Skip to main content
Journal cover image

Variants in CXCR4 associate with juvenile idiopathic arthritis susceptibility.

Publication ,  Journal Article
Finkel, TH; Li, J; Wei, Z; Wang, W; Zhang, H; Behrens, EM; Reuschel, EL; Limou, S; Wise, C; Punaro, M; Becker, ML; Munro, JE; Flatø, B ...
Published in: BMC Med Genet
March 22, 2016

BACKGROUND: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease among children, the etiology of which involves a strong genetic component, but much of the underlying genetic determinants still remain unknown. Our aim was to identify novel genetic variants that predispose to JIA. METHODS: We performed a genome-wide association study (GWAS) and replication in a total of 1166 JIA cases and 9500 unrelated controls of European ancestry. Correlation of SNP genotype and gene expression was investigated. Then we conducted targeted resequencing of a candidate locus, among a subset of 480 cases and 480 controls. SUM test was performed to evaluate the association of the identified rare functional variants. RESULTS: The CXCR4 locus on 2q22.1 was found to be significantly associated with JIA, peaking at SNP rs953387. However, this result is subjected to subpopulation stratification within the subjects of European ancestry. After adjusting for principal components, nominal significant association remained (p < 10(-4)). Because of its interesting known function in immune regulation, we carried out further analyses to assess its relationship with JIA. Expression of CXCR4 was correlated with CXCR4 rs953387 genotypes in lymphoblastoid cell lines (p = 0.014) and T-cells (p = 0.0054). In addition, rare non-synonymous and stop-gain sequence variants in CXCR4, putatively damaging for CXCR4 function, were significantly enriched in JIA cases (p = 0.015). CONCLUSION: Our results suggest the association of CXCR4 variants with JIA, implicating that this gene may be involved in the pathogenesis of autoimmune disease. However, because this locus is subjected to population stratification within the subjects of European ancestry, additional replication is still necessary for this locus to be considered a true risk locus for JIA. This cell-surface chemokine receptor has already been targeted in other diseases and may serve as a tractable therapeutic target for a specific subset of pediatric arthritis patients with additional replication and functional validation of the locus.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

BMC Med Genet

DOI

EISSN

1471-2350

Publication Date

March 22, 2016

Volume

17

Start / End Page

24

Location

England

Related Subject Headings

  • White People
  • Sequence Analysis, DNA
  • Receptors, CXCR4
  • Principal Component Analysis
  • Polymorphism, Single Nucleotide
  • Molecular Sequence Data
  • Male
  • Humans
  • Genotyping Techniques
  • Genome-Wide Association Study
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Finkel, T. H., Li, J., Wei, Z., Wang, W., Zhang, H., Behrens, E. M., … Hakonarson, H. (2016). Variants in CXCR4 associate with juvenile idiopathic arthritis susceptibility. BMC Med Genet, 17, 24. https://doi.org/10.1186/s12881-016-0285-3
Finkel, Terri H., Jin Li, Zhi Wei, Wei Wang, Haitao Zhang, Edward M. Behrens, Emma L. Reuschel, et al. “Variants in CXCR4 associate with juvenile idiopathic arthritis susceptibility.BMC Med Genet 17 (March 22, 2016): 24. https://doi.org/10.1186/s12881-016-0285-3.
Finkel TH, Li J, Wei Z, Wang W, Zhang H, Behrens EM, et al. Variants in CXCR4 associate with juvenile idiopathic arthritis susceptibility. BMC Med Genet. 2016 Mar 22;17:24.
Finkel, Terri H., et al. “Variants in CXCR4 associate with juvenile idiopathic arthritis susceptibility.BMC Med Genet, vol. 17, Mar. 2016, p. 24. Pubmed, doi:10.1186/s12881-016-0285-3.
Finkel TH, Li J, Wei Z, Wang W, Zhang H, Behrens EM, Reuschel EL, Limou S, Wise C, Punaro M, Becker ML, Munro JE, Flatø B, Førre Ø, Thompson SD, Langefeld CD, Glass DN, Glessner JT, Kim CE, Frackelton E, Shivers DK, Thomas KA, Chiavacci RM, Hou C, Xu K, Snyder J, Qiu H, Mentch F, Wang K, Winkler CA, Lie BA, Ellis JA, Hakonarson H. Variants in CXCR4 associate with juvenile idiopathic arthritis susceptibility. BMC Med Genet. 2016 Mar 22;17:24.
Journal cover image

Published In

BMC Med Genet

DOI

EISSN

1471-2350

Publication Date

March 22, 2016

Volume

17

Start / End Page

24

Location

England

Related Subject Headings

  • White People
  • Sequence Analysis, DNA
  • Receptors, CXCR4
  • Principal Component Analysis
  • Polymorphism, Single Nucleotide
  • Molecular Sequence Data
  • Male
  • Humans
  • Genotyping Techniques
  • Genome-Wide Association Study