共查询到20条相似文献,搜索用时 46 毫秒
1.
目的 探讨高原人群基于中国人群华法林用药剂量计算公式(PRC模型)和国际华法林遗传药理学协会推荐的亚裔人群华法林剂量计算公式(IWPC模型)两种模型预测剂量的准确性及其临床应用价值。方法 回顾性分析曲靖市第一人民医院2016年10月—2020年1月375例行华法林代谢基因多态性检测患者的临床资料。通过qRT-PCR检测CYP2C9和VKORC1基因多态性,记录患者基本信息和临床用药情况,采用两种模型计算预测剂量并分析其与维持剂量[国际标准化比值(INR)稳定维持在2.0~3.0范围内时所服用的华法林剂量]的相关性,评估两模型预测的准确性。结果 在实际治疗过程中患者是否选择服用华法林进行抗凝,通常与患者的性别、身高、吸烟史、是否合并房颤、是否注射低分子肝素钙无关,而与患者年龄、体重、体表面积(BSA)、初INR、是否置换主动脉瓣膜、是否服用阿司匹林、利伐沙班或氯吡格雷相关。375例患者CYP2C9和VKORC1基因频率符合Hardy-Weinberg遗传平衡定律,其中CYP2C9基因*1/*1(AA)、*1/*3(AC)及*3/*3(CC)基因型频率分别为93.07%(349/375)、6.93%(26/375)和0.00%(0/375),VKORC1-1639基因AA、AG和GG基因型频率分别为82.66%(310/375)、16.27%(61/375)和1.07%(4/375)。无论是使用PRC还是IWPC模型,除CYP2C9*1/*1 & VKORC1AA(n =289)组与CYP2C9*1/*3 & VKORC1AG(n =5)组预测剂量的差异无统计学意义(P >0.05)外,其他所有基因型组预测剂量两两比较均有差异(P <0.05)。在收集到维持剂量的174例患者中,CYP2C9*1/*1 & VKORC1 AG和CYP2C9*1/*1 & VKORC1 GG组维持剂量分别为[(3.41±1.01)mg,n =30]和[(4.75±0.35)mg,n =2],均高于CYP2C9*1/*1 & VKORC1 AA组[(2.59±0.73)mg,n =136](P <0.05);CYP2C9*1/*3 & VKORC1 AA组维持剂量为[(2.00±0.53)mg,n =5],低于其他基因型组合(P <0.05)。PRC和IWPC模型预测准确性分别为72.99%(127/174)和62.64%(109/174);Pearson相关系数(r1 =0.546,r2 =0.567);决定系数(R12=0.298,R22=0.322)。两个模型预测剂量间无差异(r =0.839,P >0.05)。结论 携带CYP2C9*3等位基因的患者对华法林更敏感,所需华法林剂量较低,而携带VKORC1-1639 G等位基因的患者需要更高剂量的华法林才可以获得有效的抗凝疗效。基因组学预测剂量可为临床使用华法林剂量提供依据,提高抗凝治疗的安全性和有效性。 相似文献
2.
目的:研究瓣膜置换术后CYP2C9*2、CYP2C9*3、CYP4F2、GGCX、VKORC1-1173、VKORC1-1639基因多态性,及人口学、临床因素对瓣膜置换术后华法林稳定剂量的影响,建立华法林稳定剂量的预测模型。方法:收集226例瓣膜置换患者,提取DNA,设计引物,应用聚合酶链式反应(PCR)技术扩增上述位点基因,应用酶切技术,以特定内切酶切出相关基因,以电泳显示最终结果,得出目标DNA基因序列,回顾追踪患者服药剂量、临床资料、人口学特征,并长期监测其INR,结合有无出血、血栓形成,得出瓣膜置换术后华法林稳定剂量预测模型。结果:得出华法林稳定剂量预测模型:Y=2.131-1.816VKORC1-1173+0.369GGCX+1.529BSA-0.013Age(V1173当基因型为AA型时,取1,非AA型取0,当GGCX为GT型时取1,非GT型取0,BSA单位为㎡,Age单位为岁)。华法林稳定剂量与体表面积、年龄、VKORC1-1173、GGCX基因型相关,与CYP2C9*2、CYP2C9*3、CYP4F2、VKORC1-1639无明显线性关系。结论: VKORC1-1173的AA基因型与年龄与华法林稳定剂量呈负相关,而GGCX的GT基因型与体表面积与华法林稳定剂量呈正相关。 相似文献
3.
N. S. Bazan N. A. Sabry A. Rizk S. Mokhtar O. A. Badary 《Irish journal of medical science》2014,183(2):161-172
Background
Warfarin is the mainstay of anticoagulation therapy worldwide. CYP2C9 and VKORC1 are two major genetic factors associated with inter-individual and inter-ethnic variability in the warfarin dose.Aim
This study aims to assess the impact of VKORC1–1639G>A polymorphism and the most common CYP2C9 variant alleles (*2 and *3) on warfarin response in Egyptian patients.Methods
Genetic analysis of VKORC1–1639G>A and CYP2C9*2, CYP2C9*3 was performed using real-time PCR system. Patients maintained on a constant dose targeting an international normalized ratio range of 2–3.5 for at least three consecutive times were considered as good candidates. A stepwise linear regression analysis was used to determine the independent effects of genetic and non-genetic factors on daily warfarin dose requirements.Results
Patients carrying VKORC1 and CYP2C9 variant genotypes needed a 44.8 % lower mean daily warfarin dose as compared to wild types. Patients with G allele for VKORC1–1639G>A had a significantly higher number of thromboembolic complications per month during therapy. On the first 30 days of therapy, presence of a variant allele either in VKORC1 or in CYP2C9 was associated with increased time required to achieve stable dosing. Multiple regression analysis showed that, VKORC1–1639G>A, age, CYP2C9*3, and smoking status explained 43.4 % of the overall variability in the warfarin dose.Conclusion
VKORC1–1639G>A and CYP2C9 polymorphisms contribute to the difference in warfarin dose requirements and quality of anticoagulation amongst Egyptian patients. Study results support using personalized warfarin treatment in Egyptian patients. 相似文献4.
目的 探讨重庆地区人工机械瓣膜置换术后患者VKORCI-1639A/G基因多态性与华法林剂量和抗凝效果的关系.方法 采用PCR-RFLP技术对100例重庆地区汉族人工机械瓣膜置换术后抗凝治疗患者VKORC1-1639A/G多态性位点进行检测,计算其基因型和等位基因频率,同时记录患者服药期间的用药剂量.结果 100例重庆地区汉族人工机械瓣膜置换术后抗凝治疗患者中共筛选到2种等位基因:A和G.等位基因频率分别为92%和8%.,同时VKORC1-1639A/G基因多态性共检测到3种基因型,以AA基因型常见,基因型频率86%,其次为AG和GG型,分别为12%和2%.在达到抗凝指标(1.5~2.0)后,含有等基因G的患者需要的华法林维持剂量[(5.27±0.55)mg]明显高于基因型为AA患者的华法林维持剂量[(2.41±0.75)mg].100例重庆地区汉族人工机械瓣膜置换术后抗凝治疗患者VKORC1-1639A/G基冈多态性与相应的患者的口服剂量有相关.结论 VKORC1基因多态性与术后扰凝治疗患者华法林维持剂量有关系. 相似文献
5.
目的 探讨维生素K环氧化物还原酶复合体亚单位1基因(VKORC1)多态性对机械心脏瓣膜置换术后妊娠期华法林抗凝效果的影响。方法 收集56例机械心脏瓣膜置换术后妊娠者,妊娠期全程口服华法林,应用聚合酶链反应、限制性片段长度多态性方法检测VKORC1基因多态性,同时记录服用华法林初始抗凝效果、维持剂量,以及妊娠结局情况。结果 VKORC1-1639AA型频率最高(78.57%),VKORC1-1639AG型频率为21.43%,未发现VKORC1-1639GG型;VKORC1-1639AA型华法林初始达标剂量、时间及维持剂量均少于VKORC1-1639AG型(P〈0.05);VKORC1-1639AA型妊娠结局优于VKORC1-1639AG型。结论 VKORC1-1639AA型对华法林敏感度更高;建议VKORC1-1639AA型妊娠期可考虑口服华法林,VKORC1-1639AG型建议联合用药。 相似文献
6.
XIE Shuang LIU Hong TIAN Lei JIANG Juan-juan CHEN Guo-liang LIU Li-wei XU Li LI Yi-shi 《中华医学杂志(英文版)》2009,122(18):2117-2122
Background The genetic variations in VKORC1 modulate the stable responses to warfarin administration. But the role of VKORC1 polymorphisms during the initial anticoagulation and elimination period in the Hart Chinese population is not clear. Methods Twenty-four healthy Chinese volunteers were grouped according to their VKORC1 genotype. Twelve subjects were in the 3 mg group and 12 in the 6 mg group. VKORC1 genotypes were determined by a polymerase chain reaction (PCR) based restriction fragment length polymorphism (RFLP) assay and sequencing. The international normalized ratio (INR) was measured with an ACL9000 coagulation analyser. Plasma free warfarin concentration was measured with LC/MS/MS. Results In the initial anticoagulation period, the -1639AG and 1173TC carriers compared with the -1639AA and 1173TT carriers had a low INR value. The differences between genotypes with regard to INR values were more obvious in the 3 mg subjects (P 〈0.05), and were not significantly different among the 6 mg subjects (P〉0.05). On the contrary, no significant difference of plasma free warfarin concentration between genotypes was observed in each dosage group. It took 96 hours for the INR value and 144 hours for the free warfarin plasma concentration to come back to baselines after the last dose. No significant difference among genotypes and dosing groups was detected in the elimination phase (P〉0.05). Conclusion VKORC1 polymorphisms are associated with differences in the initial response to warfarin when given at fixed doses, without affecting, as expected, its plasma concentration. 相似文献
7.
目的 分析中国人CYP2C9基因多态性对华法林维持剂量的影响.方法 检索2000-2011年相关中英文数据库,用stata10.0软件进行Meta分析.结果 共纳入16项研究(共2 361人).中国人CY P2C9各等位基因型频率为野生型CYP2C9*193.99%,突异型CYP2C9*2 0.06%,CYP2C9*3 5.95%.与野生型*1/*1型相比,*1/*3和*3/*3型华法林维持剂量分别减少26.8%(95%CI 18.8%,34.8%)和26.3%(95%CI 12.6%,39.9%),亚组分析、剪补法校正及敏感性分析表明该结果稳定、可信.结论 中国人CYP2C9基因多态性频率与其他种族不同,对华法林维持剂量具有重要影响. 相似文献
8.
【目的】研究肝移植供受体CYP3A5和MDR1基因多态性对患者术后他克莫司浓度/剂量比的影响。【方法】选取我中心32例肝移植供受体,测定患者术后1、2、4、12周体质量、他克莫司用量及药谷浓度等指标,采用聚合酶链式反应-限制性内切片段长度多态性(PCR-RFLP)方法测定供受体基因分型,比较不同基因型对患者他克莫司浓度/剂量比值的影响。【结果】供体CYP3A5*1/*1和*1/*3型患者术后2、4、12周他克莫司浓度/剂量比明显低于*3/*3型患者(p<0.05);受体CYP3A5*1、*3基因型,供受体MDR1 2677GG、GA基因型各组间他克莫司浓度/剂量比差异无统计学意义(P>0.05)。联合分析供受体CYP3A5基因型,术后2、4、12周,不论受体基因型如何,供体为CYP3A5*3/*3基因型患者他克莫司浓度/剂量比均高于供体为CYP3A5*1/*1和CYP3A5*1/*3基因型患者(P<0.05);供体基因型相同时,受体组间差异无统计学意义(P>0.05)。【结论】肝移植供体CYP3A5*3基因多态性与他克莫司浓度/剂量比明显相关,供体携带*1等位基因的患者需更高剂量他克莫司才能达到目标血药浓度。 相似文献
9.
Association between CYP2C9 genetic variants and anticoagulation-related outcomes during warfarin therapy 总被引:34,自引:0,他引:34
Higashi MK Veenstra DL Kondo LM Wittkowsky AK Srinouanprachanh SL Farin FM Rettie AE 《JAMA》2002,287(13):1690-1698
CONTEXT: Warfarin is a commonly used anticoagulant that requires careful clinical management to balance the risks of overanticoagulation and bleeding with those of underanticoagulation and clotting. The principal enzyme involved in warfarin metabolism is CYP2C9, and 2 relatively common variant forms with reduced activity have been identified, CYP2C9*2 and CYP2C9*3. Patients with these genetic variants have been shown to require lower maintenance doses of warfarin, but a direct association between CYP2C9 genotype and anticoagulation status or bleeding risk has not been established. OBJECTIVE: To determine if CYP2C9*2 and CYP2C9*3 variants are associated with overanticoagulation and bleeding events during warfarin therapy. DESIGN AND SETTING: Retrospective cohort study conducted at 2 anticoagulation clinics based in Seattle, Wash. PARTICIPANTS: Two hundred patients receiving long-term warfarin therapy for various indications during April 3, 1990, to May 31, 2001. Only patients with a complete history of warfarin exposure were included. MAIN OUTCOME MEASURES: Anticoagulation status, measured by time to therapeutic international normalized ratio (INR), rate of above-range INRs, and time to stable warfarin dosing; and time to serious or life-threatening bleeding events. RESULTS: Among 185 patients with analyzable data, 58 (31.4%) had at least 1 variant CYP2C9 allele and 127 (68.6%) had the wild-type (*1/*1) genotype. Mean maintenance dose varied significantly among the 6 genotype groups (*1/*1 [n = 127], *1/*2 [n = 28], *1/*3 [n = 18], *2/*2 [n = 4], *2/*3 [n = 3], *3/*3 [n = 5]) (by Kruskall-Wallis test, chi(2)(5) = 37.348; P<.001). Compared with patients with the wild-type genotype, patients with at least 1 variant allele had an increased risk of above-range INRs (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.03-1.90). The variant group also required more time to achieve stable dosing (HR, 0.65; 95% CI, 0.45-0.94), with a median difference of 95 days (P =.004). In addition, although numbers were small for some genotypes, representing potentially unstable estimates, patients with a variant genotype had a significantly increased risk of a serious or life-threatening bleeding event (HR, 2.39; 95% CI, 1.18-4.86). CONCLUSIONS: The results of our study suggest that the CYP2C9*2 and CYP2C9*3 polymorphisms are associated with an increased risk of overanticoagulation and of bleeding events among patients in a warfarin anticoagulation clinic setting, although small numbers in some cases would suggest the need for caution in interpretation. Screening for CYP2C9 variants may allow clinicians to develop dosing protocols and surveillance techniques to reduce the risk of adverse drug reactions in patients receiving warfarin. 相似文献
10.
目的 探讨云贵高原汉族人群细胞色素P450 (CYP) 2C18、维生素K环氧化物还原酶复合体亚单位1(VKORC1)、CYP2C9的基因型分布情况及其基因多态性与华法林稳定剂量的相关性.方法 以2011年1月至2014年1月在该院行瓣膜置换术后持续服用华法林抗凝治疗的云贵高原汉族患者176例为研究对象,采集静脉血检测各位点基因型,分析基因型及等位基因频率分布,以及基因多态性与华法林稳定剂量的相关性.结果 各位点基因型及等位基因频率分布均符合Hardy-Winberg遗传平衡(P>0.05);CYP2C18(rs7896133)、VKORC1 (rs9923231)、CYP2C9(rs1057910)、CYP2C9 (rs4086116)基因位点的基因多态性与华法林稳定剂量相关(P<0.05).结论 云贵高原汉族患者CYP2C18(rs7896133)、VKORC1(rs9923231)、CYP2C9(rs1057910)、CYP2C9(rs4086116)基因多态性可能是华法林稳定剂量个体差异的影响因素. 相似文献
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目的:探讨不同CYP3A5基因型对肾移植术后患者血他克莫司浓度的影响,为肾移植术后患者他克莫司个体化治疗提供依据。方法:回顾性分析115例肾移植术后患者的临床资料,根据CYP3A5基因型分为野生纯合子组(CYP3A5*1/*1型,11例)、突变杂合子组(CYP3A5*1/*3型,46例)和突变纯合子组(CYP3A5*3/*3型,58例),记录3组患者术后不同时间点(7d、1个月、3个月、6个月、1年和2年)有效的血他克莫司浓度/剂量(C0/D)值。结果:3组患者体质量指数(BMI)、年龄构成比和性别构成比比较差异均无统计学意义(P>0.05)。与突变杂合子组比较,野生纯合子组患者术后7d、3个月、1年和2年他克莫司C0/D值明显降低(P=0.011,P<0.01,P=0.022,P=0.024);与突变纯合子组比较,野生纯合子组和突变杂合子组患者术后各个时段他克莫司C0/D值均明显降低(P<0.01)。野生纯合子组术后7d患者他克莫司C0/D值明显低于术后6个月、1年和2年(P=0.004,P=0.049,P=0.036);突变杂合子组术后7d患者他克莫司C0/D值明显低于术后1个月、3个月、6个月、1年和2年(P=0.006,P<0.01,P<0.01,P<0.01,P<0.01),术后1个月患者他克莫司C0/D值明显低于术后6个月(P=0.013);突变纯合子组术后7d患者他克莫司C0/D值明显低于术后1个月、3个月、6个月、1年和2年(P=0.002,P<0.01,P<0.01,P<0.01,P<0.01)。结论:CYP3A5基因多态性对肾移植术后患者血他克莫司浓度有明显影响,且这种影响可持续至术后2年。 相似文献
13.
目的了解江苏地区汉族人群中维生素K环氧化物还原酶亚单位1(VKORC1)、细胞色素P4502C9(CYP2C9)基因多态性分布、特点及与国外其他不同民族之间的差异。方法利用聚合酶链反应(PCR)和限制性内切酶片段长度多态性(RFLP)技术对206例江苏地区汉族人群中CYP2C9及VKORC1基因多态性进行检测,计算其基因型及等位基因频率,并与国外多个民族VKORC1、CYP2C9基因多态性分布进行比较。结果检测到VKORC1有A和G两种等位基因,A和G等位基因频率分别为0.91和0.09。VKORC1-1639G〉A基因型检测有169人为突变纯合子AA型,基因型频率为0.82,35人为杂合子GA型,基因型频率为0.17,2人为纯合子GG型,基因型频率为0.01。共检测到CYP2C9*1及CYP2C9*3两种等位基因,未检测到CYP2C9*2,CYP2C9*1及CYP2C9*3等位基因频率分别为0.95和0.05。CYP2C9基因型检测有186人为*1/*1型,基因型频率为0.90,20人为杂合子*1/*3型,基因型频率为0.1。结论江苏地区汉族人群中VKORC1、CYP2C9基因多态性分布有自己的特点,可为研究VKORC1、CYP2C9基因在中国汉族人群中华法林个体化用药提供理论依据。 相似文献
14.
Hua Xu Min Jiang Matt Oetjens Erica A Bowton Andrea H Ramirez Janina M Jeff Melissa A Basford Jill M Pulley James D Cowan Xiaoming Wang Marylyn D Ritchie Daniel R Masys Dan M Roden Dana C Crawford Joshua C Denny 《J Am Med Inform Assoc》2011,18(4):387-391
Objective
DNA biobanks linked to comprehensive electronic health records systems are potentially powerful resources for pharmacogenetic studies. This study sought to develop natural-language-processing algorithms to extract drug-dose information from clinical text, and to assess the capabilities of such tools to automate the data-extraction process for pharmacogenetic studies.Materials and methods
A manually validated warfarin pharmacogenetic study identified a cohort of 1125 patients with a stable warfarin dose, in which 776 patients were managed by Coumadin Clinic physicians, and the remaining 349 patients were managed by their providers. The authors developed two algorithms to extract weekly warfarin doses from both data sets: a regular expression-based program for semistructured Coumadin Clinic notes; and an advanced weekly dose calculator based on an existing medication information extraction system (MedEx) for narrative providers'' notes. The authors then conducted an association analysis between an automatically extracted stable weekly dose of warfarin and four genetic variants of VKORC1 and CYP2C9 genes. The performance of the weekly dose-extraction program was evaluated by comparing it with a gold standard containing manually curated weekly doses. Precision, recall, F-measure, and overall accuracy were reported. Associations between known variants in VKORC1 and CYP2C9 and warfarin stable weekly dose were performed with linear regression adjusted for age, gender, and body mass index.Results
The authors'' evaluation showed that the MedEx-based system could determine patients'' warfarin weekly doses with 99.7% recall, 90.8% precision, and 93.8% accuracy. Using the automatically extracted weekly doses of warfarin, the authors successfully replicated the previous known associations between warfarin stable dose and genetic variants in VKORC1 and CYP2C9. 相似文献15.
目的 探讨上海地区汉族人群中细胞色素氧化酶P450 2C9(CYP2C9)、维生素K环氧化物还原酶复合体1(VKORC1)基因多态性对华法林稳定剂量及华法林血浆浓度的影响.方法 纳入在体外循环下行瓣膜置换术且术后需服用华法林抗凝的患者226例,采用焦磷酸测序及UPLC/MS-MS法分别检测其CYP2C9和VKORC1基因型及其华法林血浆总浓度及游离浓度,分别以基因型、性别、年龄进行分组,比较不同组别患者华法林维持剂量和血浆浓度,并计算基因多态性及血药浓度、性别、年龄对华法林稳定剂量的贡献率.结果 CYP2C9 (1061A/C)基因型中,AA型患者华法林维持量高于AC型(P<0.05);VKORC1(-1639G/A)基因型中,AG型患者华法林维持量高于AA型患者(P<0.01);VKORC1 (1173C/T)基因型中,CT型患者华法林维持量高于TT型患者(P<0.01).CYP2C9(1061 A/C)不同基因型间其华法林血浆浓度差异无统计学意义,VKORC1(-1639G/A)不同基因型间及VKORC1 (1173C/T)不同基因型间华法林血浆浓度差异有统计学意义(P<0.01).男性患者所需华法林维持量高于女性患者(P<0.05),60岁以上患者所需华法林维持量低于60岁以下患者(P<0.05).CYP2C9(1061A/C)、VKORC1(-1639G/A)、VKORC1 (1173C/T)基因多态性及华法林血药浓度、年龄、性别分别解释了7.2%、29.1%、30.4%、6.7%、1.6%和1.4%的华法林个体剂量差异,多因素联合可解释47.2%的华法林个体剂量差异.结论 CYP2C9基因多态性与华法林抗凝药物剂量的个体间差异有关;VKORC1基因多态性与华法林抗凝药物剂量的个体间差异有关,且与其血药浓度密切相关.年龄和性别是影响华法林维持量的重要非基因因素. 相似文献
16.
目的研究云南汉族人群维生素K环氧化物还原酶复合体亚单位1基因VKORC1 1173C/T多态性分布及与其他群体间的差异,并探讨其与华法林抗凝维持剂量的分子遗传关系.方法采集300名心脏机械瓣膜置换术后服用华法林抗凝已达稳定剂量、凝血酶原时间国际标准化比值在目的范围(1.5~3.0)病人的外周血,采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)分析技术,检测VKORC1 1173C/T基因位点的基因型和等位基因频率,探讨华法林抗凝维持剂量与该基因多态性的关系.结果在所有的样本中,VKORC1 1173C/T基因共检出C(10%)和T(90%)2种等位基因,纯合子TT(80%)和杂合子CT(20%)两种基因型,云南汉族人群中VKORC1 1173C/T基因多态性分布在性别和年龄上无差异;CT基因型病人所需华法林维持剂量最高(3.62±1.35)mg/d,其次是TT基因型病人(3.12±1.17)mg/d.结论与其他群体相比,云南汉族人群VKORC11173C/T基因位点具有自己的遗传多态性,其基因型在华法林抗凝治疗中具有非常重要的意义. 相似文献
17.
目的 对CYP3A5基因多态性与他克莫司血药浓度的相关性进行分析,探讨其在临床肾移植患者个体化治疗中的应用意义。方法 选择2014年3月~2016年5月间,笔者医院收治的获得明确诊断、符合条件接受同种异体肾移植手术患者115例作为研究对象,对受试者展开CYP3A5基因型检测,而后对不同基因型患者的他克莫司血药浓度/剂量比值、急性排斥反应、不良反应的发生情况进行对比分析。结果 肾移植术后随访3个月,不同基因型者的他克莫司血药浓度/剂量比值差异有统计学意义,表现为*3/*3基因型患者最高(P<0.05);术后不良反应发生率比较发现,*3/*3基因型患者的发生率高于其他基因型(P<0.05);不同基因型患者术后急性排斥反应发生率比较,*1/*1型急性排斥反应发生率高于其他基因型(P<0.05)。结论 CYP3A5基因多态性会影响到应用他克莫司血药浓度/剂量比值,不同基因型的不良反应发生率不同,在今后的临床工作中,应对其给予足够的重视。 相似文献
18.
目的:探讨供、受者CYP3A4多态性对活体肝移植(LDLT)患儿术后1个月内他克莫司浓度/剂量比(C0/D)和个体内变异度(IPV)的影响。方法:收集77例活体肝移植患儿,化学发光免疫分析法测定他克莫司谷浓度(C0)。检测供、受者CYP3A4*18B基因型,根据患者至少携带一个CYP3A4*1基因将患者分为两组,即CYP3A4表达组(EX,CYP3A4*1/*1或CYP3A4*1/*18B)和CYP3A4非表达组(NEX,CYP3A4*18B/*18B)。分析CYP3A4*18B多态性对不同基因型患者他克莫司C0/D和IPV的影响。结果:对于供者CYP3A4多态性,CYP3A4表达组他克莫司C0/D在术后第1周(Z=-4.694,P<0.001)、第2周(Z=-4.469,P<0.01)和第3周(Z=-2.205,P<0.05)均显著低于CYP3A4非表达组;对于受者CYP3A4多态性,CYP3A4表达组他克莫司C0/D在术后第1周(Z=-4.976,P<0.001)和第2周(Z=-3.054,P<0.01)均显著低于CYP3A4非表达组。此外,供、受者CYP3A4表达组与CYP3A4非表达组他克莫司IPV均无差异(均P>0.05)。结论:CYP3A4多态性影响LDLT患儿术后早期他克莫司C0/D,对他克莫司IPV没有影响。 相似文献
19.
《中华医学杂志(英文版)》2012,125(23):4233-4238
Background Cyclosporin A (CsA) is a substrate of both cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp), some of the single nucleotide polymorphisms (SNPs) in these genes are associated with interindividual variations in CsA pharmacokinetics. We studied the influence of these SNPs on the incidence of rejection and CsA nephrotoxicity, as well as pneumonia within one year after renal transplant and post-transplantation diabetes mellitus (PTDM), in order to find whether genetic evaluation may help to identify patients at risk and to modulate CsA therapy to optimize graft and patient outcomes.
Methods A total of 208 renal transplant recipients receiving CsA were genotyped for ABCB1 (C1236T, G2677T/A, and C3435T), CYP3A4*1G, and CYP3A5*3 by direct sequencing method. Retrospective case control study was utilized to identify the association between CYP3A4*1G, CYP3A5*3, ABCB1 genetic polymorphisms and CsA-related outcomes.
Results The patients with a CYP3A4*1G/*1G genotype were found to have a higher incidence of acute rejection compared with those with CYP3A4*1/*1.
Conclusion CYP3A4*1G/*1G genotype predict increased risk of acute rejection, so genetic evaluation may partly help to identify patients at risk and to modulate CsA therapy to optimize graft and patient outcomes.
相似文献
20.
目的 了解CYP2C9和VKORC1基因单核苷酸多态性在云南汉族人群中的频率分布.方法 采用电化学基因传感器法对202例样本的CYP2C9(430C> T、1075A>C和1080C>G)位点及 VKORC1(-1639G>A和1173C> T)位点基因多态性进行检测,统计其等位基因频率和基因型频率,并与相关人群的基因多态性分布进行分析.结果 202份样本中共检测到CYP2C9*2位点C/C基因型202例(100.0%),等位基因C频率为100.0%;CYP2C9*3位点A/A基因型185例(91.6%),A/C基因型15例(7.4%),C/C基因型2例(1.0%),等位基因 A频率为95.3%,C为4.7%;CYP2C9*5位点C/C基因型202例(100.0%),等位基因 C 频率为100.0%;VKORC1的 -1639G > A 位点 A/A 基因型145例(71.8%),G/A 基因型57例(28.2%),等位基因A频率为85.9%,G为14.1%;1173C> T位点T/T基因型145例(71.8%),C/T基因型57例(28.2%),等位基因T频率为85.9%,C为14.1%.结论 云南汉族人群CYP2C9基因和我国其他地区汉族人群的分布一致;VKORC1基因与国外人群、我国汉族和部分少数民族的基因分布有较大区别. 相似文献