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白细胞介素-6 -174G/C基因变异与甲氨蝶呤治疗银屑病关节炎患者疗效的关系

Relationship Between Interleukin-6 -174G/C Genetic Variant and Efficacy of Methotrexate Treatment in Psoriatic Arthritis Patients.

作者信息

Sokolik Renata, Iwaszko Milena, Świerkot Jerzy, Wysoczańska Barbara, Korman Lucyna, Wiland Piotr, Bogunia-Kubik Katarzyna

机构信息

Department of Rheumatology and Internal Medicine, Wrocław Medical University, Wrocław, Poland.

Laboratory of Clinical Immunogenetics and Pharmacogenetics, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.

出版信息

Pharmgenomics Pers Med. 2021 Jan 28;14:157-166. doi: 10.2147/PGPM.S264555. eCollection 2021.

Abstract

INTRODUCTION

The purpose of the study was to investigate whether single-nucleotide polymorphisms (SNPs) IL-6 -174 G/C and IL-6R Asp358Ala are associated with susceptibility to psoriatic arthritis (PsA) or affect response to treatment with methotrexate (MTX).

PATIENTS AND METHODS

Seventy-four patients diagnosed with PsA and qualified for MTX treatment were enrolled to the study. The control group consisted of 120 healthy individuals. Polymorphisms IL-6 -174 G/C and IL-6R Asp358Ala were genotyped using a polymerase chain reaction (PCR) amplification employing LightSNiP assays.

RESULTS

A significant association between the IL-6 -174 CC genotype and an improved clinical outcome of MTX therapy was observed. A good response was more frequently observed among PsA patients bearing the IL-6 -174 CC genotype than patients with the GC or GG genotypes ( = 0.007). On the other hand, patients carrying the IL-6 -174 GC genotype less frequently responded to MTX treatment as compared to patients with other genotypes ( = 0.006). With respect to the IL-6R Asp358Ala SNP, there were no significant differences in genotype and allelic frequencies in relation to clinical outcome of MTX treatment. No association was found between the IL-6 -174 G/C or IL-6R Asp358Ala SNPs and PsA susceptibility.

CONCLUSION

Results from this study provide evidence that the IL-6 -174 G/C polymorphism might influence efficacy of MTX treatment.

摘要

引言

本研究旨在调查单核苷酸多态性(SNP)白细胞介素-6(IL-6)-174G/C和IL-6受体(IL-6R)Asp358Ala是否与银屑病关节炎(PsA)易感性相关,或影响甲氨蝶呤(MTX)治疗反应。

患者与方法

74例诊断为PsA且符合MTX治疗条件的患者纳入本研究。对照组由120名健康个体组成。采用LightSNiP分析的聚合酶链反应(PCR)扩增对IL-6 -174G/C和IL-6R Asp358Ala多态性进行基因分型。

结果

观察到IL-6 -174CC基因型与MTX治疗的临床疗效改善之间存在显著关联。携带IL-6 -174CC基因型的PsA患者比携带GC或GG基因型的患者更常出现良好反应(P = 0.007)。另一方面,与其他基因型患者相比,携带IL-6 -174GC基因型的患者对MTX治疗的反应较少(P = 0.006)。关于IL-6R Asp358Ala SNP,MTX治疗的临床疗效在基因型和等位基因频率方面无显著差异。未发现IL-6 -174G/C或IL-6R Asp358Ala SNP与PsA易感性之间存在关联。

结论

本研究结果提供了证据表明IL-6 -174G/C多态性可能影响MTX治疗的疗效。

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A global reference for human genetic variation.人类遗传变异的全球参考。
Nature. 2015 Oct 1;526(7571):68-74. doi: 10.1038/nature15393.

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