Association of polymorphisms in the human IL-10 and IL-18 genes with rheumatoid arthritis.
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.
Ying
Binwu
B
Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, People's Republic of China.
Shi
Yunying
Y
Pan
Xiaofu
X
Song
Xingbo
X
Huang
Zhunchun
Z
Niu
Qian
Q
Cai
Bei
B
Wang
Lanlan
L
D000328:Adult; D000906:Antibodies / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D056426:Genetic Loci / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics*; D020382:Interleukin-18 / Q000097:blood / Q000235:genetics*; D008297:Male; D010456:Peptides, Cyclic / Q000276:immunology; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017186:Titrimetry
D000906:Antibodies; C508609:IL10 protein, human; D020382:Interleukin-18; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D016753:Interleukin-10