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MTX通路基因变异,红细胞甲状腺酸多重胺,以及类风湿性关节炎治疗结果
Peihong Wang1, Cuilv Liang1, Limei Lin1
1Department of Pharmacy, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.
在这项研究中,红细胞甲状腺酸多聚氨酸 (MTXPGs) 并没有预测类风湿性关节炎 (RA) 治疗结果. 然而,特定的基因变异 (SLCO1B1,GGH,ABCB1) 可能成为RA患者MTX反应的潜在标志物.
科学领域:
- 药物基因组学 药物基因组学
- 类风湿病学 类风湿病学
- 药物新陈代谢 药物新陈代谢
背景情况:
- 在类风湿性关节炎 (RA) 中,甲基酸 (MTX) 的反应在患者之间有显著的差异.
- 红细胞甲基酸多胺酸 (MTXPGs) 和MTX通路药物遗传学在预测MTX结果中的作用尚不清楚.
研究的目的:
- 调查MTX通路基因多态性,红细胞MTXPG水平,以及RA患者的MTX治疗疗效和药物不良反应 (ADRs) 之间的关联.
- 在汉族中国RA队列中探索MTX反应的潜在遗传标记.
主要方法:
- 在140名汉族中国RA患者接受稳定低剂量口服MTX的横截面研究.
- 使用MassARRAY对MTX途径基因进行基因定型.
- 通过LC-MS/MS量化红细胞MTXPG水平 (1-6).
- 治疗疗效的评估 (ACR20,临床尺度) 和不良反应.
主要成果:
- 红细胞MTXPG水平与MTX疗效或ADRs没有相关性.
- SLCO1B1 521T>C多态性与较低的MTXPG水平有关.
- GGH 401C>T多态性与ACR20反应的减少有关.
- SLCO1B1和ABCB1变异与较高的患者报告结果得分 (PHGA,HAQ) 相关联.
结论:
- 红细胞MTXPG水平不能预测低剂量MTX治疗的RA患者的临床结果.
- SLCO1B1,GGH和ABCB1基因变异显示出可能成为RA中MTX反应的探索性生物标志物.
- 需要进行更大规模的前性研究来验证这些遗传标记.
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