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

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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.

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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

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Acknowledgements

We thank Dr. Junping Xin (Loyola University Medical Center) for critical review and editorial assistance during manuscript preparation. This study was supported by Grants from National Natural Science Foundation of China (#30900658) and from Sichuan University Young Scientist Funds (#2008095).

Conflict of interest statement

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, People’s Republic of China

    Binwu Ying, Xiaofu Pan, Xingbo Song, Zhunchun Huang, Qian Niu, Bei Cai & Lanlan Wang

  2. Department of Nephrology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China

    Yunying Shi

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  1. Binwu Ying
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Correspondence to Lanlan Wang.

Additional information

Binwu Ying, Yunying Shi and Xiaofu Pan have contributed equally to this work.

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Supplementary material 1 (DOC 27 kb)

Supplementary Fig. 1

Reverse 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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Ying, B., Shi, Y., Pan, X. et al. Association of polymorphisms in the human IL-10 and IL-18 genes with rheumatoid arthritis. Mol Biol Rep 38, 379–385 (2011). https://doi.org/10.1007/s11033-010-0119-x

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