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慢性疲劳综合征细胞因子基因多态性的首次研究:肿瘤坏死因子-857和干扰素γ 874稀有等位基因的阳性关联

A first study of cytokine genomic polymorphisms in CFS: Positive association of TNF-857 and IFNgamma 874 rare alleles.

作者信息

Carlo-Stella N, Badulli C, De Silvestri A, Bazzichi L, Martinetti M, Lorusso L, Bombardieri S, Salvaneschi L, Cuccia M

机构信息

Immunogenetics Laboratory, Dept. of Genetics and Microbiology, University of Pavia, Italy.

出版信息

Clin Exp Rheumatol. 2006 Mar-Apr;24(2):179-82.

Abstract

OBJECTIVE

In the past two years we have developed a biological bank of genomic DNA, cDNA, serum and red blood cells of Italian patients with certified CFS from the two Italian referral centers for the syndrome. Recent studies have shown an imbalance in cytokine production in disease states similar to Chronic Fatigue Syndrome (CFS), such as sickness behavior, both in animals and in humans. However we notice that serum cytokine concentrations are often inconstant and degrade rapidly. With this in mind, we investigated cytokine gene polymorphisms in 80 Italian patients with CFS in order to ascertain whether in this group of patients it is possible to describe a genetic predisposition to an inflammatory response.

METHODS

We analyzed the promoter polymorphisms of IL-10, IL-6 and the IFNgamma 874 T/A polymorphism in intron 1 with a PCR-SSP method (Cytogen One Lambda Inc. Canoga Park, CA, U.S.A) in 54 patients and TNF-308 G/A and -857 C/T promoter polymorphisms with a PCR-RFLP method (in 54 and 80 patients respectively).

RESULTS

There is a highly significant increase of TNF -857 TT and CT genotypes (p = 0.002) among patients with respect to controls and a significant decrease of IFN gamma low producers (A/A) (p = 0.04) among patients with respect to controls.

CONCLUSIONS

We hypothesize that CFS patients can have a genetic predisposition to an immunomodulatory response of an inflammatory nature probably secondary to one or more environmental insults of unknown nature.

摘要

目的

在过去两年中,我们建立了一个生物样本库,其中包含来自意大利两个该综合征转诊中心的经认证的慢性疲劳综合征(CFS)患者的基因组DNA、互补DNA(cDNA)、血清和红细胞。最近的研究表明,在与慢性疲劳综合征(CFS)类似的疾病状态下,如疾病行为,动物和人类的细胞因子产生均存在失衡。然而,我们注意到血清细胞因子浓度往往不稳定且降解迅速。考虑到这一点,我们调查了80名意大利CFS患者的细胞因子基因多态性,以确定在这组患者中是否有可能描述炎症反应的遗传易感性。

方法

我们采用聚合酶链反应-序列特异性引物(PCR-SSP)方法(美国加利福尼亚州卡诺加公园的Cytogen One Lambda公司)分析了54例患者白细胞介素-10(IL-10)、白细胞介素-6的启动子多态性以及第1内含子中干扰素γ874 T/A多态性,并采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法分别分析了54例和80例患者肿瘤坏死因子-308 G/A和-857 C/T启动子多态性。

结果

与对照组相比,患者中肿瘤坏死因子-857 TT和CT基因型显著增加(p = 0.002),与对照组相比,患者中干扰素γ低产生者(A/A)显著减少(p = 0.04)。

结论

我们推测,慢性疲劳综合征患者可能具有炎症性质的免疫调节反应的遗传易感性,这可能继发于一种或多种未知性质的环境损伤。

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