ABCB1基因多态性对肾移植受者环孢素血浓度的影响

目的:研究肾移植术后患者ABCB1基因多态性对环孢素（CsA）血浓度的影响。方法:采用PCR-RFLP（聚合酶链反应-限制性片段长度多态性）方法对339名服用CsA的肾移植患者进行ABCB1基因1236C>T、2677G>T/A和3435C>T多态性检测,荧光偏振免疫法检测肾移植患者CsA血浓度。结果:在339名肾移植患者中,ABCB1基因1236C>T、2677G>T/A和3435C>T突变等位基因频率分别为64.25%、51.54%和35.75%。ABCB1 1236C>T基因多态性检测显示,在移植术后1年,CC基因型个体的CsA血谷浓度明显高于CT和TT基因型个体（P<0.05）。2677G>T/A基因多态性检测提示,在移植术后7d,杂合子GA+GT基因型携带者的C₀高于GG和AA+TT+AT基因型携带者（P<0.05）。3435C>T基因多态性检测表明:在移植术后3个月,突变纯合子TT基因型携带者的C₀低于CC和CT基因型携带者（P<0.05）。其余各时间点,上述3种基因多态性对CsA血谷浓度无明显影响（P>0.05）。结论:ABCB1基因1236C>T、2677G>T/A和3435C>T多态性对极少数时间点的CsA浓度有影响,但对绝大多数时间点的环孢素浓度无影响。     

CYP2C19*3基因多态性对癫痫患者奥卡西平活性代谢产物MHD浓度的影响

目的：分析CYP2C19*3基因多态性与癫痫患者奥卡西平（oxcarbazepine，OXC）活性代谢产物10，11-二氢-10-羟基卡马西平（monohydroxycarbazepine，MHD）血药浓度的相关性。方法：纳入120例OXC单药治疗1个月以上且症状控制良好的癫痫患者，采集清晨服药前空腹血，采用高效液相色谱法测定MHD稳态谷浓度。通过PCR和sanger测序判定患者CYP2C19*3基因型。结果：120例癫痫患者快代谢患者64例，MHD血浆浓度为（18.17±7.34）μg·mL^-1；中代谢型患者36例，MHD血浆浓度为（19.31±9.17）μg·mL^-1；慢代谢型患者20例，MHD血浆浓度为（25.79±7.51）μg·mL^-1，3种基因型的MHD浓度有显著性差异（F=7.077，P=0.0013）。多因素分析显示，日剂量作为影响血药浓度的重要指标呈现出显著相关性（P<0.05）。结论：CYP2C19*3基因多态性影响MHD血药浓度，并且日剂量越高，MHD血药浓度越大，两者成显著正相关，临床应进行血药浓度监测。     

儿童急性淋巴细胞白血病中ABCB1C3435T位点基因多态性对大剂量甲氨蝶呤血药浓度及不良反应的影响

目的研究急性淋巴细胞白血病(ALL)儿童的ABCB1 C3435T位点(rs1045642)基因多态性与大剂量甲氨蝶呤(HD-MTX)化学治疗后血浆中甲氨蝶呤血药浓度和不良反应的相关性。方法选取2015年8月至2019年6月于我院小儿血液内科住院治疗的132例ALL患儿,在接受HD-MTX治疗前应用聚合酶链反应(PCR)-芯片杂交技术测定ABCB1基因3435位点的基因型。在HD-MTX开始后48 h采集患儿外周血,应用荧光偏振免疫法测定血浆甲氨蝶呤浓度,同时观察化疗后的不良反应,分析ABCB1基因多态性与HD-MTX治疗后MTX血药浓度和不良反应之间的关系。结果ABCB1 C3435T位点基因多态性与HD-MTX化疗开始后48 h的MTX血药浓度之间有相关性(P<0.05),突变型TT型48 h的MTX血药浓度更高。而在ABCB1 C3435T位点基因多态性与HD-MTX化疗所产生的各种不良反应方面,未发现相关性(P>0.05)。结论ABCB1 C3435T位点基因多态性与ALL患儿大剂量甲氨蝶呤化疗后MTX的血药浓度有关,而与不良反应(骨髓抑制、肾功能损害)无关。     

217例次癫痫患儿血清奥卡西平代谢物浓度监测分析

目的 对血清奥卡西平活性代谢物(MHD)浓度监测结果 进行分析. 方法 采用高效液相色谱(HPLC)法测定血清MHD浓度,色谱柱为Inertsil ODS-3柱(4.6 mm×250 mm,5 μm),流动相为甲醇:水(45:55),流速1 mL.min^-1,检测波长225 nm. 结果 在217例次癫痫患儿MHD的血药浓度测定结果 中,有65.0%患儿血药浓度在治疗窗内,35.0%血药浓度偏低. 结论 儿童癫痫患者服用奥卡西平后,血清MHD浓度个体差异较大,及时监测血药浓度有助于及时调整用药剂量,促进奥卡西平个体化给药方案的实施.     

ABCB1基因多态性对卡马西平血药浓度的影响

目的:探讨ABCB1基因多态性对卡马西平血药浓度的影响。方法:采用荧光偏振免疫法(FPIA)测定275例口服卡马西平癫痫患者的血药浓度,聚合酶链式反应-限制性片段长度多态性方法(PCR-RFLP)或直接测序法检测ABCB1多态性位点C1236T、G2677T/A和C3435T的基因型。单因素方差分析计算各SNP位点不同基因型对应的卡马西平血药浓度是否有差异。结果:G2677T/A不同基因型对应的调整后血药浓度均值之间差别有显著性,TT基因型对应的调整后血药浓度显著高于GG型(P=0.001)。C1236T、C3435T各基因型对应的调整后血药浓度均值差别无统计学意义(P>0.05)。结论:ABCB1基因SNP位点G2677T/A的基因多态性对口服卡马西平癫痫患者的血药浓度有影响,提示TT基因型的患者可适当减少药物使用剂量。     

ABCB1、CYP2B6基因多态性对丙泊酚血药浓度的影响

摘要：目的:探讨药物转运体ABCB1 C3435T与药物代谢酶CYP2B6 G516T基因多态性对丙泊酚血药浓度的影响,为丙泊酚临床个体化给药提供实验室数据。方法:采用荧光染色原位杂交法（FISH）,进行ABCB1 C3435T和CYP2B6 G516T基因多态性检测,用高效液相-荧光法检测血药浓度。根据不同基因型患者使用丙泊酚麻醉后30,60 min给药总量,比较基因多态性与丙泊酚标准化血药浓度的关系。结果:丙泊酚持续给药30 min时,ABCB1 C3435T三种基因型患者给药总量和标准血药浓度比较,差异无统计学意义（P>0.05）;丙泊酚持续给药60 min时,ABCB1不同基因型患者给药总量有明显差异（P<0.05）,ABCB1 C3435T野生纯合子CC基因型患者给药总量高于变异型（CT/TT）患者。给药60 min时,4组患者给药总量差异有统计学意义（P<0.05）。不同CYP2B6 G516T基因型患者在丙泊酚持续给药30 min和60 min时,给药总量和标准血药浓度无相关性。结论:ABCB1 C3435T基因多态性对丙泊酚血药浓度有影响,野生型患者为达到相同的血药浓度需要提高给药剂量。     

ABCB1 3435C>T基因多态性对急性淋巴细胞白血病患儿大剂量甲氨蝶呤血药浓度及不良反应的影响

摘 要 目的：研究急性淋巴细胞白血病（ALL）患儿多药耐药基因1（ABCB1）基因多态性与使用大剂量甲氨蝶呤（MTX）化疗期间的血药浓度及不良反应的关系。方法: 70例ALL患儿外周血,提取DNA,采用PCR技术和直接测序的方法分析ABCB1基因的基因型;采用酶放大免疫法（EMIT）测定MTX给药后48h的血药浓度;2.华中科技大学同济医学院同济医院药学部,统计不良反应相关信息。分析ABCB1基因多态性与MTX血药浓度及不良反应的关系。结果: ABCB1 C3435T位点存在多态性,ABCB1 C3435T位点患儿CC、CT和TT基因型的分布频率分别为31.43%,47.14%,21.43%。ABCB1 C3435T位点各基因型MTX 48h C/D值由低到高依次为CC型患儿、CT型患儿、TT型患儿,其中TT型与CC型之间差异具有统计学意义(P＜0.05)。ABCB1 C3435T位点不同基因型患者中,口腔黏膜损害、肝脏损害发生率差异有统计学意义（P＜0.05）。结论:ABCB1 C3435T位点基因多态性与ALL患儿大剂量MTX化疗后的血药浓度及不良反应（口腔黏膜炎、肝脏损害）有关。     

年龄性别对癫痫患儿奥卡西平活性代谢物血药浓度的影响分析

目的:探讨年龄及性别因素对癫痫患儿奥卡西平代谢产物血药浓度的影响.方法:采用高效液相色谱法(HPLC)对217例服用奥卡西平的儿童癫痫患儿进行奥卡西平活性代谢产物(MHD)血清稳态质量浓度测定,分析其血清浓度与年龄、性别的关系.结果:在推荐剂量8～46 mg/(kg-d)范围内,服用奥卡西平的患儿血清MHD质量浓度随着年龄增长有升高趋势,但差异无统计学意义(P＞0.05);相同条件下,不同性别组患儿血清MHD质量浓度差异无统计学意义(P＞0.05).结论:在推荐剂量范围内,奥卡西平活性代谢产物的血清质量浓度与性别无相关性,虽随年龄增加而升高,但差异无统计学意义.因此选用奥卡西平治疗癫痫患儿时应定期进行血药浓度监测,及时调整用药剂量,尽量实现个体化用药.     

新型抗癫痫药物奥卡西平基因多态性研究进展

奥卡西平是癫痫部分性发作和全面强直阵挛性发作的首选药物之一,是卡马西平的一种10-酮类衍生物,其耐受性好且不良反应少。然而,临床研究表明奥卡西平在相同群体的不同个体和不同群体之间呈现出显著差异,其中遗传因素起到重要作用。本文通过收集近年来国内外有关奥卡西平代谢酶、转运体、药效靶蛋白以及不良反应方面有关基因多态性的文献报道,进一步明确其对奥卡西平血药浓度、疗效及不良反应的影响,为临床个体化治疗提供参考。     

ABCB1基因单核苷酸多态性对伏立康唑血药浓度的影响1例并文献复习

目的 了解腺苷三磷酸结合盒转运体B1(ABCB1)基因单核苷酸多态性对伏立康唑血药浓度的影响。方法 对我院1例急性淋巴细胞性白血病合并侵袭性肺曲霉病的患者在给予伏立康唑治疗期间，ABCB1基因单核苷酸多态性对伏立康唑体内代谢的影响进行分析，并以“伏立康唑”、“腺苷三磷酸结合盒转运体B1”或“ABCB1”为主题词检索万方、维普和中国知网数据库，以“Voriconazole”、“ABCB1”为主题词检索Pubmed数据库，检索国内外报道的ABCB1(c.3435C>T,rs1045642)单核苷酸多态性影响伏立康唑体内代谢的病例，筛选并总结分析病例资料。结果 本院报道的病例，当伏立康唑维持剂量为200 mg(4.26 mg·kg^-1)静滴时，初始谷浓度为0.25μg·mL^-1。经多次治疗药物监测(Therapeutic drug monitoring, TDM),同时进行ABCB1及CYP2C19基因测序，将维持剂量提高到300 mg(6.38 mg·kg^-1)静滴或350 mg(7.45 mg·kg^-1     

Effects of UGT1A1, CYP3A5 and ABCB1 Genetic Variants on Pharmacokinetics of Antihistamine Drug Mizolastine in Chinese Healthy Volunteers

Mizolastine is a selective histamine H1 receptor antagonist for chronic urticaria or allergic rhinitis. We investigated whether the variant genotypes of metabolic enzymes UGT1A1, CYP3A5 and transporter ABCB1 influence pharmacokinetic phenotype of substrate mizolastine in Chinese volunteers. Genotyping of single nucleotide polymorphisms in UGT1A1*6 (G211A), CYP3A5*3 (A6986G) and ABCB1 (C3435T) was determined by the pyrosequencing method. After a single oral dose of 10 mg mizolastine, the plasma concentrations were measured using validated high‐performance liquid chromatography in 24 Chinese healthy volunteers. The results showed that the distributions of wild‐type homozygotes and variant allele carriers (the sum of variant heterozygotes and variant homozygotes) were as follows: 17 cases (70.8%) versus seven cases (29.2%) in UGT1A1*6 genotypes, five cases (20.8%) versus 19 cases (79.2%) in CYP3A5*3 genotypes and seven cases (29.2%) versus 17 cases (70.8%) in ABCB1 3435T genotypes, respectively. There were no significant differences in pharmacokinetic parameters of mizolastine between the variant allele UGT1A1*6, CYP3A5*3 and ABCB1 3435T carriers and the wild‐type homozygotes, and the ratios were as follows: C_max was 101.03%, 86.02% and 105.78%; T_max was 162.35%, 98.98% and 144.90%; AUC_0–28 was 113.04%, 77.35% and 112.71%; and t_1/2 was 95.77%, 72.40% and 100.97%, respectively. In conclusion, these results suggested that the UGT1A1, CYP3A5 and ABCB1 genetic polymorphisms might be not contributed to the interindividual variation of mizolastine pharmacokinetic phenotype in the Chinese population.     

Population pharmacokinetic analysis of risperidone and 9-hydroxyrisperidone with genetic polymorphisms of CYP2D6 and ABCB1

This study estimated the population pharmacokinetics of risperidone and its active metabolite, 9-hydroxyrisperidone, according to genetic polymorphisms in the metabolizing enzyme (CYP2D6) and transporter (ABCB1) genes in healthy subjects. Eighty healthy subjects who received a single oral dose of 2?mg risperidone participated in this study. However, eight subjects with rare genotype variants in CYP2D6 alleles were excluded from the final model built in this study. We conducted the population pharmacokinetic analysis of risperidone and 9-hydroxyrisperidone using a nonlinear mixed effects modeling (NONMEM) method and explored the possible influence of genetic polymorphisms in CYP2D6 alleles and ABCB1 (2677G>T/A and 3435C>T) on the population pharmacokinetics of risperidone and 9-hydroxyrisperidone. A two-compartment model with a first-order absorption and lag time fitted well to serum concentration-time curve for risperidone. 9-hydroxyrisperidone was well described by a one-compartment model as an extension of the parent drug (risperidone) model with first-order elimination and absorption partially from the depot. Significant covariates for risperidone clearance were genetic polymorphisms of CYP2D6*10, including CYP2D6*1/*10 (27.5?% decrease) and CYP2D6*10/*10 (63.8?% decrease). There was significant difference in the absorption rate constant (k ( a )) of risperidone among the CYP2D6*10 genotype groups. In addition, combined ABCB1 3435C>T and CYP2D6*10 genotypes had a significant (P?T as covariates was successfully constructed. The estimated contribution of genetic polymorphisms in CYP2D6*10 and ABCB1 3435C>T to population pharmacokinetics of risperidone and 9-hydroxyrisperidone suggests the interplay of CYP2D6 and ABCB1 on the pharmacokinetics of risperidone and 9-hydroxyrisperidone according to genetic polymorphisms.     

Pharmacogenetics of toxicity, plasma trough concentration and treatment outcome with nevirapine-containing regimen in anti-retroviral-naïve HIV-infected adults: an exploratory study of the TRIANON ANRS 081 trial

Abstract: The aim of this exploratory study was to investigate in a homogeneous population of anti‐retroviral naïve HIV‐1‐infected adults, the relationships between genetic polymorphisms involved in nevirapine metabolism [CYP2B6 516G>T, 785A>G and 1459C>T; CYP3A5 6986A>G (CYP3A5*3)], transport (ABCB1 2677G>T/A and 3435C>T), and antigen recognition (HLA‐DRB1*0101), and the hepatic and/or cutaneous toxicity occurring within the first 8 or 72 weeks of treatment, plasma trough concentrations (C_trough) at week 8 and immuno‐virological response to nevirapine at week 24. Associations between genetic polymorphisms and toxicity, C_trough and response to nevirapine were performed in a population of 72 HIV‐1 positive and nevirapine‐treated patients followed during 72 weeks, as part of the previous study called: ANRS081 ‘Trianon’ trial. Among the 18 patients who developed toxicity events during the 72 weeks of the study, 12 patients exhibited early toxicity before week 8. No significant association could be evidenced between any of the analysed single nucleotide polymorphisms (SNPs) and nevirapine early or global toxicity, pharmacokinetics and immuno‐virological responses even though a possible association between CYP2B6 516G>T and 1459C>T and the trough level of nevirapine was suggested.     

Functional evaluation of polymorphisms in the human ABCB1 gene and the impact on clinical responses of antiepileptic drugs

OBJECTIVE: The ABCB1 haplotype combinations have been demonstrated to be associated with epilepsy treatment outcomes. The aim of this study is to investigate whether ABCB1 haplotype combinations would affect P-glycoprotein (Pgp) function and impact the clinical responses of antiepileptic drugs (AEDs). METHODS AND RESULTS: Transport of substrate rhodamine 123 and calcein-AM by human Pgp carrying 12 haplotype combinations of 1236C>T, 2677G>T/A and 3435C>T were assayed in the absence and presence of known inhibitors and AEDs. The inhibitory potency of the tested drugs from the dose-response relationships was cyclosporin A>verapamil> phenytoin> carbamazepine> lamotrigine>phenobarbital>valproic acid, levetiracetam, gabapentin. The silent polymorphisms combination (1236T-3435T) and triple haplotypes (1236T-2677A/T-3435T) resulted in profoundly less effective inhibition against substrates with significantly lower intracellular substrate concentration. These results confirmed that ABCB1 polymorphisms were associated with clinical responses of AEDs. CONCLUSION: Our findings demonstrated that human ABCB1 polymorphisms may alter the interactions between Pgp and substrates, and provided functional evidence for ABCB1 haplotypes-associated epilepsy treatment responses.     

P-glycoprotein: tissue distribution, substrates, and functional consequences of genetic variations

P-glycoprotein (ABCB1, MDR1) belongs to the ABC transporter family transporting a wide range of drugs and xenobiotics from intra- to extracellular at many biological interfaces such as the intestine, liver, blood-brain barrier, and kidney. The ABCB1 gene is highly polymorphic. Starting with the observation of lower duodenal protein expression and elevated digoxin bioavailability in relation to the 3435C>T single nucleotide polymorphism, hundreds of pharmacokinetic and outcome studies have been performed, mostly genotyping 1236C>T, 2677G>T/A, and 3435C>T. Though some studies pointed out that intracellular concentrations of anticancer drugs, for example, within lymphocytes, might be affected by ABCB1 variants resulting in differential outcome, current knowledge of the functional significance genetic variants of ABC membrane transporters does not allow selection of a particular SNP to predict an individual's pharmacokinetics.     

Cytochrome P450 and ABCB1 genetics: association with quetiapine and norquetiapine plasma and cerebrospinal fluid concentrations and with clinical response in patients suffering from schizophrenia. A pilot study

Variability in response to atypical antipsychotic drugs is due to genetic and environmental factors. Cytochrome P450 (CYP) isoforms are implicated in the metabolism of drugs, while the P-glycoprotein transporter (P-gp), encoded by the ABCB1 gene, may influence both the blood and brain drug concentrations. This study aimed to identify the possible associations of CYP and ABCB1 genetic polymorphisms with quetiapine and norquetiapine plasma and cerebrospinal fluid (CSF) concentrations and with response to treatment. Twenty-two patients with schizophrenia receiving 600?mg of quetiapine daily were genotyped for four CYP isoforms and ABCB1 polymorphisms. Quetiapine and norquetiapine peak plasma and CSF concentrations were measured after 4 weeks of treatment. Stepwise multiple regression analysis revealed that ABCB1 3435C?>?T (rs1045642), 2677G?>?T (rs2032582) and 1236C?>?T (rs1128503) polymorphisms predicted plasma quetiapine concentrations, explaining 41% of the variability (p?=?0.001). Furthermore, the ABCB1 polymorphisms predicted 48% (p?=?0.024) of the variability of the Δ PANSS total score, with the non-carriers of the 3435TT showing higher changes in the score. These results suggest that ABCB1 genetic polymorphisms may be a predictive marker of quetiapine treatment in schizophrenia.     

Associations between the functional polymorphisms in the ABCB1 transporter gene and colorectal cancer risk: a case-control study in Turkish population

Abstract

Colorectal cancer is among the most common cancer types in the world and its etiology involves the interaction of genetic and environmental factors. ABCB1 is highly expressed in the apical surface of colonic epithelial cells and acts as an efflux pump by transporting toxic endogenous substances, drugs and xenobiotics out of cells. ABCB1 polymorphisms may either change its protein expression or alter its function. Several studies have reported a possible association between ABCB1 variants and colorectal cancer, but no consistent conclusion has been arrived at. Therefore, we aimed to investigate the relationship between colorectal cancer and the functional common variants of ABCB1 (1236C?>?T; 2677G?>?T/A; 3435C?>?T). The distributions of the variants were determined in 103 patients with colorectal cancer and 150 healthy volunteers using polymerase chain reaction–restriction fragment length polymorphism methods. ABCB1 1236C?>?T was statistically significantly associated with colorectal cancer risk (OR, odd ratio?=?1.91; 95% CI, confidence interval?=?1.09–3.35; p?=?0.034). In haplotype-based analysis, the proportion of individuals with the ABCB1 haplotype C₁₂₃₆-G₂₆₇₇-T₃₄₃₅ was significantly more common in patients than in controls (OR?=?11.96; 95% CI?=?2.59–55.32; p?=?0.0004). We believe that the findings may be beneficial to the development of efficacious preventive strategies and therapies for colorectal cancer.     

No influence of 3435C>T ABCB1 (MDR1) gene polymorphism on risk of adult acute myeloid leukemia and P-glycoprotein expression in blast cells

Inherited differences in xenobiotic transport and metabolism may play an important role in the development of adult acute myeloid leukemia (AML) and response to the chemotherapy. An ATP-binding cassette (ABC) family transporter P-glycoprotein (P-gp or ABCB1), encoded by ABCB1 (MDR1) gene, is involved in the protection against xenobiotics and multi-drug resistance. The aim of this study was to investigate the potential involvement of the ABCB1 gene exon 26 3435C>T single nucleotide polymorphism (SNP) in the genetic susceptibility to AML and regulation of P-gp expression and activity in AML cells. A total of 180 adult AML patients and 180 sex-matched controls were genotyped using PCR-RFLP method. Moreover, in 40 AML patients ABCB1 gene expression was studied by real-time RT-PCR and P-gp expression and activity were assessed by flow cytometry assays. The prevalence of 3435C>T ABCB1 polymorphism was similar in patient and control cohorts (P = 0.16). Furthermore, the carriers of different ABCB1 genotypes did not differ significantly according to ABCB1 gene expression (P = 0.99), P-gp expression (P = 0.42) and P-gp activity (P = 0.83) in leukemic cells. The authors conclude that isolated 3435C>T ABCB1 SNP is not a major factor of the genetic susceptibility to adult AML, and that genotyping of this polymorphism does not allow predicting P-gp expression or activity in AML cells.     

基因多态性与糖皮质激素诱导性股骨头坏死的相关性meta分析

目的 应用meta分析证实靶基因的多态性是否与糖皮质激素诱导性股骨头坏死（steroid-induced osteonecrosis of the femoral head,SONFH）发生相关。方法 检索PubMed、Embase、The Cochrane Library、Clinical Trial、CBM、万方、维普和CNKI等数据库中已发表的文章以获得适宜的研究,并以固定或者随机效应模型计算最终的OR值和95%置信区间（95%CI）。结果 检索共发现有37项研究包含41个与SONFH发生风险相关的基因多态性位点。选择含有≥3个适宜研究的多态性位点进入meta分析,纳入的多态性位点主要集中在3个基因即PAI-1、MTHFR和ABCB1。携带有PAI-1突变基因5G的患者应用糖皮质激素后易发生SONFH,但差异不具有统计学意义[OR=0.95,95%CI（0.54,1.67）,P=0.85]。SONFH发生率在MTHFR突变型和野生型之间差异存在统计学意义[OR=0.69,95%CI（0.50,0.95）,P=0.02],携带有MTHFR 677T的患者较易发生SONFH。携带ABCB1 3435C等位基因者发生SONFH的风险更高,具有显著的统计学差异[OR=1.40,95%CI（1.11,1.76）,P=0.005];而ABCB1 G2677T/A位点的基因多态性与SONFH发生之间无明显的统计学差异[OR=1.32,95%CI（0.76,2.28）,P=0.32]。结论 MTHFR C677T和ABCB1 C3435T基因的多态性与股骨头坏死的发生风险显著相关。     

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 C3435T基因多态性检测的RA患者病例64例,回顾性分析相关基因型分布情况及基因多态性与疗效的影响。结果64例RA患者中MTHFR C677T基因位点CC、CT、TT型分布频率为46.88%,40.62%,12.50%;MTHFR A1298C基因位点AA、AC、CC型分布频率为78.13%,18.75%,3.12%;ABCB1 C3435T基因位点CC、CT、TT型分布频率为51.56%,34.38%,14.06%,均符合Hardy-Weinberg遗传平衡(P>0.05)。MTHFR C677T、MTHFR A1298C、ABCB1 C3435T基因多态性与药物疗效未观察到明显相关性。64例RA患者中至少发生一个基因位点改变为51例,基因突变率为79.69%,基因突变的发生可能影响红细胞沉降率、丙氨酸氨基转移酶的数值改变。结论相同地区同种疾病患者间基因多态性存在明显的个体差异,MTHFR、ABCB1基因多态性的改变可能与小剂量MTX的治疗效果或毒副反应有关。