Journal
GENES AND IMMUNITY
Volume 5, Issue 6, Pages 484-492Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.gene.6364119
Keywords
systemic lupus erythematosus; interleukin 10; polymorphism; haplotype
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Several lines of evidence suggest interleukin-10 gene (IL-10) is a candidate gene in susceptibility to systemic lupus erythematosus (SLE). We investigated the association of IL-10 promoter single-nucleotide polymorphisms (SNPs) (-3575T/A, -2849G/A, - 2763C/A, - 1082A/G, - 819T/C and - 592A/C) and microsatellites (IL10.R, IL10.G) with SLE in 554 Hong Kong Chinese patients and 708 ethnically matched controls. Six haplotypes (hts) were identified from the SNPs. The genotype distribution of the ht1 (T-C-A-T-A), which is associated with low IL-10 production, was different in patients and controls ( P = 0.009). The homozygous genotype of non-ht1 was significantly increased in patients ( P = 0.009, odds ratio ( OR) = 1.80, 95% CI: 1.15 - 2.82). The frequency of IL10.G4 of IL10.G was also significantly increased in patients ( P = 0.017, OR = 2.53, 95% CI: 1.18-5.40). We found that the homozygous non-ht1 combined with short allele ( CA repeat number less than or equal to21) of IL10.G has a dose-dependent effect on SLE susceptibility: non-ht1/non-ht1 with homozygous short allele showed a higher OR ( OR = 4.11, 95% CI: 1.27 - 13.2, P = 0.018) of association with SLE than the genotype of non-ht1/non-ht1 with heterozygous short/long allele ( OR = 2.98, 95% CI: 1.26 - 7.07, P = 0.013) and homozygous long allele ( OR = 1.05, 95% CI: 0.62 - 1.78, P = 0.848). The frequency of non-ht1 was significantly increased in patients with serositis ( P<0.0001, OR = 2.42, 95% CI: 1.55 - 3.80). In conclusion, the high expression promoter genotype is associated with SLE in Chinese.
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