Differential transcriptional expresion of the polymorphic myxovirus resistance protein A in response to interferonalpha treatment

Differential transcriptional expresion of the polymorphic myxovirus resistance protein A in response to interferonalpha treatment
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DOI:
10.1097/01.fpc.0000114718.42625.a1
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发表时间:
2004-03-01
期刊:
PHARMACOGENETICS
影响因子:
--
通讯作者:
Reyes-Engel, A
Reyes-Engel, A
中科院分区:
其他
文献类型:
--
作者:
Fernández-Arcás, N;Blanco, A;Reyes-Engel, A

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研究粘病毒耐药蛋白A(MxA)mRNA水平,以确定基因启动子区-88位核苷酸的单核苷酸多态性,以确定个体对干扰素(IFN)-α(2)的特异性反应,这可能预测对IFN-α治疗的反应。我们通过逆转录和实时聚合酶链反应定量测定了22名健康献血者的外周血单个核细胞(PBMC)在IFN-α(2)诱导下的MxA表达,并与MxA启动子中的G/T多态性相关。在体外实验中,所有受试者对IFN-α 2的反应中MxA mRNA显著上调(平均53倍)(P < 0.01)。与G/T多态性相关的MxAmRNA诱导表达的比较显示,突变型等位基因(GT或TT)携带者PBMC中MxAmRNA的诱导表达是野生型等位基因(GG)纯合子的4.26倍(P < 0.001)。我们认为IFN诱导型MxA的表达受到MxA启动子中单核苷酸多态性的影响,该多态性可以识别对IFN-α的个体反应(2)。(C)2004年利平科特威廉姆斯威尔金斯。
Levels of myxovirus resistance protein A (MxA) mRNA were studied for a single nucleotide polymorphism in the promoter region at nucleotide position -88 of the gene to identify individual-specific responses to interferon (IFN)-alpha(2) that might predict responsiveness to IFN-alpha therapy. We quantified MxA expression by reverse transcription and real-time polymerase chain reaction in peripheral blood mononuclear cells (PBMC) in vitro, induced by IFN-alpha(2), from 22 healthy donors, in relation with G/T polymorphism located in the promoter of the MxA. MxA mRNA was significantly upregulated in all subjects (mean of 53-fold) in response to IFN-alpha(2) in vitro (P < 0.01). Comparison of the inducibility of MxA mRNA expression in relation with G/T polymorphism showed a 4.26-fold higher induction of MxA mRNA levels in PBMC from carriers of the mutant allele (GT or TT) than homozygotes with the wild-type allele (GG) (P < 0.001). We propose that expression of the IFN-inducible MxA is affected by a single nucleotide polymorphism in the MxA promoter which can identify an individual response to IFN-alpha(2). (C) 2004 Lippincott Williams Wilkins.