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加那利群岛系统性红斑狼疮患者白细胞介素-10启动子多态性

Interleukin-10 promoter polymorphisms in patients with systemic lupus erythematosus from the Canary Islands.

作者信息

Rosado S, Rua-Figueroa I, Vargas J A, Garcia-Laorden M I, Losada-Fernandez I, Martin-Donaire T, Perez-Chacon G, Rodriguez-Gallego C, Naranjo-Hernandez A, Ojeda-Bruno S, Citores M J, Perez-Aciego P

机构信息

Fundacion LAIR, Madrid, Spain, and Sevicio de Medicina Interna I, Hospital Universitario Puerta de Hierro, Madrid, Spain.

出版信息

Int J Immunogenet. 2008 Jun;35(3):235-42. doi: 10.1111/j.1744-313X.2008.00762.x. Epub 2008 Apr 7.

Abstract

The purpose of this study was to examine whether several allelic variants in the polymorphic interleukin (IL)-10 promoter region were related with an increased risk of developing systemic lupus erythematosus (SLE) in Spanish patients from Canary Islands. Microsatellites (MS) at positions -4000 and -1200 (IL10R and IL10G, respectively) and single nucleotide polymorphisms (SNPs) (MS) at positions -1082G/A, -819C/T and -592C/A of the IL-10 promoter were analysed in patients with SLE and healthy controls from Canary Islands (Spain). We found that SNPs but not MS were associated with SLE. The GCC haplotype frequency was significantly higher in SLE patients (0.43) than in healthy donors (0.33) [P = 0.02; OR = 1.50 (95% CI = 1.06-2.14)], whereas the ACC haplotype was less represented in patients (0.28 vs. 0.37) [P = 0.02; OR = 0.64 (95% CI = 0.44-0.92)]. To assess the functional role of genotypes, serum IL-10 levels from patients and controls were quantified by ELISA. Also, the lipopolysaccharide-induced IL-10 secretion by monocytes from healthy controls was evaluated in vitro. Serum IL-10 levels were higher in patients [median (interquartile range) = 2.8 pg/mL (1.8-4.2)] than in controls [0.9 pg/mL (0-3.5)] (P = 0.02), but no association was observed between serum IL-10 levels or lipopolysaccharide-induced IL-10 secretion and the IL-10 promoter haplotypes. These data suggest that the IL-10 promoter haplotype that produces higher levels of cytokine is associated with SLE in patients from Canary Islands.

摘要

本研究的目的是检验多态性白细胞介素(IL)-10启动子区域中的几个等位基因变体是否与来自加那利群岛的西班牙患者患系统性红斑狼疮(SLE)的风险增加相关。对来自西班牙加那利群岛的SLE患者和健康对照者分析了IL-10启动子-4000和-1200位置的微卫星(MS)(分别为IL10R和IL10G)以及-1082G/A、-819C/T和-592C/A位置的单核苷酸多态性(SNP)。我们发现SNP而非MS与SLE相关。GCC单倍型频率在SLE患者中(0.43)显著高于健康供者(0.33)[P = 0.02;比值比(OR)= 1.50(95%可信区间(CI)= 1.06 - 2.14)],而ACC单倍型在患者中的比例较低(0.28对0.37)[P = 0.02;OR = 0.64(95%CI = 0.44 - 0.92)]。为评估基因型的功能作用,通过酶联免疫吸附测定(ELISA)对患者和对照者的血清IL-10水平进行定量。此外,体外评估了健康对照者单核细胞经脂多糖诱导的IL-10分泌。患者的血清IL-10水平[中位数(四分位间距)= 2.8 pg/mL(1.8 - 4.2)]高于对照者[0.9 pg/mL(0 - 3.5)](P = 0.02),但未观察到血清IL-10水平或脂多糖诱导的IL-10分泌与IL-10启动子单倍型之间存在关联。这些数据表明,产生较高细胞因子水平的IL-10启动子单倍型与来自加那利群岛的患者的SLE相关。

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