Methylenetetrahydrofolate reductase gene polymorphisms and response to fluorouracil-based treatment in advanced colorectal cancer patients

Methylenetetrahydrofolate reductase (MTHFR) controls intracellular CH2FH4 concentrations (required for optimal fluoropyrimidine efficacy) by irreversibly converting CH2FH4 into 5-methyltetrahydrofolate. MTHFR 677C>T and 1298A>C polymorphisms are linked to altered enzyme activity. Thus, mutated MTHFR tumours should, in theory, be more sensitive to 5-fluorouracil (5FU) than wild-type tumours. MTHFR polymorphisms in position 677 and 1298 were analysed in 98 colorectal cancer patients with unresectable liver metastases (57 men, 41 women, mean age 64 years) receiving 5FU-folinic acid. 677C>T and 1298A>C genotypes were determined simultaneously by melting curve analyses on liver metastases. 677C>T genotype distribution was 46.9% wt/wt, 34.7% wt/mut and 18.4% mut/mut; that of 1298A>C was 52.0% wt/wt, 35.7% wt/mut and 12.3% mut/mut. The response rate was not related to 1298A>C genotype but was significantly linked to 677C>T genotype (response rate: 40%, 21% and 56% in wt/wt, wt/mut and mut/mut, respectively; P = 0.040), with an increased response rate in mut/mut tumours relative to wt/wt (odds ratio = 1.88). Thymidylate synthase activity measured in metastases was a significant predictor of 5FU responsiveness and the addition of the 677C>T genotype improved model prediction. MTHFR 1298A>C polymorphism was significantly linked to specific survival, with homozygous mutated patients having the worst prognosis (P = 0.009, relative risk = 2.48 in mut/mut versus wt/wt). MTHFR 1298A>C genotype remained a significant predictor in a multivariate analysis including metastasis characteristics. The results suggest that MTHFR genotypes are relevant and independent factors of patient outcome in 5FU-based treatment of advanced colorectal cancer.     

亚甲基四氢叶酸还原酶C677T与A1298C基因多态性在卡培他滨治疗中晚期结直肠癌患者的临床意义

目的 探讨亚甲基四氢叶酸还原酶（MTHFR）C677T与A1298C基因多态性在卡培他滨治疗中晚期结直肠癌（CRC）患者的安全性及有效性,为临床诊治CRC提供理论依据。方法 收集经病理诊断确诊的中晚期结直肠癌患者50例,用实时荧光定量PCR仪进行MTHFR C677T与A1298C基因多态性检测,观察不同基因型之间安全性及有效性的差异。结果 MTHFR C677T的CC、CT、TT基因型频率分别为46%、40%、14%,TT基因型恶心呕吐的发生率及有效率高于CC与CT基因型,差别具有统计学意义（P<0.05）。MTHFR A1298C的AA、AC、CC基因型频率分别为60%、34%、6%,CC基因型腹泻发生率高于AA与AC基因型,差别具有统计学意义（P<0.05）,MTHFR A1298 C中各基因型有效率差异无统计学意义。结论 MTHFR C677T与MTHFR A1298C基因多态性在卡培他滨治疗CRC患者具有较好的临床意义,但MTHFR A1298C与药物治疗有效率无关。     

Methylenetetrahydrofolate reductase (MTHFR) variants and fluorouracil-based treatments in colorectal cancer

5-fluorouracil (5FU)-based treatments remain the main chemotherapy for colorectal cancer. Optimal cytotoxicity of fluoropyrimidines requires elevated CH(2)FH(4) tumoral concentrations, controlled by the methylenetetrahydrofolate reductase (MTHFR) enzyme, which irreversibly converts CH(2)FH(4) into 5-methyltetrahydrofolate. The MTHFR gene is subject to several polymorphisms, of which the 677C>T and 1298A>C SNPs are the two most commonly linked with altered enzyme activity. Since a drop in MTHFR enzymatic activity may theoretically favor an increase in intracellular CH(2)FH(4) concentrations, it can be hypothesized that tumors exhibiting the rare MTHFR variants may be more sensitive to 5FU cytotoxicity. Accordingly, experimental data have shown that rare MTHFR variants in position 677 and 1298 are more sensitive to 5FU. However, results of clinical data do not concord regarding the influence of MTHFR genotype on tumoral CH(2)FH(4) concentration, 5FU responsiveness, patient survival and 5FU-related toxicity. These discrepancies may result from the interpatient variability arising from the individual folate status, as well as from the limited role of fluoropyrimidines in the current chemotherapy regimen administered in colorectal cancer.     

亚甲基四氢叶酸还原酶单核苷酸多态性与类风湿关节炎的相关性研究

目的检测我国南方汉族健康人群及类风湿关节炎（RA）患者亚甲基四氢叶酸还原酶（MTHFR）677C／T和1298A／C两个单核苷酸多态性的频率及遗传连锁关系,并分析两个单核苷酸多态性（SNPs）位点与RA的关系。方法研究对象共187人,其中健康对照组101人,RA患者86人,应用聚合酶链式反应-限制性片段长度多态性（PCR-RFLP）技术检测基因型和等位基因的分布频率,群体数理遗传学方法分析MTH-FRSNP的遗传平衡吻合度和相互间连锁不平衡关系。结果经Hardy-Weinberg检验,所研究的2个SNP位点各基因频率达到遗传平衡。677CC、CT、TT基因型在RA组中分别占36．0％、51．2％和12．8％,在对照组中分别为42．6％、44．6％和12．9％,两组频率分布无显著性差异（P〉0．05）。1298AA、AC、CC基因型在RA组中分别占60．5％、32．6％和7．0％,在对照组中分别为49．5％、46．5％和4．0％,分布无显著性差异（P〉0．05）。少见型677T等位基因在RA组和对照组分别为38．4％和35．1％,1298C在两组中分别为23．3％和27．2％,比较均未见差异。677C／T与1298A／C为强连锁不平衡关系。结论MTHFR677C／T和1298A／C与RA无明确关联。该人群中677C／T与1298A／C为强连锁不平衡关系。     

MTHFR基因多态性与ALL患儿MTX血药浓度及严重毒副反应的相关性研究

目的：在儿童急性淋巴细胞白血病（ALL）患者中,探讨亚甲基四氢叶酸还原酶（MTHFR C677T和A1298C）基因多态性与甲氨蝶呤（MTX）化疗后44 h血药浓度和严重毒副反应间的相关性。方法：收集77例ALL患儿临床资料,监测MTX输注后44 h的血药浓度并进行MTHFR基因分型;分析MTHFR C677T基因型和A1298C基因型与MTX 44 h血药浓度及严重毒副反应间的相关性。结果：MTHFR C677T、A1298C各基因型与MTX 44 h血药浓度间均无统计学差异（P>0.05）。未发现MTHFR C677T基因多态性与MTX化疗后严重毒副反应间存在相关性（P>0.05）。MTHFR A1298C杂合突变型（AC）相比野生型（AA）,发生血红蛋白减少的风险增加（P=0.002）,未发现其他严重毒副反应与MTHFR A1298C基因多态性间存在相关性（P>0.05）。结论：MTHFR A1298C基因多态性可能与ALL患儿MTX化疗后血红蛋白减少有一定相关性。     

Pharmacogenetic relevance of MTHFR polymorphisms

The 5,10-methylenetetrahydrofolate reductase (MTHFR) is a key enzyme for intracellular folate homeostasis and metabolism. Two common MTHFR polymorphisms, C677T and A1298C, which lead to an altered amino acid sequence, have been associated with a decreased enzyme activity and susceptibility to cancer suggesting that these genetic variants may modulate the risk of several malignancies. C667T, and to a lesser extent A1298C polymorphisms, are also reported to influence the cytotoxic effect of fluoropyrimidines and antifolates providing support for their pharmacogenetic role in predicting the efficacy and the toxicity in cancer and rheumatoid arthritis patients. A combined polymorphisms and haplotype analysis may result in a more effective approach than a single polymorphism one. Moreover gene-nutrient/environmental and gene-racial/ethnic interactions have been shown to affect the impact of these MTHFR genetic variants. Further well-designed studies are needed to clarify the role of MTHFR polymorphisms to derive dose adjustment recommendations on the basis of the patient's genotype.     

MTHFR基因多态性与下肢DVT的相关性研究

目的探讨N5,N10-亚甲基四氢叶酸还原酶(Methylenetetrahydrofolatereductase,MTHFR)基因多态性与我国东北地区人群下肢深静脉血栓形成(Deepvenousthrombosis,DVT)的关系。方法采用PCR-RFLP检测73例DVT患者和109名健康对照者MTHFRC677T、A1298C突变,计算患者组与对照组的基因型频率、等位基因频率以及突变与DVT的相关性。结果患者组677TT、677CT基因型频率和T等位基因频率分别为38.4%、49.3%和63%,明显高于对照组(分别为15.6%、46.8%和39%。χ2=19.393,P<0.01;χ2=20.200,P<0.01)。677TT和677CT基因型的个体比677CC基因型的个体发生DVT的相对危险分别约高7或3倍(ORTT=7.503,95%可信区间为2.931～19.207;ORTC=3.215,95%CI为1.391～7.434)。患者组与对照组MTHFR1298各基因型和等位基因分布无显著性差异(χ2=3.533,P>0.05;χ2=0.100,P>0.05),但1298CC677CC基因型的个体比1298AA、677CC基因型的个体发生DVT的相对危险约高16倍(OR=16.500,95%CI为1.353～201.290)。结论MTHFR基因C677T和A1298C突变可能为我国东北地区人群下肢DVT的危险因素。     

677C > T and 1298A > C MTHFR polymorphisms affect arechin treatment outcome in rheumatoid arthritis

Despite the availability of several new agents for the treatment of rheumatoid arthritis (RA), arechin (hydroxychloroquine) remains the mainstay because of both cost-effectiveness and experience with its use. However, there is considerable variation in response to this drug, with toxicity limiting treatment in some patients. Methylenetetrahydrofolate reductase (MTHFR) is involved in the folate metabolism and has been shown to be polymorphic what affects the enzyme activity. To examine the association between 677C > T and 1298A > C MTHFR polymorphisms and arechin efficacy in the treatment of RA, a total of 50 RA patients, treated with arechin were analyzed. In univariate regression analysis model, MTHF R 677T allele was associated with significantly higher frequency of remission, whereas 1298C allele carriers showed a tendency to higher remission rate. In univariate regression analysis model, the presence of MTHFR 677T allele was associated with 2.3-fold higher frequency of remission. Multivariate regression analysis taking into the account the combined effect of MTHFR 677T and 1298C alleles revealed that both alleles were independent factors associated with increased frequency of remission. The results of our study suggest that 677T and 1298C alleles are independent factors associated with increased frequency of remission and the evaluation of C677C > T and A1298A> C MTHFR polymorphisms may be a useful tool to predict arechin treatment outcome in RA patients.     

叶酸代谢酶MTHFR、MTRR基因多态性与原因不明复发性流产的关系

目的 探讨叶酸代谢相关酶亚甲基四氢叶酸还原酶（MTHFR）、甲硫氨酸合酶还原酶（MTRR）基因多态性与原因不明复发性流产（URSA）之间的关系。 方法 采用病例对照的研究方法, 选取天津医科大学总医院和天津市妇女儿童保健中心 2013 年 1 月 1 日—2015 年 3 月 1 日因 URSA 就诊的非妊娠妇女 244 例（URSA 组）和健康非妊娠妇女 116 例（ 对照组）。 获取口腔黏膜上皮细胞, 使用荧光定量 PCR 检测 MTHFR 基因 C677T、A1298C 位点和 MTRR 基因 A66G 位点的单核苷酸多态性（SNP）, 同时测定 MTHFR 酶活性及红细胞叶酸、血浆叶酸、血浆同型半胱氨酸水平, 分析叶酸代谢相关酶 MTHFR、MTRR 基因多态性与 URSA 之间的关系。 结果 URSA 组 MTHFR C677T 位点 TT 基因型频率高于对照组, CT 基因型频率低于对照组（P＜ 0.05）。 2 组间 MTHFR A1298C、MTRR A66G 基因型频率差异无统计学意义。 URSA 组 MTHFR 酶活性、红细胞叶酸、血浆叶酸水平低于对照组, 同型半胱氨酸水平高于对照组（P＜ 0.05）; URSA 组中＜ 35 岁、≥35 岁患者血浆叶酸、红细胞叶酸、同型半胱氨酸水平差异无统计学意义。结论 MTHFR C677T 基因多态性与 URSA 有一定关系。     

Biological and clinical implications of the MTHFR C677T polymorphism

The enzyme methylenetetrahydrofolate reductase (MTHFR) directs folate species either to DNA synthesis or to homocysteine (Hcy) remethylation. The common MTHFR C677T polymorphism affects the activity of the enzyme and hence folate distribution. Under conditions of impaired folate status, the homozygous TT genotype has been regarded as harmful because it is associated with a high concentration of plasma total Hcy, increased risk of neural tube defects and colorectal neoplasias, and can also predispose individuals to adverse effects from drugs with antifolate effects. The MTHFR C677T polymorphism shows no consistent correlation with cardiovascular risk and longevity but, in combination with positive folate balance, the TT genotype is associated with decreased risk of colorectal neoplasias. Because of the high prevalence of this polymorphism in most populations, the TT variant might represent an ancestral genetic adaptation to living constraints (tissue injury or unbalanced vitamin intake) that has become a determinant of disease profiles in modern times.     

基因多态性对宜昌地区类风湿关节炎患者甲氨蝶呤疗效的影响

目的 探讨甲基四氢叶酸还原酶(MTHFR)和ATP结合盒转运蛋白1(ABCB1)等位基因在宜昌地区类风湿关节炎(RA)患者中分布情况,及其与甲氨蝶呤(MTX)治疗效果的相关性.方法 收集整理2016年1月-2019年6月宜昌某三甲医院基因检测室进行MTHFR C677T、MTHFR A1298C、ABCB1 C3435...     

Homocysteine determinants and the evidence to what extent homocysteine determines the risk of coronary heart disease

Cardiovascular diseases (CVD), especially coronary heart disease (CHD), are the most important causes of death in industrialized countries. Increased concentrations of total plasma homocysteine (tHcy) have been associated with an increased risk of CHD. Assuming that this relation is causal, a lower tHcy concentration will reduce the occurrence and recurrence of CHD. Therefore, it is important to know which factors determine the tHcy concentration. In the general population, the most important modifiable determinants of tHcy are folate intake and coffee consumption. Smoking and alcohol consumption are also associated with the tHcy concentration, but more research is necessary to elucidate whether these relations are not originating from residual confounding due to other lifestyle factors. The most important nonmodifiable determinant is the 677 C>T polymorphism in the gene that encodes methylenetetrahydrofolate reductase (MTHFR), a regulating enzyme in homocysteine metabolism. Especially subjects with the homozygous form of this polymorphism (i.e., 677TT genotype) and a low folate status have elevated tHcy concentrations. Specific clinical conditions like the use of antiepileptic drugs or methotrexate, renal failure, cancer, rheumatoid arthritis, and hypothyroidism may lead to elevated tHcy concentrations. The available epidemiological evidence indicates that an increased tHcy concentration is not an important risk factor for CHD in healthy subjects. However, prospective studies, which included subjects at high risk of CHD, and secondary prevention trials with intermediary endpoints consistently show that elevations in the tHcy concentration may be an important risk factor in these subjects for a (recurrent) CHD event. The induction of vascular endothelial dysfunction by homocysteine may underlie this increased risk. Ongoing intervention trials will indicate whether homocysteine-lowering through vitamin supplementation, prevents CHD in the treatment groups.     

The MTHFR C677T polymorphism is associated with depressive episodes in patients from Northern Ireland

Low plasma folate and its derivatives have been linked with depressive disorders in studies dating back over 30 years. A thermolabile variant (677C>T) of the enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR) is associated with low serum folate. The present study aimed to explore whether the thermolabile variant of MTHFR is associated with a vulnerability to depressive episodes. MTHFR C677T genotype frequencies in a cohort of patients (mean age 48 years) with depressive disorder (n = 100) were compared with those in age- and sex-matched controls. Serum levels of folate, homocysteine and vitamin B(12) were also compared between groups. The thermolabile variant of MTHFR was significantly more common in the group with a history of depressive disorder (P= 0.03). Serum levels of folate, homocysteine and vitamin B(12) did not differ significantly between groups. A MTHFR C677T genotype is associated with increased risk of depressive episodes in this homogenous patient population.     

Review and pooled analysis of studies on MTHFR C677T polymorphism and esophageal cancer

Esophageal cancer has been associated with tobacco and alcohol consumption, gastric reflux, exposure to nitrosamines from food or other environmental sources, and diets lacking folate. Susceptibility to esophageal cancer may be modified by functional polymorphisms in genes along the folate metabolic pathway, such as methylenetetrahydrofolate reductase (MTHFR). The C677T polymorphism is the most common functional variant, leading to a reduction in enzyme activity. We report a pooled analysis of 5 studies on the association of MTHFR C677T polymorphism and esophageal cancer, including 725 cases and 1531 controls. A significant association between the MTHFR 677 TT genotype and esophageal cancer was observed (OR=2.63, 95% CI: 1.75-3.94), although there was significant heterogeneity between studies. A sensitivity analysis excluded one study; the association between TT genotype and esophageal cancer was still present, although of reduced magnitude (OR=1.57, 95% CI: 0.96-2.56). A significant interaction between smoking and TT genotype on esophageal cancer risk was observed, while no interaction was observed between alcohol consumption and genotype.     

N5,N10-亚甲基四氢叶酸还原酶基因多态性与青年脑梗死的关系

目的 研究N5,N10 -亚甲基四氢叶酸还原酶(MTHFR)基因多态性与青年脑梗死的关系.方法 将67例青年脑梗死患者作为病例组,同期71例健康体检者作为对照组,用聚合酶链反应-限制性内切酶片段长度多态性分析(PCR-RFLP)的方法来观察MTHFR 677和1298位点基因型.结果 MTHFR 677位点基因型病例组中TT型为20例,占29.8％;CT型32例,占47.8％;CC型15例,占22.4％;T等位基因频率为53.7％.对照组中TT型30例,占42.2％;CT型34例,占47.9％;CC型7例,占9.9％;T等位基因频率为66.2％.对照组中TT型及T等位基因频率明显高于病例组,2组差异有统计学意义(P＜0.05).MTHFR1298位点基因型病例组中AC型29例,占43.3％;AA型38例,占56.7％;C等位基因频率为21.6％.对照组中AC型14例,占19.7％,AA型57例,占80.3％,C等位基因为9.9％,病例组中AC型及C等位基因频率明显高于对照组,2组差异有统计学意义(P＜0.05).结论 本组人群中MTHFR基因677及1298位点多态性与青年脑梗死都有相关性.     

高同型半胱氨酸血症及MTHFR基因与中青年脑梗死的研究

目的 :探讨高同型半胱氨酸血症 (HHC)及N5,N10-亚甲四氢叶酸还原酶(MTHFR)基因型与中青年脑梗死的关系。方法 :采用高压液相色谱法及PCR -RFLP技术测定80例脑梗死患者和40例正常对照者的血浆总同型半胱氨酸水平 (tHcy)和MTHFR基因多态性。结果 :患者组中MTHFR基因T/T纯合型频率为33.75 % ,T等位基因频率为58.75 % ,显著高于对照组的20 %和36.25 % (P<0.05) ;患者组血浆tHcy均值为22.70μmol/L ,对照组仅为13.19μmol/L ,患者组HHC31例 ,对照组仅为2例 ,2组差别有统计学意义,且2组T/T型者血浆tHcy水平高于T/C型和C/C型者。结论 :MTHFR基因突变可能是脑梗死发生的一个遗传易感因素 ,tHcy可能与血脂血糖一样是脑卒中发病的一个独立危险因素     

结直肠癌患者肿瘤组织与外周血中MTHFR C677T的多态性及相关性研究

目的 探索外周血代替肿瘤组织进行MTHFR C677T基因多态性检测的可行性.方法 选取首诊为结直肠癌且行根治性手术的患者26例,术前未接受任何化学治疗,应用聚合酶链反应-限制性内切片段长度多态性（PCR-RFLP）方法检测MTHFR C677T的基因多态性,比较外周血及肿瘤组织中相关基因型的一致性.结果 26例结直肠癌患者的肿瘤组织及外周血中MTHFR 677CT基因型、TT基因型、CC基因型一致的病例数分别为7、7、4例.肿瘤组织和外周血中MTHFR C677T的基因型一致率为69.2%.结论 外周血中MTHFR C677T的基因多态性可以反映肿瘤组织中相关基因型的突变.     

Interactions between the single nucleotide polymorphisms in the homocysteine pathway (MTHFR 677C>T, MTHFR 1298 A>C, and CBSins) and the efficacy of HMG-CoA reductase inhibitors in preventing cardiovascular disease in high-risk patients of hypertension: the GenHAT study

BACKGROUND: High homocysteine blood concentrations predispose to coronary artery disease and statins influence homocysteine levels. AIM: To study whether genes that regulate homocysteine metabolism interact with statins to modify the risk of coronary heart disease (CHD) and other cardiovascular outcomes. METHODS: The Genetics of Hypertension Associated Treatment is an ancillary study of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). The genotyped population in the Lipid-Lowering Trial of Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial included 9624 participants randomly assigned to pravastatin or to usual care. The efficacy of pravastatin in reducing risk of all-cause mortality and CHD was compared among genotype strata (MTHFR 677 CC, CT, and TT, MTHFR 1298 AA, AC, and CC, CBSins DD and I) by examining an interaction term in a proportional hazards model. RESULTS: No evidence existed of a pharmacogenetic effect on statins with the MTHFR 1298 A>C genotype for CHD risk. However, in persons with the CC variant for the MTHFR 677 C>T genotype, a significantly protective effect against CHD [0.71 (95% CI 0.58-0.87)] was shown, although in the CT [1.25 (95% CI 0.97-1.61)] and TT groups [0.80 (95% CI 0.50-1.28)] there were no such effects (interaction hazard ratio P=0.004). The CBSins, I+ variant was associated with a significantly reduced risk for CHD among those on statin treatment [0.58 (95% CI 0.44-0.78)] whereas the DD genotype showed no effect of statin therapy [1.01 (95% CI 0.84-1.20; P=0.002 for interaction]. For the endpoint all-cause mortality, no significant differences in efficacy were noted. CONCLUSION: Polymorphisms in genes in the homocysteine pathway (MTHFR 677 C>T and CBSins) appear to modify the efficacy of pravastatin in reducing risk of cardiovascular events.     

MTHFR基因多态性与冠心病的关系

目的研究天津地区人群N5,N10-亚甲基四氢叶酸还原酶(MTHFR)基因C 677 T多态性与冠心病的关系.方法应用聚合酶链反应(PCR)技术和限制性酶切片段长度多态性(RFLP)分析技术检测50例冠心病患者(冠心病组)和50例正常人(对照组)MTHFR基因C 677 T多态性,应用高效液相色谱法测定血浆同型半胱氨酸(Hcy)水平,采用125Ⅰ标记放免法测定血清叶酸浓度.结果(1)冠心病组与对照组MTHFR基因频率分布不同(P＜0 05),对照组CC型、TC型、TT型基因频率分别为52.0%,28.0%,20.0%;冠心病组分别为26.0%,44.0%,30.0%.冠心病组T等位基因频率为52.0%,C等位基因频率为48.0%,与对照组比较有显著性差异(P＜0.05).(2)两组的TT基因型者血浆Hcy浓度均明显高于CC和TC基因型者(P＜0.05),而后两者间无显著性差异(P＞0.05).(3)冠心病组Hcy浓度高于对照组(P＜0.05).两组叶酸水平无显著性差异(P＞0.05),血浆Hcy浓度与叶酸水平均呈显著负相关(r分别为-0.617和-0.588,P＜0.05).结论MTHFR基因C 677 T点突变与冠心病发病密切相关,MTHFR基因纯合突变是引起高Hcy血症的一个重要的遗传因素.     

Genetic polymorphisms in metabolic and cellular transport pathway of methotrexate impact clinical outcome of methotrexate monotherapy in Japanese patients with rheumatoid arthritis

The aim of this study was to investigate the impact of genetic polymorphisms in the metabolic and cellular transport pathway of methotrexate (MTX) on the clinical outcome of MTX monotherapy in Japanese rheumatoid arthritis (RA) patients. Fifty-five patients were treated with MTX monotherapy at a dose of 4-10 mg/week. The total concentration of MTX-polyglutamates (MTX-PGs) was measured at steady-state in red blood cells (RBCs) by high performance liquid chromatography. The genotype at 16 polymorphic sites in 11 genes (ABCB1, ABCG2, ABCC2, RFC1, PCFT, SLCO1B1, MTHFR, GGH, ATIC, MTR, and MTRR) was analyzed. No significant association between the total concentration of MTX-PGs in RBCs and clinical outcome was found. However, patients with the ABCB1 3435TT genotype had a significantly lower mean disease activity score (DAS) 28 than did patients with the ABCB1 3435CC genotype (p = 0.02). Similarly, patients with the ABCB1 2677AA/AT/TT genotypes had a significantly lower mean DAS28 than did patients with the ABCB1 2677GG/GA/GT genotypes (p = 0.04). The patients with the MTHFR 1298AA genotype had a significantly lower mean DAS28 than those with the MTHFR 1298AC/CC genotypes (p = 0.04). In conclusion, the ABCB1 3435C>T, ABCB1 2677G>A/T, and MTHFR 1298A>C polymorphisms influenced the efficacy of MTX monotherapy.