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首页> 外文期刊>Pharmacogenomics and Personalized Medicine >Genetic polymorphism of the methotrexate transporter ABCG2, blood pressure and markers of arterial function in patients with rheumatoid arthritis: repeated cross-sectional study
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Genetic polymorphism of the methotrexate transporter ABCG2, blood pressure and markers of arterial function in patients with rheumatoid arthritis: repeated cross-sectional study

机译：类风湿关节炎患者甲氨蝶呤转运蛋白ABCG2的遗传多态性，血压和动脉功能标志物

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Purpose: Methotrexate (MTX) treatment is associated with lower blood pressure (BP) and arterial stiffness in rheumatoid arthritis (RA). We investigated associations between single-nucleotide polymorphism (SNP) of the ATP-binding cassette efflux transporter gene ABCG2 (rs2231142), BP, and arterial stiffness in RA patients treated with MTX. Patients and methods: Clinical and 24-hour peripheral and central BP, arterial wave reflection (Augmentation Index, AIx), arterial stiffness (Pulse Wave Velocity, PWV), and intracellular MTX polyglutamate (MTXPGs) concentrations were assessed in 56 RA patients on stable treatment with MTX using a repeated cross-sectional study design with measurements at baseline and after 8 months. Results: Majority of the RA patients were homozygotes for the normal allele (CC, n=46) whereas 10 were rs2231142 heterozygotes (AC, n=10). MTXPGs concentrations were non-significantly higher in AC when compared to CC (144.3 vs 116.3 nmol/L packed RBCs, P =0.10). At baseline, the AC group had significantly lower age-adjusted clinical systolic BP (SBP) ( P =0.01), 24-hour peripheral SBP ( P =0.003), and central SBP ( P =0.02) when compared to the CC group. However, AIx and PWV values were not significantly different between the two groups. When data from both visits were combined in a single analysis, and additionally adjusted for visit, gender, body mass index, and Disease Activity Score 28, the trend in SBP differences between-groups persisted but was no longer significant. Conclusion: Future studies are required to test the hypothesis that this genetic polymorphism is associated with lower BP, arterial stiffness, and possibly, cardiovascular risk, in RA patients treated with MTX.
机译：目的：甲氨蝶呤（MTX）治疗与类风湿关节炎（RA）的较低血压（BP）和动脉僵硬相关。我们调查了接受MTX治疗的RA患者中ATP结合盒外排转运基因ABCG2（rs2231142），BP的单核苷酸多态性（SNP）与动脉僵硬度之间的关联。患者和方法：在稳定的56位RA患者中评估了临床和24小时的周围和中央BP，动脉波反射（增强指数，AIx），动脉僵硬度（脉搏波速度，PWV）和细胞内MTX聚谷氨酸盐（MTXPGs）浓度使用重复性横断面研究设计进行MTX治疗，在基线和8个月后进行测量。结果：RA患者的大多数为正常等位基因的纯合子（CC，n = 46），而rs2231142杂合子为10（AC，n = 10）。与CC相比，AC中的MTXPGs浓度无显着增加（144.3对116.3 nmol / L填充的RBC，P = 0.10）。与CC组相比，AC组在基线时的年龄校正后的临床收缩压（SBP）（P = 0.01），24小时外周血SBP（P = 0.003）和中枢性SBP（P = 0.02）明显较低。但是，两组之间的AIx和PWV值没有显着差异。当将两次就诊的数据合并到一个分析中，并针对就诊，性别，体重指数和疾病活动评分28进行额外调整后，两组之间的SBP差异趋势仍然存在，但不再显着。结论：需要进一步的研究来检验这种基因多态性与接受MTX治疗的RA患者的较低的BP，动脉僵硬度以及可能的心血管风险相关的假设。

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