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白细胞介素-2 基因多态性影响重症肌无力患者他克莫司的反应。

IL-2 gene polymorphisms affect tacrolimus response in myasthenia gravis.

机构信息

Department of Neurology, Xiangya Hospital, Central South University, 87 Xiangya road, Changsha, Hunan, China.

出版信息

Eur J Clin Pharmacol. 2019 Jun;75(6):795-800. doi: 10.1007/s00228-019-02642-z. Epub 2019 Feb 7.

DOI:10.1007/s00228-019-02642-z
PMID:30729267
Abstract

PURPOSE

The IL-2 gene polymorphisms have been reported to be associated with the development of autoimmune disease. However, there are no published studies examining the influence of the IL-2 gene polymorphisms on the response of myasthenia gravis (MG) patients to tacrolimus (Tac). The goal of this study was to investigate the relationship between the polymorphisms of IL-2 and Tac response in MG patients.

METHODS

Ninety-two MG patients treated with Tac were studied, including 57 Tac-effective patients and 35 Tac-ineffective patients. Then, we selected four single-nucleotide polymorphisms (SNPs: rs2069776, rs2069772, rs2069762, rs2069763) in the IL-2 gene. Next, we analyzed the distribution of genotypes, allelic frequencies of SNPs, and haplotype frequencies among polymorphisms in the two groups of patients.

RESULTS

The distribution of the allelic frequency of the rs2069762 variant differed between the Tac-effective and Tac-ineffective patients (P = 0.02). Genotypes G/T and G/G of rs2069762 were differently distributed between the two groups when the wild genotype T/T was assigned as a reference (P < 0.001 for G/T; P = 0.003 for G/G). Patients with the TAGG haplotype tended to be Tac-ineffective (P < 0.001, OR: 0.15, 95% CI: 0.05-0.43).

CONCLUSION

Myasthenia gravis patients with the rs2069762 variant, rs2069762 G/T and G/G genotype, and TAGG haplotype for IL-2 tended to respond poorly to Tac treatment.

摘要

目的

IL-2 基因多态性与自身免疫性疾病的发生有关。然而,目前尚无研究探讨 IL-2 基因多态性对重症肌无力(MG)患者他克莫司(Tac)反应的影响。本研究旨在探讨 IL-2 基因多态性与 MG 患者 Tac 反应的关系。

方法

研究了 92 例接受 Tac 治疗的 MG 患者,包括 57 例 Tac 有效患者和 35 例 Tac 无效患者。然后,我们在 IL-2 基因中选择了四个单核苷酸多态性(SNP:rs2069776、rs2069772、rs2069762、rs2069763)。接着,我们分析了两组患者中 SNP 基因型、等位基因频率和单倍型频率的分布。

结果

rs2069762 等位基因频率在 Tac 有效组和 Tac 无效组之间存在差异(P=0.02)。当将野生基因型 T/T 作为参考时,rs2069762 的 G/T 和 G/G 基因型在两组之间的分布不同(G/T:P<0.001;G/G:P=0.003)。TAGG 单倍型患者倾向于 Tac 无效(P<0.001,OR:0.15,95%CI:0.05-0.43)。

结论

IL-2 的 rs2069762 变异、rs2069762 G/T 和 G/G 基因型以及 TAGG 单倍型的 MG 患者对 Tac 治疗的反应可能较差。

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