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人类白细胞抗原-G的14碱基对多态性作为心脏移植和环孢素治疗监测的遗传决定因素。

14-Base pair polymorphism of human leukocyte antigen-G as genetic determinant in heart transplantation and cyclosporine therapy monitoring.

作者信息

Torres M I, Luque J, Lorite P, Isla-Tejera B, Palomeque T, Aumente M D, Arizon J, Peña J

机构信息

Department of Experimental Biology, University of Jaen, Jaen, Spain.

出版信息

Hum Immunol. 2009 Oct;70(10):830-5. doi: 10.1016/j.humimm.2009.07.012. Epub 2009 Jul 25.

DOI:10.1016/j.humimm.2009.07.012
PMID:19638290
Abstract

The 14-base pair (bp) polymorphism within the HLA-G gene has been investigated in heart transplant patients for the first time. The 14-bp polymorphism is associated with HLA-G mRNA stability and the patterns of alternative isoforms splicing, and therefore may influence the functionality of the HLA-G molecule. In heart transplantation, the highest production of soluble HLA-G was related to the -14/-14-bp genotype in the pre- and post-transplantation periods. Our study findings showed that the 14-bp polymorphism of the HLA-G gene influenced the expression of soluble HLA-G in heart transplantation and accordingly resulted in low rejection rates, being a possible marker of genetic variability associated with heart transplantation. In addition, the 14-bp polymorphism of the HLA-G gene is related to the absorber status of cyclosporine of each individual patient, and is useful for determining the oral dose of cyclosporine to manage patients (to adjust immunosuppressive protocols) so as to minimize the risk of a low or high immunosuppression and the side effects in the early stages of heart transplantation.

摘要

首次在心脏移植患者中对HLA - G基因内14个碱基对(bp)的多态性进行了研究。14 - bp多态性与HLA - G mRNA稳定性及可变异构体剪接模式相关,因此可能影响HLA - G分子的功能。在心脏移植中,可溶性HLA - G的最高产量在移植前和移植后阶段均与 - 14 / - 14 - bp基因型相关。我们的研究结果表明,HLA - G基因的14 - bp多态性影响心脏移植中可溶性HLA - G的表达,从而导致低排斥率,这可能是与心脏移植相关的遗传变异性的一个标志。此外,HLA - G基因的14 - bp多态性与每个患者的环孢素吸收状态相关,有助于确定环孢素的口服剂量以管理患者(调整免疫抑制方案),从而在心脏移植早期将免疫抑制不足或过度及副作用的风险降至最低。

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