MDR1基因G2677T/C3435T多态性对鼻咽癌放疗疗效的影响

目的探讨多药耐药基因（MDR1）21外显子G2677T和26外显子C3435T多态性对鼻咽癌根治性放疗疗效的影响。方法采用PCR和限制性片断长度多态性（RFLP）对59例鼻咽癌患者行MDR1基因分型,并用测序法验证。结果G2677T GG基因型携带者行根治性放疗的效果优于GT和TT基因型,但差异无显著性;C3435T CC基因型携带者放射敏感性显著强于CT和TT基因型携带者（P=0．026）。结论MDR1基因多态性可作为鼻咽癌患者放射敏感度的遗传学标志。     

NSCLC患者XPG、MDR-1基因单核苷酸多态性与铂类药物化疗疗效的关系

目的探讨晚期非小细胞肺癌（NSCLC）患者XPG、MDR-1基因单核苷酸多态性与铂类药物短期化疗疗效的关系。方法对61例晚期NSCLC患者，采用顺铂（DDP）为主的化疗方案治疗，2～3个周期后进行临床疗效评价。以PCR—RLFP方法进行XPGC3507G、MDR-1C3435T、MDR-1G2677A／T的基因型分析，比较不同基因型患者的化疗效果。结果MDR1C3435T型为C／C者的化疗有效率为59．3％，显著高于至少含有一个T等位基因者的26．5％（OR=0．442，95％CI=0．133～1．467，P〈0．05）；MDR-1G2677A／T位点至少一个T等位基因者的化疗有效率13．0%，要显著低于其他基因型者的57．9％（OR=0．384，95％CI=0．187～0．789，P〈0．01）；XPGC3057位点各基因型化疗有效率差异无统计学意义。结论MDR-1C3435T、MDR-1G2677A／T位点多态性可降低铂类药物治疗治疗NSCLC的疗效。XPGC3507G位点多态性对铂类药物治疗NSCLS疗效无影响。     

MDR1、CYP3A 基因多态性对维吾尔族、汉族心力衰竭患者地高辛血药浓度的影响

目的：观察多药耐药基因1（MDR1） C3435T、细胞色素P450（CYP）3A4*18B对维吾尔族、汉族充血性心力衰竭（简称心衰）患者地高辛血药浓度的影响。方法选择维吾尔族、汉族心衰患者各40例,均口服地高辛0．125 mg/（次· d）至少1周。抽取清晨空腹静脉血后,采用PCR-RFLP法检测患者MDR1 C3435T、CYP3A4*18B基因型,日立741-0050全自动生化分析仪检测地高辛血药浓度。结果汉族MDR1 C3435T基因CT、TT型患者地高辛血药浓度均高于 CC 型和维吾尔族同基因型, P 均＜0．05;维吾尔族 MDR1 C3435T 各基因型及两民族CYP3A4*18B各基因型患者地高辛血药浓度比较,P均＞0．05。结论 MDR1 C3435T基因多态性可能会提高汉族心衰患者的地高辛血药浓度,但对维吾尔族患者则无影响;而CYP3A4*18B基因多态性对两民族心衰患者的地高辛血药浓度均没有明显影响。     

多药耐药基因MDR1 C3435T基因多态性对根除幽门螺杆菌疗效的影响

目的研究多药耐药基因MDR1 C3435T基因多态性对质子泵抑制剂联合阿莫西林与克拉霉素三联1周疗法根除幽门螺杆菌（砀,）治疗的影响。方法选取101例却阳性的慢性胃炎或消化性溃疡患者,分成2组,分别进入埃索美拉唑联合阿莫西林与克拉霉素方案（EAC）或奥美拉唑联合阿莫西林与克拉霉素方案（OAC）进行1周根除治疗。采用聚合酶链反应-限制性内切片段长度多态性（polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP）的方法检测MDR1 C3435T基因型,比较不同基因型患者之间埤,根除率的差异。结果MDR1 CC3435、C3435T和3435TT的却根除率分别为72．4％、88．2％和81．0％。MDR1 C3435T各基因型组间却根除率比较均元显著性差异。结论MDR1 C3435T基因多态性与却根除疗效无显著相关性。     

MDR1 C3435T基因多态性对胃溃疡患者抗Hp治疗效果的影响

目的探讨多耐药基因(MDR)1 C3435T多态性对幽门螺杆菌(HP)感染胃溃疡患者治疗效果的影响。方法选取80例HP阳性胃溃疡患者为观察组,另选取80例非HP阳性胃溃疡患者及正常体检者为对照1组及对照2组,采用聚合酶链式反应(PCR)测定三组MDR1 C3435T基因多态性。观察组患者给予三联疗法(兰索拉唑+阿莫西林+克拉霉素)治疗,分析不同基因型HP阳性胃溃疡患者治疗后HP阳性率及耐药率。结果与对照1组及对照2组相比,观察组患者TT型MDR1 C3435T基因比例显著高于对照组,T等位基因频率高于对照1组及对照2组(P<0.05)。与对照2组相比,对照1组患者CT型、TT型MDR1 C3435T基因比例及T等位基因频率较高(P<0.05)。观察组患者中TT基因型患者经三联疗法治疗后HP阳性率及耐药率较高(P<0.05)。结论 MDR1 C3435T基因型可影响HP阳性胃溃疡患者三联疗法治疗效果,其中TT型基因的HP阳性胃溃疡患者HP根治率较低,耐药性较高。     

中国大陆汉族肾移植受者CYP3A5和MDR1基因多态性研究

目的建立细胞色素P450-3A5（CYP3A5）和多药耐药基因1（MDR1）3435、2677、1236基因多态性检测方法,并研究中国大陆汉族肾移植受者其基因多态性分布情况。方法自行设计引物,采用PCR法一次性扩增目的DNA,变性高效液相色谱技术检测分型。对在解放军第474医院肾移植中心及南方医院器官移植中心行肾移植手术及复诊的274例来自中国大陆12个省份的汉族肾移植受者CYP3A5和MDR1 3435、2677、1236基因多态性及分布情况进行分析,并观察是否存在省份差异,统计学方法采用多个独立样本比较的χ2检验。结果中国大陆汉族肾移植受者存在CYP3A5＊3、MDR1 3435C〉T、MDR1 2677G〉T/A、MDR1 1236C〉T基因变异,其变异频率分别为74.1%、49.5%、39.9%/13.7%、72.1%,不同省份间无统计学差异。结论中国大陆不同省份间汉族肾移植受者CYP3A5＊3、MDR1（3435、2677、1236）基因变异无明显差异,但对于遗传基因相对较纯的小群体汉族和少数民族而言,仍有深入研究的意义。     

多药耐药性基因1(MDR1)基因多态性对丙戊酸钠治疗老年癫痫血药浓度的影响

目的 探讨多药耐药性基因1(multidrug resistance 1 gene, MDR1)基因多态性对丙戊酸钠治疗老年癫痫血药浓度的影响。方法 选择2021年10月1日—2022年10月1日于淮北矿工总医院诊治的老年癫痫患者86例为研究对象，采用多聚酶连锁反应-限制性片段长度多态性(Polymerase chain reaction-restriction fragment length polymorphism, PCR-RFLP)和测序技术确定MDR1 C3435T位点基因型分布情况，采用柱前衍生化法(HPLC法)测定丙戊酸血清药物浓度，分析MDR1 C3435T基因多态性与丙戊酸钠治疗老年癫痫血药浓度的相关性。结果 不同MDR1 C3435T基因型患者丙戊酸钠血药浓度差异有统计学意义(P<0.05)。与CC基因型组比较，TT基因型组和CT基因型组的丙戊酸钠血药浓度均显著升高(P<0.05)。老年癫痫患者使用丙戊酸钠后，突变组胃肠道反应、嗜睡、肝功能异常、肾功能异常等总不良反应发生率显著高于CC基因型组(P<0.05)。结论 MDR1 C3435T的TT基因...     

MDR1 G2677T基因多态性在预测紫杉醇为主的化疗方案治疗晚期消化系难治性恶性肿瘤疗效中的价值

目的:探讨MDR1 G2677T基因多态性与紫杉醇为主的化疗方案治疗晚期消化系难治性恶性肿瘤疗效的关系.方法:97例晚期消化系难治性恶性肿瘤患者给予以紫杉醇为主的化疗方案(130 mg/m~2,静脉滴注,d1、8,21 d为1周期),评价疗效,于治疗前抽取患者外周血提取DNA,采用PCR扩增目的基因片段,直接测序法测定MDR1G2677T基因多态性,分析MDR1 G2677T基因多态性与疗效关系.结果:最终有94例患者完成了本研究,其中完全缓解(complete response,CR):2例,部分缓解(partial response,PR):24例,疾病稳定(stable disease,SD):54例,疾病进展(progressive disease,PD):14例,总缓解率为27.66%.MDR1 G2677T基因野生型G/G有32例,突变型中有62例(A/A有6例,T/T有14例,G/A有10例,G/T有12例,A/T有20例),两类基因型与肿瘤发生部位无明显相关性.MDR1G2677T基因多态性与疗效相关(P0.05),其中仅MDR1 G2677T野生型G/G对疗效的影响有统计学意义(P0.01).结论:MDR1 G2677T基因多态性可作为遗传学标志预测紫杉醇对晚期消化系难治性恶性肿瘤患者的化疗敏感性,野生型G/G基因携带者化疗疗效优于其他基因型携带者.     

α-内收蛋白基因及内皮型一氧化氮合酶基因多态性与大动脉弹性相关性研究

目的 探讨α-内收蛋白基因变异（Gly460Trp）及内皮型一氧化氮合酶基因（G894T、T786C）变异与大动脉弹性相关性研究。方法 （1）采用Complior SP脉搏波速度测定仪测量股-颈动脉PWV（C—FPwV），共319例，其中C—FPWV异常组204例，对照组115例；（2）采用聚合酶链反应和限制性酶切的片段长度多态分析方法检测α-内收蛋白基因变异（Gly460Trp）及一氧化氮合酶（eNOS）基因变异（G894T、T786C）。结果 （1）C—FPWV升高组收缩压（SBP）、舒张压（DBP）均显著高于对照组（P〈0．05）；（2）C—FPWV异常组WW、TG＋TT基因型、W、T等位基因频率显著高于对照组（P〈0．05）。C—FPWV异常组T786C（CT、CC）基因型及C等位基因频率与对照组比较差异无显著性（P〉0．05）；（3）WW和TG＋TT基因型与WG＋GG、TT基因型比较C—FPWV、收缩压、舒张压差异有显著性（P〈0．05）；（4）Logistic回归结果显示：α-内收蛋白460WW基因型（P=0．001，OR=3．234，95％CI1．655—6．320）及内皮型一氧化氮合酶（eNOS）基因G894T多态性TT、TG基因型是动脉弹性减退的危险因素（P=0．025，OR=0．477，95％C10．249～0．911）结论 α-内收蛋白基因变异（Gly460Trp）及一氧化氮合酶基因变异（G894T）与大动脉弹性有密切相关性，WW、TT、TG型是大动脉弹性减退的敏感基因型。     

普乐可复血药浓度与肝药酶P450 3AP1和多药耐药基因多态性的关系

目的 :探讨普乐可复血药浓度的个体间差异与其在体内吸收、代谢相关基因肝药酶P4 5 0 3AP1(CYP3AP1)和多药耐药基因 1(MDR1)多态性的关系。　 方法 :观察 4 1例口服普乐可复治疗的狼疮或膜性肾病患者的体重、普乐可复剂量、普乐可复全血谷浓度 ,并利用PCR 限制性片断长度多态性的方法检测患者CYP 3AP1基因— 4 4位A/G和MDR1基因 3435位C/T多态性 ,分析浓度 /剂量比与基因型的关系。　 结果 :CYP 3AP1基因为AA型患者的血药浓度明显高于AG或GG型 (15 1 3± 93 4 ,n =2 1vs6 9 2± 39 4 ,n =2 0 ,P <0 0 0 1) ,MDR1基因为CC型患者的血药浓度明显低于CT或TT型 (73 7± 38 2 ,n =12vs 12 6 8± 91 3,n =2 9,P <0 0 5 )。　 结论 :CYP 3AP1和MDR1基因多态性与普乐可复的血药浓度显著相关。根据上述基因不同基因型药物代谢的特点 ,有针对性地进行剂量调整 ,或在用药前通过检测基因型更合理地选择患者 ,有助于提高普乐可复的疗效 ,减少其副作用     

The association between multidrug resistance-1 gene polymorphisms and outcomes of allogeneic HLA-identical stem cell transplantation

The impact of single nucleotide polymorphisms of two loci (C3435T and G2677T/A) of the multidrug resistance-1 gene (MDR1) was investigated in 82 patients undergoing allogeneic stem cell transplantation (SCT). The GG genotype on G2677T/A loci was associated with higher non-relapse mortality than was the non-GG genotype (67% vs. 32%, p=0.0073), but not the C3435T (p=0.2026) or MDR1 haplotype (p=0.2238). Accordingly, overall survival was significantly correlated with the G2677T/A genotype (p=0.0048). Multivariate analysis also showed that the GG genotype at G2677T/A had an unfavorable prognosis in terms of overall survival (p=0.003) and non-relapse mortality (p=0.031). In conclusion, the G2677T/A genotype seems to be associated with transplantation outcomes, especially non-relapse mortality.     

Multidrug resistance gene-1 polymorphisms and resistance to cyclosporine A in patients with steroid resistant ulcerative colitis

BACKGROUND: Cyclosporine A (CsA) is inconstantly effective in inducing remission in acute attacks of ulcerative colitis (UC) not responding to steroids. This study aimed to establish whether multidrug resistance gene (MDR)1 polymorphisms would be associated with CsA failure. PATIENTS AND METHODS: The distribution of the different genotypes of single nucleotide polymorphisms (SNP) G2677T/A and C3435T of MDR1 exons 21 and 26, respectively, was studied in 154 patients (mean age, 44 yr) who had received CsA to treat severe attacks of steroid resistant UC in 11 centers in France and Belgium. Patients were classified as CsA failure (n = 50) when they needed colectomy within 30 days after CsA initiation. The SNPs were detected by use of a 5' nuclease allelic discrimination assay. RESULTS: There was a significant association between the G2677T/A polymorphism distribution (exon 21) and the risk for CsA failure (P = 0.0001). The TT genotype of exon 21 was significantly associated with the risk compared with the two other genotypes (odds ratio, 3.77; 95% confidence interval, 1.42-9.97, P = 0.007). There was no significant association between the genotype C3435T distribution (exon 26) and the risk of CsA failure (P = 0.23). CONCLUSION: The TT genotype of exon 21 MDR1 polymorphisms is associated with a higher risk of CsA failure in patients with steroid resistant UC. Further studies should be performed to establish whether other treatments could be more efficient to avoid surgery in this subset of patients.     

MDR1 polymorphisms and response to azathioprine therapy in patients with Crohn's disease

BACKGROUND: To investigate the contribution of multidrug resistance 1 (MDR1) gene pharmacogenetics (G2677T/A and C3435T) to the efficacy of azathioprine in inducing remission in patients with Crohn's disease (CD). METHODS: A cohort of 327 unrelated Spanish patients with CD recruited from a single center was studied. All patients were rigorously followed up for at least 2 years (mean time, 11.5 years). A case-control analysis of MDR1 G2677T/A and C3435T SNPs and 2 loci haplotypes in 112 steroid-dependent CD patients treated with azathioprine was performed. Patients were classified on the basis of response to azathioprine. RESULTS: A total 76 patients treated with azathioprine for longer than 3 months were included. Remission was achieved in 42 CD patients (55.3%). A higher frequency of the 2677TT genotype was found in nonresponders than in responders (17.65% versus 7.14%; OR = 2.8; 95% CI; 0.6-12.1; P = 0.11). Nonresponders to azathioprine were found to have a higher frequency of the 3435TT genotype than did CD patients who had achieved clinical remission (17.64% versus 4.76%; OR = 4.3; 95% CI, 0.8-22.8; P = 0.06). The 2677T/3435T haplotype was also more abundant in nonresponders (29.4% versus 20.2%), whereas the 2677G/3435C haplotype was more frequent in responders (58.3% versus 47.1%). Lack of response to azathioprine therapy in CD patients was 1.8-fold greater in carriers of the 2677T/3435T haplotype than in carriers of the 2677G/3435C haplotype (OR = 1.8; 95% CI, 0.82-3.9; P = 0.14). CONCLUSIONS: The results of our study indicate higher frequencies of the 2677TT and 3435TT genotypes and the 2677T/3435T haplotype in CD patients who did not respond to azathioprine. Additional replications in independent populations would confirm the real impact of these polymorphisms in response to azathioprine therapy.     

Allelic variations of the multidrug resistance gene determine susceptibility and disease behavior in ulcerative colitis

BACKGROUND AND AIMS: The MDR1 gene encodes P-glycoprotein 170, an efflux transporter that is highly expressed in intestinal epithelial cells. The MDR1 exonic single nucleotide polymorphisms (SNPs) C3435T and G2677T have been shown to correlate with activity/expression of P-glycoprotein 170. METHODS: This was a case-control analysis of MDR1 C3435T and G2677T SNPs in a large well-characterized Scottish white cohort (335 with ulcerative colitis [UC], 268 with Crohn's disease [CD], and 370 healthy controls). We conducted 2-locus haplotype and detailed univariate and multivariate genotypic-phenotypic analyses. RESULTS: The MDR1 3435 TT genotype (34.6% vs 26.5%; P = .04; odds ratio [OR], 1.60; 95% confidence interval [95% CI], 1.04-2.44) and T-allelic frequencies (58.2% vs 52.8%; P = .02; OR, 1.28; 95% CI, 1.03-1.58) were significantly higher in patients with UC compared with controls. No association was seen with CD. The association was strongest with extensive UC (TT genotype: 42.4% vs 26.5%; P = .003; OR, 2.64; 95% CI, 1.34-4.99; and T allele: 63.9% vs 52.8%; P = .009; OR, 1.70; 95% CI, 1.24-2.29), and this was also confirmed on multivariate analysis ( P = .007). The G2677T SNP was not associated with UC or CD. These 2 SNPs lie in linkage disequilibrium in our population (D', .8-.9; r 2 , .7-.8). Two-locus haplotypes showed both positive (3435T/G2677 haplotype: P = .03; OR, 1.44) and negative (C3435/2677T haplotype: P = .002; OR, .35) associations with UC. Homozygotes for the haplotype 3435T/G2677 were significantly increased in UC ( P = .017; OR, 8.88; 95% CI, 1.10-71.45). CONCLUSIONS: Allelic variations of the MDR1 gene determine disease extent as well as susceptibility to UC in the Scottish population. The present data strongly implicate the C3435T SNP, although the 2-locus haplotype data underline the need for further detailed haplotypic studies.     

Multidrug resistance 1 gene polymorphism and susceptibility to inflammatory bowel disease

BACKGROUND: Several studies have evaluated the role of the multidrug resistance 1 gene (MDR1) polymorphism, which encodes the membrane-bound efflux transporter P-glycoprotein 170, in determining susceptibility to and disease behavior in inflammatory bowel disease (IBD), but with conflicting results. METHODS: A total of 211 patients with Crohn's disease (CD), 97 patients with ulcerative colitis (UC), and 212 control subjects were investigated for the presence of MDR1 G2677T/A and C3435T polymorphisms. Genotype frequencies of CD and UC patients were compared to those observed in a control population. Genotype-phenotype correlations with major clinical features were also established and estimated risks (odds ratio [OR] with 95% confidence interval [CI]) for the mutations were calculated by a logistic regression analysis and multiple correspondent analysis. RESULTS: No significant difference was observed for genotype frequencies for both MDR1 G2677T/A and C3435T polymorphisms on overall disease susceptibility for either CD or UC patients compared with control subjects. A significant association was found between the MDR1 C3435T polymorphism and patients with ileo-colonic CD (OR = 3.34; 95% CI: 1.34-8.27). Interestingly, a negative association was found between MDR1 C3435T polymorphism in patients with a positive family history for IBD (OR = 0.44; 95% CI: 0.20-0.95) and articular manifestations (OR = 0.29; 95% CI: 0.13-0.68). Both susceptible and protective effects were identified. No significant association between G2677T/A polymorphism and any specific subphenotypes was found, nor was there any association with subphenotypic categories of UC and both single nucleotide polymorphisms. CONCLUSIONS: The results of our study suggest that MDR1 gene polymorphism could have a role in determining susceptibility to IBD. The variability of this possible effect in the several studies reported so far may be the indirect expression of the complex role played by the MDR1 gene and its product, P-glycoprotein 170, in the regulation of host-bacteria interactions and in the pathogenesis of IBD.     

Identification of polymorphisms on the MDR1 gene among Turkish population and their effects on multidrug resistance in acute leukemia patients

Multidrug-resistance (MDR) phenotype is a serious limitation to the effective chemotherapeutic treatment of many cancer types, including leukemia. One of the most important proteins, the over-expression of which is responsible for the multidrug-resistance phenotype in many cancer types, is P-glycoprotein. This protein is the product of the MDR1 gene. In previous studies, single-nucleotide polymorphisms (SNPs) C3435T, G2677T, and T-129C in the MDR1 gene were shown to be correlated with lower P-glycoprotein expression in normal tissues. It was suggested that this might have an advantage in cancer chemotherapy by resulting in a low drug-resistance phenotype. The frequencies of these SNPs were studied in 45 acute leukemia patients (25 of which were primary refractory and 20 of which were drug-sensitive) and 17 healthy individuals, forming a Turkish population of 62 individuals. In the first part of the study, these polymorphisms were compared with other populations. Marked differences were apparent between African and Turkish populations for the C3435T polymorphism. On the other hand, similarities were found between other Caucasian/Asian and Turkish populations (P < 0.001). However, for the G2677T polymorphism, the Turkish population is different than Japanese and German populations (P < 0.001). For the T-129C polymorphism, all individuals in the studied population were homozygous for the T/T genotype. In the second part of this study, drug-resistant and drug-sensitive acute leukemia patients were compared for these SNPs. These polymorphisms did not seem to have a significant effect on P-glycoprotein-mediated drug resistance in the patients studied.     

Influence of functional MDR1 gene polymorphisms on P-glycoprotein activity in CD34+ hematopoietic stem cells

BACKGROUND AND OBJECTIVES: Expression of the multidrug resistance P-glycoprotein, a transmembrane drug transporter, is influenced by recently described polymorphisms of the human MDR1 gene. Hematopoietic cells, such as lymphocytes, and hematopoietic stem cells, express P-glycoprotein, but the effect of MDR1 gene polymorphisms on P-glycoprotein activity in stem cells is unknown. We investigated whether T-129C, G26677T and C3435T polymorphisms influence P-glycoprotein function in stem cells. DESIGN AND METHODS: P-glycoprotein function was evaluated in immunomagnetically purified bone marrow CD34+ cells from 33 healthy bone marrow donors by the flow cytometric rhodamine 123-efflux assay. For T-129C and C3435T, bone marrow donors were genotyped by polymerase chain reaction amplification followed by MspA1I and DpnII digestion analyses, respectively. For the analysis of C2677T, exon 21 was sequenced. RESULTS: P-glycoprotein function was not different among the C3435T genotypes (CC, 38.2 +/- 3.5%; n=17; CT, 42.2 +/- 3.3%; n=11; and TT, 45.0 +/- 5.3%; n=5) nor was it among the C2677T genotypes (CC, 39.4 +/- 2.4%; n=27; CT, 43.7 +/- 6.4%; n=5; and TT, 54.3%; n=1). Among the 33 subjects, three were heterozygotes for the 129C allele (CT) and no mutant homozygote was identified. P-glycoprotein was similar in heterozygotes (TC, 50.6 +/- 2.9%) and wild-type subjects (TT, 39.5 +/- 2.4%). INTERPRETATION AND CONCLUSIONS: These findings suggest that the known functional MDR1 gene polymorphisms are not major determinants of P-glycoprotein function in hematopoietic stem cells. Other genetic variants might influence P-glycoprotein activity in this cell type.     

MDR1 gene: susceptibility in Spanish Crohn's disease and ulcerative colitis patients

BACKGROUND: The multidrug resistance MDR1 gene codes for a membrane transporter associated with inflammatory bowel disease. The polymorphism Ala893Ser/Thr (G2677T/A) previously showed significant association with Crohn's disease (CD) and the Ile1145Ile (C3435T) with ulcerative colitis (UC). We studied the association of both polymorphisms in an independent population to reveal the impact of the MDR1 gene on predisposition to inflammatory bowel disease. METHODS: Case-control study with 321 CD and 330 UC white Spanish patients recruited from the same center, and 352 healthy ethnically matched controls. RESULTS: A significant association of MDR1 C3435T with CD was observed (CC vs (CT + TT): P = 0.007; OR [95% CI] = 1.58 [1.12-2.23]). A CD susceptibility haplotype 2677T/C3435 was identified. No difference between UC patients as a whole and controls could be detected. CONCLUSIONS: New evidence supports the role of the MDR1 gene on CD susceptibility. Therefore, considering our results and those from others, the MDR1 gene behaves as a common risk factor for both CD and UC. We discovered that the C3435 allele conferring susceptibility to CD is different from the described 3435T UC risk allele.     

Multidrug resistance gene (MDR1) polymorphisms are associated with major molecular responses to standard-dose imatinib in chronic myeloid leukemia

Despite the excellent efficacy of imatinib in chronic myeloid leukemia (CML), the response in patients is heterogeneous, which may in part be caused by pharmacogenetic variability. Imatinib has been reported to be a substrate of the P-glycoprotein pump. In the current study, we focused on the ABCB1 (MDR1) genotype. We analyzed the 3 most relevant single nucleotide polymorphisms of MDR1 in 90 CML patients treated with imatinib. Among the patients homozygous for allele 1236T, 85% achieved a major molecular response versus 47.7% for the other genotypes (P = .003). For the 2677G>T/A polymorphism, the presence of G allele was associated with worse response (77.8%, TT/TA; vs 47.1%, GG/GA/GT; P = .018). Patients with 1236TT genotype had higher imatinib concentrations. One of the haplotypes (1236C-2677G-3435C) was statistically linked to less frequent major molecular response (70% vs 44.6%; P = .021). Hence, we demonstrated the usefulness of these single nucleotide polymorphisms in the identification of CML who may or may not respond optimally to imatinib.