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首页> 外文期刊>Pharmacogenetics and genomics >Interaction of genes from influx-metabolism-efflux pathway and their influence on methotrexate efficacy in rheumatoid arthritis patients among Indians.
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Interaction of genes from influx-metabolism-efflux pathway and their influence on methotrexate efficacy in rheumatoid arthritis patients among Indians.

机译：在印度人中，类风湿关节炎患者的代谢代谢外流通路基因相互作用及其对甲氨蝶呤疗效的影响。

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OBJECTIVE: Methotrexate (MTX) is the drug of choice for rheumatoid arthritis (RA) but is effective only in around 60% of treated patients. Bioavailability of MTX may be a major determinant of response status and this may be governed by variations in MTX receptor and transporter genes and genes responsible for polyglutamation and deconjugation. We investigated the contribution of single nucleotide polymorphisms (SNPs) in RFC, FOLR1, FPGS, GGH and MDR1 genes to MTX response in RA patients from North India. METHODS: RA patients recruited using American College of Rheumatology criteria, were categorized into good and poor responders to MTX, based on disease activity score. A total of 17 SNPs from the above mentioned genes were genotyped and tested for association with MTX response using [chi]2 test; logistic regression along with clinical variables; and gene-gene interaction using multifactor dimensionality reduction (MDR). RESULTS: One novel synonymous SNP Ala324Ala (972 G > A) was identified in RFC gene.The CT genotype of C3435T in MDR1 gene conferred almost twice the risk of poor response [[chi]2 = 5.85, P = 0.01, odds ratio (95% confidence interval) = 1.97 (1.13-3.42)] and was retained in binary logistic regression [B = 0.66, P = 0.025, adjusted odds ratio (95% confidence interval) = 1.93(1.09-3.42)]. Significant interaction between SNPs in GGH and MDR1 genes seems promising. CONCLUSION: Interactions between genes coding for deconjugation and transporter seem to be important determinants of MTX response in RA but replication and functional studies would be confirmatory.
机译：目的：甲氨蝶呤（MTX）是类风湿关节炎（RA）的首选药物，但仅在约60％的治疗患者中有效。 MTX的生物利用度可能是反应状态的主要决定因素，这可能由MTX受体和转运蛋白基因以及负责聚谷氨酸和解偶联的基因的变异所决定。我们调查了来自印度北部的RA患者的RFC，FOLR1，FPGS，GGH和MDR1基因中的单核苷酸多态性（SNP）对MTX反应的影响。方法：根据疾病活动评分，根据美国风湿病学会标准招募的RA患者按对MTX的反应分为好反应者和差反应者。对来自上述基因的总共17个SNP进行基因分型，并使用χ2检验测试其与MTX应答的关联。逻辑回归与临床变量;使用多维度降维（MDR）进行基因与基因的相互作用。结果：在RFC基因中鉴定出一种新的同义SNP Ala324Ala（972 G> A）。MDR1基因中C3435T的CT基因型带来的不良反应风险几乎是两倍[χ2= 5.85，P = 0.01，优势比（ 95％置信区间）= 1.97（1.13-3.42）]并保留在二元logistic回归中[B = 0.66，P = 0.025，调整后的优势比（95％置信区间）= 1.93（1.09-3.42）]。 GGH和MDR1基因中SNP之间的显着相互作用似乎很有希望。结论：解偶联编码基因和转运蛋白之间的相互作用似乎是RA中MTX应答的重要决定因素，但复制和功能研究将是证实性的。

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