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Objective: To determine (1) whether the A(-2518)G polymorphism of CCL-2, the gene encoding monocyte chemoattractant protein-1 (MCP-1), is associated with disease, MCP-1 concentration, nephritis, or coronary artery calcification (CAC) in systemic lupus erythematosus (SLE); and (2) whether MCP-1 and homocysteine (Hcy) concentrations are correlated., Methods: Statistical tests were applied to determine the relationships between CCL-2 A(-2518)G genotypes, plasma MCP-1 concentrations, and clinical variables in Caucasian and African American patients with SLE and controls., Results: The CCL-2 (-2518)G allele was not significantly associated with SLE in the whole study sample (p = 0.07). Among Caucasians, but not African Americans, G allele carriers had significantly increased risk of SLE (OR 4.2, 95% CI 1.8-9.6, p < 0.0001). Genotype was not associated with nephritis, CAC, or MCP-1 concentrations when all patients or all controls were considered; however, among recently diagnosed patients, G allele carriers had significantly higher MCP-1 concentrations than AA homozygotes (p = 0.02). SLE patients had higher MCP-1 concentrations than controls (p < 0.0001), African American patients had higher concentrations than Caucasian patients (p = 0.006), and patients with nephritis had higher concentrations than those without nephritis (p = 0.02). Although not associated with CAC, MCP-1 concentrations were significantly positively correlated with Hcy. CONCLUSION. CCL-2 A(-2518)G genotype is a significant risk factor for SLE among Caucasians but not African Americans, suggesting that genetically mandated differences in MCP-1 expression contribute to SLE etiology in the former. The positive correlation between MCP-1 and Hcy concentrations is consistent with the hypothesis that active inflammation and hyperhomocysteinemia are etiologically linked.

Objective: High expression of circulating vascular endothelial growth factor (VEGF) has been reported in patients with Henoch-Schönlein purpura (HSP). We investigated the role of -1154 G-->A (rs1570360) and -634 G-->C (rs2010963) VEGF gene functional variants in the susceptibility to HSP, to identify associations with severe systemic complications of HSP, in particular with renal complications., Methods: Fifty-seven patients from the Lugo region of Northwest Spain with primary cutaneous vasculitis classified as HSP according to proposed criteria were studied. All patients were required to have had at least 2 years' followup. Patients and ethnically matched controls (n = 226) were genotyped for the VEGF -1154 G-->A and -634 G-->C polymorphisms using real-time PCR technology based on TaqMan 5' allelic discrimination assay., Results: No significant differences in the allele or genotype frequencies for the 2 VEGF polymorphisms were observed between HSP patients and controls. However, the high VEGF producer VEGF -1154 G allele was increased in HSP patients with nephritis compared with healthy controls (p = 0.02, OR 2.13, 95% CI 1.11-4.08; pc = 0.04). Similarly, the high VEGF producer VEGF -634 C allele was increased in patients with nephritis compared to controls (p = 0.04, OR 1.66, 95% CI 1.01-2.73; pc = 0.08). The -1154G/-634C haplotype was associated with susceptibility to nephritis (p = 0.03, OR 1.71, 95% CI 1.01-2.89). A protective effect against nephritis was observed for the -1154A/-634G VEGF promoter haplotype (p = 0.02, OR 0.49, 95% CI 0.30-0.95)., Conclusion: Our results suggest a potential implication of the VEGF -1154 G-->A and -634 G-->C polymorphisms in the development of nephritis in patients with HSP.

Objective: To assess the contribution of 2 polymorphisms within the inducible nitric oxide (NOS2A) promoter region to the susceptibility to Henoch-Schönlein purpura (HSP), and to determine if implications exist with severe systemic complications of HSP, in particular with severe renal involvement and permanent renal dysfunction (renal sequelae)., Methods: Fifty-eight patients from Northwest Spain with primary cutaneous vasculitis classified as HSP were studied. All patients were required to have had at least 2 years' followup. Patients and ethnically matched controls (n=251) were genotyped by PCR based techniques for a multiallelic (CCTTT)n and for the biallelic TAAA repeat in the promoter region of the NOS2A gene., Results: HSP patients exhibited a significantly increased frequency of the NOS2A short (8-11) CCTTTn alleles (OR 1.64, 95% CI 1.09-2.47, p=0.017) and genotypes (OR 3.59, 95% CI 1.79-7.20, p=0.0002) compared to controls, particularly when patients with nephritis were compared with controls. However, when the NOS2A TAAA repeat polymorphism was assessed, no differences were found., Conclusion: Significant differences in the NOS2A promoter polymorphism allele and genotype frequency between HSP patients and controls suggest a potential role for this gene in the susceptibility to HSP and in the development of nephritis.

Objective: To assess the influence of the interleukin (IL)-1beta gene (-511 C/T) in the incidence of Henoch-Schönlein purpura (HSP) and determine its possible implication in severe systemic complications of HSP, in particular severe renal involvement and permanent renal dysfunction (renal sequelae)., Methods: Patients from Northwest Spain with primary cutaneous vasculitis classified as HSP according to proposed criteria were studied. All patients were required to have had at least 2 years' followup. Patients and ethnically matched controls were genotyped for IL-1beta gene (-511 C/T) polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)., Results: Forty-nine Caucasian patients (38 of them younger than 21 years) who fulfilled classification criteria for HSP and 148 controls were examined. No allele or genotype differences between the whole group of HSP and controls were observed. However, all 5 patients who developed severe nephropathy during the course of disease carried the rare T allele compared with only 16 of the remaining 44 patients (pcorr = 0.01). A significant association between carriage of the -511(IL-1beta) T allele and renal sequelae (pc = 0.02; OR: 3.6, 95% CI: 1.3-10.0) was also found., Conclusion: In unselected patients with cutaneous vasculitis who fulfill classification criteria for HSP, carriage of IL-1beta (-511) T allele appears to influence severity of renal involvement.

Objective: To assess the influence of interleukin-8 (IL-8), epithelial cell-derived neutrophil-activating peptide (ENA-78), and regulated upon activation normal T cell expressed and secreted (RANTES) gene polymorphisms in the susceptibility and clinical expression of patients fulfilling classification criteria for Henoch-Schönlein purpura (HSP)., Methods: Fifty patients (25 men) from Northwest Spain with primary cutaneous vasculitis classified as HSP according to proposed criteria were studied. All patients were required to have had at least 2 years' followup. Patients and ethnically matched controls were genotyped for IL-8, ENA-78, and RANTES gene polymorphisms., Results: No allele or genotype differences between patients fulfilling HSP classification criteria and controls were observed for any of the chemokines. However, a significantly increased frequency of allele A of the IL-8 gene polymorphism was found in patients with HSP who developed renal manifestations compared with patients without renal involvement (p = 0.02; pcorr = 0.036). Moreover, the genotype distribution in HSP patients with and without renal involvement showed statistically significant differences (p = 0.02)., Conclusion: In unselected patients with cutaneous vasculitis, carriage of IL-8 allele A influences the susceptibility to renal involvement.

Objective: To investigate the implications of the HLA-B locus in the susceptibility to Henoch-Schönlein purpura (HSP) and determine if there are associations with renal and gastrointestinal (GI) manifestations of the disease., Methods: A retrospective study was performed on an unselected population of patients with HSP from Northwest Spain. Forty-eight Caucasian patients (24 women), 11 of them older than 20 years, were studied. Patients and ethnically matched controls were HLA-B genotyped from DNA using molecular based methods., Results: When patients with HSP were compared with matched controls, no differences in HLA-B frequencies were observed. No HLA-B associations with GI manifestations were observed. In contrast, an increased frequency of HLA-B35 was observed in patients with renal manifestations (10 of 31) compared to those without (0 of 17). No significant distortions in frequency were seen for any other HLA-B alleles with HSP subgroups., Conclusion: Our results support a role of HLA-B35 in the susceptibility for nephritis in unselected patients with HSP.