关联MTRR 66 A/G和MTR 2756 A/G的多形态和响应在类风湿性关节炎中使用甲索德. 一个元分析
1From the Department of Rheumatology, Korea University College of Medicine, Seoul, Korea.
概括
这次元分析发现,氨酸合成酶减少酶 (MTRR) 66 A/G基因型与类风湿性关节炎患者的更好的甲状腺激素 (MTX) 反应有关,特别是在更大的研究中. 氨酸合成酶 (MTR) 2756 A/G多态性与MTX反应没有显著的关联.
科学领域:
- 药物遗传学 药物遗传学
- 类风湿病学 类风湿病学
- 遗传学 遗传学 是一个
背景情况:
- 甲托雷克萨特 (MTX) 是类风湿性关节炎 (RA) 的基石疗法.
- 个人对MTX的反应有很大差异,需要个性化治疗方法.
- 遗传多态性,包括叶酸通路基因中的基因,可能会影响MTX的疗效.
研究的目的:
- 调查RA中MTX响应与氨酸合成酶减少酶 (MTRR) 66 A/G和氨酸合成酶 (MTR) 2756 A/G中的多态性之间的关联.
- 进行元分析,巩固这些遗传关联的证据.
主要方法:
- 在MEDLINE,EMBASE,Web of Science和Cochrane数据库中进行系统的文献搜索.
- 对八项研究的元分析,研究了MTRR 66 A/G和MTR 2756 A/G多态度与RA中MTX反应的关系.
- 基于样本大小,种族和随访时间的分层分析.
主要成果:
- 在MTRR 66 A/G (GG + GA基因型) 和MTX响应性 (OR = 1.289,p = 0.059) 之间没有显著的总体关联.
- 在更大的样本大小 (n ≥ 150) (OR = 1.343,p = 0.039) 的研究中发现了显著的关联,但在较小的研究中没有发现.
- 没有观察到MTR 2756 A/G多态 (GG + GA基因型) 与MTX响应 (OR = 1.053,p = 0.751) 的显著关联.
结论:
- MTRR 66 A/G GG + GA基因型可能与RA中对MTX的更好的反应有关,特别是在较大的队列中,这表明它是一个潜在的药物遗传标记.
- 在RA中,MTR 2756 A/G多态似乎没有显著影响MTX治疗反应.
- 鉴于目前证据强度的局限性,需要对更大样本进行进一步的研究,以确认MTRR 66 A/G和MTX反应之间的关联.
相关概念视频
01:11Genome-wide Association Studies-GWAS
Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
GWAS does not require the identification of the target gene involved in...
01:29Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
01:27Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase
Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...