Chemokine MCP1/CCL2 and RANTES/CCL5 gene polymorphisms influence Henoch-Schönlein purpura susceptibility and severity

Hsin-Hui Yu; Pi-Hua Liu; Yao-Hsu Yang; Jyh-Hong Lee; Li-Chieh Wang; Wei-J Chen; Bor-Luen Chiang

doi:10.1016/j.jfma.2012.12.007

Chemokine MCP1/CCL2 and RANTES/CCL5 gene polymorphisms influence Henoch-Schönlein purpura susceptibility and severity

J Formos Med Assoc. 2015 Apr;114(4):347-52. doi: 10.1016/j.jfma.2012.12.007. Epub 2013 Feb 1.

Authors

Hsin-Hui Yu¹, Pi-Hua Liu², Yao-Hsu Yang¹, Jyh-Hong Lee¹, Li-Chieh Wang¹, Wei-J Chen³, Bor-Luen Chiang⁴

Affiliations

¹ Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan, ROC.
² Clinical Informatics and Medical Statistics Research Center, Chang Gung University, Tao-Yuan, Taiwan, ROC.
³ 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.
⁴ 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.

PMID: 25839768
DOI: 10.1016/j.jfma.2012.12.007

Abstract

Background/purpose: 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.

Conclusion: 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.

Keywords: Henoch–Schönlein Purpura (HSP); MCP1/CCL2; RANTES/CCL5; chemokine; polymorphism.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Case-Control Studies
Chemokine CCL2 / genetics*
Chemokine CCL5 / genetics*
Chemokines / blood
Child
Child, Preschool
Female
Genetic Predisposition to Disease
Humans
IgA Vasculitis / genetics*
Logistic Models
Male
Multivariate Analysis
Polymorphism, Single Nucleotide*
Severity of Illness Index
Taiwan
Tertiary Care Centers

Substances

CCL2 protein, human
CCL5 protein, human
Chemokine CCL2
Chemokine CCL5
Chemokines