Molecular Biology Reports

, Volume 38, Issue 1, pp 379–385 | Cite as

Association of polymorphisms in the human IL-10 and IL-18 genes with rheumatoid arthritis

  • Binwu Ying
  • Yunying Shi
  • Xiaofu Pan
  • Xingbo Song
  • Zhunchun Huang
  • Qian Niu
  • Bei Cai
  • Lanlan Wang
Article

Abstract

The decrease of anti-inflammatory cytokine and increase of pro-inflammatory cytokine was observed in rheumatoid arthritis (RA). Interleukin-10 (IL-10), a potent anti-inflammatory cytokine, has been demonstrated to suppress joint swelling and deformation in RA animal model. Interleukin-18 (IL-18), a widely distributed pro-inflammatory cytokine, induces the production of IFN-γ, activate NK cells, and promote inflammation. Recent studies demonstrated that the serum IL-10 and IL-18 levels may be influenced by genetics and related to susceptibility to several autoimmune diseases. In the present study, using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) and DNA sequencing techniques, we analyzed the genotype and allele distributions of two single nucleotide polymorphisms (SNP) loci in the promoter region of IL-10 and IL-18 genes (IL-10-592 A/C and IL-18-607 A/C loci, respectively). Our results indicated that IL-10-592 allelic and genotypic frequencies were significantly different between the RA patients and normal subjects (P < 0.05). In addition, significant differences of IL-10-592 allelic and genotypic frequencies were also detected between the patients with or without anti-cyclic citrullinated peptide antibody (anti-CCP) (P < 0.05). In contrast, allelic and genotypic frequencies of IL-18-607 did not show significant difference between RA patients and normal subjects (P > 0.05) or between anti-CCP-positive and anti-CCP-negative RA patients (P > 0.05). Furthermore, ELISA detection of IL-10 and IL-18 serum levels revealed that the genotype of IL-10-592 was associated with IL-10 serum level (P < 0.05), but the genotype and allele frequency of IL-18-607 was not associated with IL-18 serum level (P > 0.05). Taken together, our findings provide new insight for the polymorphism of IL-10 gene in the pathogenesis of RA.

Keywords

IL-10 IL-18 Single nucleotide polymorphisms Rheumatoid arthritis 

Abbreviations

IL-10

Interleukin-10

IL-18

Interleukin-18

RA

Rheumatoid arthritis

SNP

Single nucleotide polymorphisms

Anti-CCP

Anti-cyclic citrullinated peptide antibody

ELISA

Enzyme-linked immunosorbent assay

Th1

T-helper 1

Th2

T-helper 2

Supplementary material

11033_2010_119_MOESM1_ESM.doc (28 kb)
Supplementary material 1 (DOC 27 kb)
11033_2010_119_MOESM2_ESM.ppt (936 kb)
Supplementary Fig. 1Reverse sequencing results of PCR products of IL-10-592 and IL-18-607 SNP loci. Representative results for genotypes AA (a), CC (b) and AC (c) for IL-10-592 (A) and IL-18-607 (B) SNP loci, respectively. Arrow indicates the SNP position in PCR products of IL-10 and IL-18 genes (PPT 935 kb)

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Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Binwu Ying
    • 1
  • Yunying Shi
    • 2
  • Xiaofu Pan
    • 1
  • Xingbo Song
    • 1
  • Zhunchun Huang
    • 1
  • Qian Niu
    • 1
  • Bei Cai
    • 1
  • Lanlan Wang
    • 1
  1. 1.Department of Laboratory Medicine, West China HospitalSichuan UniversityChengduPeople’s Republic of China
  2. 2.Department of Nephrology, West China HospitalSichuan UniversityChengduPeople’s Republic of China

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