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韩国人中白细胞介素18基因单核苷酸多态性及单倍型与特应性皮炎的关联

Association of the single-nucleotide polymorphism and haplotype of the interleukin 18 gene with atopic dermatitis in Koreans.

作者信息

Kim E, Lee J-E, Namkung J-H, Park J-H, Kim S, Shin E-S, Cho E-Y, Yang J-M

机构信息

Department of Dermatology, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea.

出版信息

Clin Exp Allergy. 2007 Jun;37(6):865-71. doi: 10.1111/j.1365-2222.2007.02717.x.

Abstract

BACKGROUND

IL-18 is a proinflammatory cytokine that plays an important role for T-helper type 1 (Th1) and Th2 cytokine in the presence/absence of IL-12. It has been recently shown that human IL-18 plays a role in atopic dermatitis (AD) by enhancing IL-4 and IL-13 production and by stimulating the synthesis of IgE.

OBJECTIVE

We wanted to evaluate the associations of single-nucleotide polymorphism (SNP) and the haplotype in the IL-18 gene, hence we performed genotyping for the SNPs in the IL-18 gene in AD patients and normal controls.

METHOD

We genotyped three SNPs from the IL-18 gene for the 1120 case-control samples (646 AD patients and 474 normal controls). We measured the serum IL-18, IL-4 and IL-13 concentrations in 74 individuals (25 ADe, 25 ADi and 24 controls) by performing ELISA.

RESULT

The rs795467 SNP and haplotype T-T-C were significantly associated with AD, and especially between the ADe and normal control groups (P=0.03 and 0.01). The serum IL-18 concentration was higher in the AD group than in the normal controls without any correlation with the rs795467 polymorphism. We did not find any correlations between the serum IL-18 levels and the SCORing atopic dermatitis index, the blood eosinophil counts and the ECP, and there was no correlation between the serum IL-18 levels and the serum IL-4 and IL-13 levels.

CONCLUSION

We found that the one SNP and the haplotype T-T-C were strongly associated with the allergic type of AD, but not with the non-allergic intrinsic type. These data support the hypothesis that IL-18 up-regulates IgE production, yet more experiments will be needed to prove the in vivo involvement of Th2 cytokine.

摘要

背景

白细胞介素-18(IL-18)是一种促炎细胞因子,在白细胞介素-12存在或不存在的情况下,对1型辅助性T细胞(Th1)和Th2细胞因子发挥重要作用。最近研究表明,人类IL-18通过增强IL-4和IL-13的产生以及刺激IgE的合成,在特应性皮炎(AD)中发挥作用。

目的

我们想要评估IL-18基因中的单核苷酸多态性(SNP)和单倍型之间的关联,因此我们对AD患者和正常对照者的IL-18基因中的SNP进行了基因分型。

方法

我们对1120例病例对照样本(646例AD患者和474例正常对照)的IL-18基因中的三个SNP进行了基因分型。我们通过酶联免疫吸附测定法(ELISA)测量了74名个体(25名湿疹型AD患者、25名内源性AD患者和24名对照)的血清IL-18、IL-4和IL-13浓度。

结果

rs795467 SNP和单倍型T-T-C与AD显著相关,尤其是在湿疹型AD组和正常对照组之间(P = 0.03和0.01)。AD组的血清IL-18浓度高于正常对照组,且与rs795467多态性无相关性。我们未发现血清IL-18水平与特应性皮炎评分指数、血液嗜酸性粒细胞计数和嗜酸性粒细胞阳离子蛋白之间存在任何相关性,血清IL-18水平与血清IL-4和IL-13水平之间也无相关性。

结论

我们发现一个SNP和单倍型T-T-C与过敏性AD密切相关,但与非过敏性内源性AD无关。这些数据支持IL-18上调IgE产生这一假说,但还需要更多实验来证明Th2细胞因子在体内的作用。

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