title: Chemokine MCP1/CCL2 and RANTES/CCL5 gene polymorphisms influence Henoch-Schönlein purpura susceptibility and severity.
abstract: OBJECTIVE
  Henoch-Schönlein purpura (HSP) is the most common small vessel vasculitis in children. It is considered to be an IgA-containing immune complex-mediated disease. Chemokines are small secreted proteins that attract leukocytes during inflammation. Our aim was to determine the serum levels of chemokines and investigate the association of chemokine gene polymorphisms with childhood HSP.
  
  
  METHODS
  Serum levels of chemokines (interleukin-8/CXCL8, MCP-1/CCL2, RANTES/CCL5, MIG/CXCL9, and IP-10/CXCL10) were determined using cytometric beads arrays. We investigated the association of three single-nucleotide polymorphisms (SNPs) MCP1/CCL2 -2518C/T, RANTES/CCL5 -403C/T, and RANTES/CCL5 -28C/G with HSP in 85 HSP patients and 136 healthy controls.
  
  
  RESULTS
  Five serum chemokine levels were significantly elevated in patients with the acute stage of HSP compared to the normal controls (p < 0.05). MCP1/CCL2 -2518 TT genotype and T allele were associated with the risk for HSP with OR (95% CI) 3.32 (1.45-7.59) and 1.78 (1.20-2.64), respectively. The RANTES/CCL5 -28 GG genotype was associated with a significantly lower percentage of corticosteroid usage and lower corticosteroid accumulative dose in HSP patients. RANTES/CCL5 -403 TC and TT genotype were significantly associated with renal manifestations with an OR (95% CI) of 4.33 (1.44-12.99), adjusted for sex and age and the other two SNP genotypes.
  
  
  CONCLUSIONS
  Our results support the fact that chemokines play important roles in the pathogenesis of HSP. MCP1/CCL2 gene polymorphisms were associated with susceptibility for HSP. RANTES/CCL5 gene polymorphisms may be related to disease severity and HSP nephritis.
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan, ROC.
authors.forename: Hsin-Hui
authors.initials: HH
authors.lastname: Yu
authors.affiliation: Clinical Informatics and Medical Statistics Research Center, Chang Gung University, Tao-Yuan, Taiwan, ROC.
authors.forename: Pi-Hua
authors.initials: PH
authors.lastname: Liu
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan, ROC.
authors.forename: Yao-Hsu
authors.initials: YH
authors.lastname: Yang
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan, ROC.
authors.forename: Jyh-Hong
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan, ROC.
authors.forename: Li-Chieh
authors.initials: LC
authors.lastname: Wang
authors.affiliation: Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan, ROC; Genetic Epidemiology Core Laboratory, Research Center for Medical Excellence, National Taiwan University, Taipei, Taiwan, ROC.
authors.forename: Wei-J
authors.initials: WJ
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan, ROC; Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan, ROC. Electronic address: gicmbor@ntu.edu.tw.
authors.forename: Bor-Luen
authors.initials: BL
authors.lastname: Chiang
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000235:genetics*; D018946:Chemokine CCL5 / Q000235:genetics*; D018925:Chemokines / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D011695:IgA Vasculitis / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D012720:Severity of Illness Index; D013624:Taiwan; D062606:Tertiary Care Centers
chemical_list: C111835:CCL2 protein, human; C483024:CCL5 protein, human; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D018925:Chemokines
keywords: Henoch–Schönlein Purpura (HSP); MCP1/CCL2; RANTES/CCL5; chemokine; polymorphism