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在阿尔及利亚西部人群中,亚甲基四氢叶酸还原酶(MTHFR)基因c.677 C>T、MTHFR基因c.1298 A>C以及三磷酸腺苷结合盒转运蛋白B1(ABCB1)基因c.3435 C>T多态性与类风湿关节炎甲氨蝶呤治疗效果之间无相关性。

No correlation between MTHFR c.677 C > T, MTHFR c.1298 A > C, and ABCB1 c.3435 C > T polymorphisms and methotrexate therapeutic outcome of rheumatoid arthritis in West Algerian population.

作者信息

Boughrara Wefa, Benzaoui Ahmed, Aberkane Meriem, Moghtit Fatima Zohra, Dorgham Samia, Lardjam-Hetraf Aicha Sarah, Ouhaibi-Djellouli Hadjer, Teixeira Elisabeth Petit, Boudjema Abdallah

机构信息

Laboratoire de génétique moléculaire et cellulaire, Université des sciences et de la technologie d'Oran Mohamed Boudiaf (USTO-MB), BP 1505, El-M'naouar, 31000, Oran, Algeria.

Ecole préparatoire en science de la nature et de la vie d'Oran (EPSNVO), Oran, Algeria.

出版信息

Inflamm Res. 2017 Jun;66(6):505-513. doi: 10.1007/s00011-017-1034-6. Epub 2017 Mar 15.

Abstract

CONTEXT

The c.677 C > T and c.1298 A > C polymorphisms of methylenetatrahydrofolate reductase (MTHFR) gene and c.3435 C > T polymorphism of ATP-Binding cassette B1 (ABCB1) gene are reported as pharmacogenetic markers, influencing the methotrexate (MTX) therapeutic outcome in rheumatoid arthritis (RA) patients.

OBJECTIVES

The aims of this study were to determine the relationship between these polymorphisms and clinical response and/or adverse drug reaction (ADRs) to MTX treatment.

MATERIALS AND METHODS

The cohort of our study was composed of 110 RA patients of the West Algerian population. The clinical response was evaluated using the disease activity score 28 (DAS28) and the ADRs were collected after physical examination of patients. All samples were genotyped for theses polymorphisms by TaqMan allelic discrimination assay.

RESULTS

Based on EULAR criteria, 59.09% RA patients were responders and ADRs were observed in 40.9% patients. The frequency distribution of these three polymorphisms was similar between the responders and the non-responders. The same result was found on ADRs study and no significant difference of distribution between the presence of ADRs group and absence of ADRs group was observed.

DISCUSSION

Our study joins the results that found in others population in the world.

CONCLUSION

We have demonstrated, for the first time in the West Algerian population, that these polymorphisms were not predictive for clinical response and/or ADRs to MTX therapeutic outcome.

摘要

背景

亚甲基四氢叶酸还原酶(MTHFR)基因的c.677 C>T和c.1298 A>C多态性以及ATP结合盒转运体B1(ABCB1)基因的c.3435 C>T多态性被报道为药物遗传学标志物,影响类风湿关节炎(RA)患者甲氨蝶呤(MTX)的治疗效果。

目的

本研究旨在确定这些多态性与MTX治疗的临床反应和/或药物不良反应(ADR)之间的关系。

材料与方法

我们的研究队列由110名来自阿尔及利亚西部人群的RA患者组成。使用疾病活动评分28(DAS28)评估临床反应,并在对患者进行体格检查后收集ADR。通过TaqMan等位基因鉴别分析对所有样本进行这些多态性的基因分型。

结果

根据欧洲抗风湿病联盟(EULAR)标准,59.09%的RA患者有反应,40.9%的患者观察到ADR。这三种多态性的频率分布在有反应者和无反应者之间相似。在ADR研究中也得到了相同的结果,ADR存在组和不存在组之间的分布没有显著差异。

讨论

我们的研究与世界其他人群的研究结果一致。

结论

我们首次在阿尔及利亚西部人群中证明,这些多态性不能预测MTX治疗结果的临床反应和/或ADR。

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