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不明原因复发性流产中的细胞因子基因多态性

Cytokine gene polymorphisms in recurrent pregnancy loss of unknown cause.

作者信息

Prigoshin Norma, Tambutti M, Larriba J, Gogorza S, Testa R

机构信息

Histocompatibility and Immunogenetics Section, Diagnostic Department, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.

出版信息

Am J Reprod Immunol. 2004 Jul;52(1):36-41. doi: 10.1111/j.1600-0897.2004.00179.x.

DOI:10.1111/j.1600-0897.2004.00179.x
PMID:15214940
Abstract

PROBLEM

According to previous investigations, certain cytokines may play a role in recurrent pregnancy loss (RPL). Significantly different levels of Th1/Th2 cytokines are produced by normal pregnant women compared with women with RPL of unknown cause.

OBJECTIVE

We have studied the polymorphism of cytokine genes which are related to the amount of the cytokine produced. High (H), intermediate (I) and low (L) cytokine responses can be predicted from the cytokine genotype.

MATERIAL AND METHODS

The genetic polymorphism of Th1 cytokine [i.e. interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha] and Th2 cytokines [i.e. interleukin (IL)-6, IL-10] and the transforming growth factor (TGF)-beta were studied by polymerase chain reaction-sequence specific primers (PCR-SSP) in the DNA of PBC from 41 women with RPL and 54 control women who had at least two children and without known pregnancy losses.

RESULTS

The results showed: (i) no evidence of associations between patients and controls concerning the Th1: TNF-alpha; the Th2: IL-6 and IL-10 and the TGF-beta genotype, (ii) significative association between RPL versus controls concerning IFN-gamma +874 A --> T: T/A genotype was increased in the patient group in comparison with the control group (65% versus 35.8%) (P = 0.01) and there was a statistical disminution in the frequency of the A/A (L) genotype between the patient groups in comparison with the control group (20% versus 41.5%) (P = 0.04).

CONCLUSION

This finding would support the concept of involvement of IFN-gamma +874 A --> T in the pathogenesis of RPL of unknown cause in the Caucasian Argentine population.

摘要

问题

根据先前的研究,某些细胞因子可能在复发性流产(RPL)中起作用。与原因不明的复发性流产女性相比,正常孕妇产生的Th1/Th2细胞因子水平存在显著差异。

目的

我们研究了与细胞因子产生量相关的细胞因子基因多态性。可以从细胞因子基因型预测高(H)、中(I)和低(L)细胞因子反应。

材料与方法

采用聚合酶链反应-序列特异性引物(PCR-SSP)技术,对41例复发性流产女性和54例至少有两个孩子且无已知流产史的对照女性外周血单个核细胞(PBC)DNA中的Th1细胞因子[即干扰素(IFN)-γ和肿瘤坏死因子(TNF)-α]、Th2细胞因子[即白细胞介素(IL)-6、IL-10]和转化生长因子(TGF)-β的基因多态性进行研究。

结果

结果显示:(i)患者与对照在Th1:TNF-α;Th2:IL-6和IL-10以及TGF-β基因型方面无关联证据,(ii)复发性流产患者与对照相比,IFN-γ +874 A→T:T/A基因型存在显著关联,患者组该基因型比例高于对照组(65%对35.8%)(P = 0.01),且患者组A/A(L)基因型频率较对照组有统计学降低(20%对41.5%)(P = 0.04)。

结论

这一发现支持IFN-γ +874 A→T参与白种阿根廷人群原因不明的复发性流产发病机制的概念。

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