls (p < 0.001). Conversely, the FCN2 AA genotype and A allele at position -4 were more common in patients than in controls (p < 0.001). Moreover, patients carrying the FCN2 GG genotype in -986 position were more likely to develop lupus nephritis (odds ratio: 2.6 (95% confidence interval: 1.4-4.78); p = 0.006). The FCN2 AA genotype at position -4 was also identified as a possible risk factor for lupus nephritis (odds ratio: 3.12 (95% confidence interval: 1.25-7.84); p = 0.024). CONCLUSION: The FCN2 promoter polymorphisms may contribute to susceptibility to pSLE in Egyptian children and adolescents. Moreover, the FCN2 GG genotype at position -986 and AA genotype at position -4 were associated with low serum ficolin-2 levels and may constitute risk factors for lupus nephritis in pSLE.

Increased bcl-2 expression is associated with primary resistance to chemotherapy in human epithelial ovarian cancer.

OBJECTIVE: bcl-2, an anti-apoptotic factor, has a role in the pathogenesis of ovarian cancer as well as in resistance to chemotherapy. DESIGN AND METHODS: 20 benign, and 26 malignant epithelial ovarian tissues were analyzed for bcl-2 protein and mutant p53 by enzyme-immunoassay (EIA). Flowcytometric analysis was also performed. Patients of malignant group were followed up to monitor overall survival and primary resistance to chemotherapy. RESULTS: bcl-2 was significantly higher in malignant group than benign group (p < 0.001). A cutoff value was determined for bcl-2 (63.8 kU/g protein). At this cutoff, sensitivity is 80.7%, and specificity is 85%. Using chi square analysis, a significant correlation was found between bcl-2 and FIGO stage (p = 0.01), overall survival (p = 0.01), as well as primary resistance to chemotherapy (p = 0.03). By correlation coefficient analysis the relation between bcl-2 and synthetic phase fraction was highly significant (p = 0.002). Bcl-2, p53, and FIGO stage were significantly correlated to poor survival (p = 0.01) in univariate analysis. However, in multivariate analysis, only FIGO stage, and p53 were independent risk factors. CONCLUSION: EIA could be a useful tool for investigating the prognostic value of bcl-2, and its possible prediction of platinum resistance in epithelial ovarian cancer. This might help in selecting patients for future anti-bcl-2 therapy.