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1.
姚彩霞  邢后彬  徐霁 《安徽医药》2020,24(3):551-556
目的评价 ABCB1基因 G2677T/A多态性与血脂水平及他汀类药物降脂效应的相关性。方法检索 Pubmed、Cochrane Library、CNKI、VIP和万方数据库。采用 MINORS量表对纳入的研究进行文献质量评价。用 RevMan 5.3软件进行统计分析。结果共纳入 10项独立研究,累计病人数 3 088例。 Meta分析结果显示携带 2677GG基因型与 non?GG基因型、 G non?G基因型或 Non?G non?G基因型人群之间的血脂水平( TC、LDL?C、HDL?C及 TG)差异无统计学意义,亦未发现这些不同组别人群之间他汀类药物降脂效应差异有统计学意义。结论基于研究结果,尚不能认为 ABCB1基因 G2677T/A多态性与血脂水平及他汀类药物降脂效应存在相关性。  相似文献   

2.
目的探索MDR1C3435T基因多态性与芬太尼术后镇痛效应的关系。方法术后随访患者并记录芬太尼镇痛使用量及不良反应发生情况,采用聚合酶链反应一限制性片段长度多态性(eCR-RFLP)技术对129例患者进行基因分型,比较不同基因型间芬太尼镇痛效应的差异。结果129例患者中、CC型51例(39.5%)、CT型57例(44.2%)、111型21例(16.3%)。CT型、TT型患者24h芬太尼镇痛使用量显著低于CC型(P〈0.05),TT型患者48h芬太尼镇痛使用量显著低于CC型(P〈0.05),CT型与CC型48h芬太尼镇痛量、不同基因型组间不良反应发生率差异无统计学意义。结论MDR1C3435T与术后不良反应无相关性,但与芬太尼术后镇痛使用量具有相关性,该基因型可能成为疼痛个体化治疗的参考指标。  相似文献   

3.
目的:评价ATP结合盒B亚家族成员1转运蛋白(ABCB1)基因多态性(rs1045642)对阿片类药物术后镇痛效果及术后恶心呕吐发生情况的影响。方法:检索中英文数据库,纳入考察ABCB1 C3435T基因多态性和阿片类药物术后镇痛效果、不良反应相关性的研究。使用RevMan5.3软件进行Meta分析。结果:共纳入15篇文献,共计2 560例研究对象。结果显示,西方人群ABCB1 C3435T CC型阿片类药物消耗量与CT+TT型相比较,差异有显著性[SMD=0.31,95% CI(0.04,0.58),P=0.02],T等位基因携带者术后阿片类药物消耗量大。亚洲人ABCB1 C3435T CC型阿片类药物消耗量与CT+TT型相比较,差异无统计学意义[SMD=0.12,95% CI(-0.17,0.42),P=0.41]。结论:ABCB1 C3435T基因多态性与术后阿片类药物消耗量相关,携带T基因患者阿片类镇痛药物消耗量大,需要更多的镇痛药物,需要根据患者个体情况谨慎调整镇痛药物使用量。  相似文献   

4.
目的:研究高脂血症患者MDR1C3435T基因分布及其基因多态性对辛伐他汀稳态血药浓度及降脂疗效的影响。方法:115名高脂血症患者均给予每天20 mg的辛伐他汀治疗4周,在给药前及给药4周后取血样,采用PCR-RFLP(聚合酶链反应-限制性片段长度多态性分析)基因检测技术对MDR1C3435T等位基因进行分析,应用全自动生化分析仪和高效液相色谱仪分别测定血脂及辛伐他汀稳态血药浓度。结果:115名高脂血症患者MDR1C3435T基因型分布符合Hardy-Weinberg遗传平衡(P>0.05),MDR1C3435T等位基因突变率为40.87%。野生纯合子基因(CC)型组、突变杂合子(CT)型组、突变纯合子(TT)型组之间辛伐他汀稳态血药浓度及降脂疗效无统计学差异(P>0.05)。结论:未发现MDR1C3435T基因多态性对辛伐他汀稳态血药浓度及降脂疗效有明显影响。  相似文献   

5.
目的: 研究腺苷三磷酸结合盒转运体B1(ABCB1)基因编码区C1236T多态性与癫痫耐药的联系。方法: 在PubMed、Springlink、Web of Science、Cochrane Library和中国知网5个数据库检索有关ABCB1 C1236T多态性与癫痫耐药的病例对照试验。纳入文献的时间为建库至2021年1月。采用RevMan 5.0软件对所纳入的数据进行分析。结果: 共纳入24篇文献, 癫痫患者中耐药2 699例, 药物敏感3 941例。Meta分析结果显示总人群中, C1236T基因多态性与癫痫耐药之间无显著相关(P>0.05)。种族亚组分析显示, 亚洲和印度人群结果和总体人群一致。但高加索人群中, 等位基因模型下, ABCB1 C1236T与癫痫耐药具有相关性(OR=1.22, 95%CI: 1.02~1.47, P=0.03)。而突尼斯人群中, C1236T基因多态性与癫痫耐药在5种基因模型下均具有统计学意义: 等位基因模型(OR=0.50, 95%CI: 0.35~0.72, P=0.000 2);共显性基因模型CC/TT(OR=0.28, 95%CI: 0.13~0.59, P=0.000 8);共显性基因模型CT/TT(OR=0.40, 95%CI: 0.21~0.78, P=0.007);显性模型(OR=0.33, 95%CI: 0.18~0.62, P=0.000 5);隐性模型(OR=0.49, 95%CI: 0.27~0.88, P=0.02)。结论: ABCB1 C1236T基因多态性与癫痫耐药在总人群, 亚洲以及印度人群中未发现相关性, 但在高加索和突尼斯人群中可能具有相关性。未来仍需大样本、多中心、高质量的研究进一步证实其相关性。  相似文献   

6.
Gβ3基因C825T多态性与抗抑郁药的临床疗效   总被引:2,自引:0,他引:2  
目的:研究中国南京地区人群中Gβ3基因C825T多态性与抗抑郁药的临床疗效是否存在相关性。方法:采用聚合酶链式反应-限制性片段长度多态性分析(PCR-RFLP)技术对154例抑郁症患者和100例健康志愿者进行基因型分析;用HAMD评定抗抑郁药的疗效。结果:抑郁症患者Gβ3基因基因型频率(CC22.7%,CT31.8%,TT44.8%)等位基因频率(C38.6%,T61.4%);与正常对照组基因型频率(CC27.0%,CT51.0%,TT22.0%),等位基因频率(C52.5%,T47.5%)比较具有显著性差异(P<0.001,P<0.05);140例抗抑郁药显效者Gβ3基因型频率(CC20.7%,CT31.4%,TT47.9%),等位基因频率(C364%,T63.6%)和14例药物无效者基因型频率(CC42.9%,CT35.7%,TT21.4%),等位基因频率(C60.7%,T39.3%)比较有显著性差异(P<0.001,P<0.001);不同基因型抑郁症患者经4wk SSRI,SNRI类抗抑郁药治疗后,HAMD总分均显著下降,减分率有显著差异(CC与CT比较,P>0.05;CC与TT比较,P<0.01;CT与TT比较,P<0.05)。结论:在中国南京地区人群中Gβ3基因C825T多态性与抑郁症及抗抑郁药疗效有关。  相似文献   

7.
目的探讨中国汉族人中肾移植患者的多药耐药基因(MDR1)外显子exon12 C1236T、exon21 G2677T/A、exon26 C3435T的单核苷酸多态性对免疫抑制剂环孢素(CsA)药动学的影响。方法采用聚合酶联反应和限制性内切片段长度多态性(PCR-RFLP)的方法对89例肾移植术后的患者进行MDR1基因分型。单克隆抗体荧光免疫偏振法测定患者术后CsA的谷浓度(c0)及服药后2 h浓度(c2)。比较不同基因型之间CsA浓度剂量比值的差异。结果在89例肾移植患者中,等位基因1236T、2677T、2677A、3435T突变频率分别为66%、43%、18%和37%。肾移植术后1 mo内,G2677T/A基因多态性与CsA的药动学有相关性,2个等位基因都发生突变的患者,其剂量校正c0,在术后1~7 d、8~15 d和16~30 d比野生型分别提高51%(P=0.005)、32%(P=0.002)和63%(P<0.001)。在术后16~30 d,无论携带有1个或2个突变等位基因的患者,剂量校正c2都要比野生型患者高26%(P=0.007)和19%(P=0.041)。C1236T的剂量校正c0在术后8~15...  相似文献   

8.
目的 探讨成熟B细胞淋巴瘤患儿ABCB1 C3435T(CC型、CT型和TT型)基因多态性与大剂量甲氨蝶呤(HD-MTX)化疗后血药浓度和药品不良反应(ADR)的相关性。方法 回顾性收集本院2019年10月1日至2022年10月1日收治的行HD-MTX化疗且检测ABCB1 C3435T基因型并测定MTX血药浓度的成熟B细胞淋巴瘤患儿的病历资料,分析基因多态性与MTX血药浓度和ADR的关系。结果 共收集66例患者,其中男52例,女14例,平均年龄(7.46±3.09)岁(1.9~15.0岁)。HD-MTX化疗后常见ADR为中性粒细胞减少(98.48%)、贫血(89.39%)、血小板减少(77.27%)和黏膜损伤(53.03%)等。ABCB1 C3435T TT型比CC型的MTX 44 h血药浓度更高(P<0.05)。CT和TT型比CC型的黏膜损伤、呕吐和肝损伤发生率更高(P <0.05)。结论 ABCB1 C3435T基因多态性与成熟B细胞淋巴瘤患儿HD-MTX血药浓度水平及ADR(黏膜损伤、呕吐和肝损伤)可能有关。  相似文献   

9.
10.
目的:探讨MTHFR C677T与PAI-1 4G/5G基因多态性联合与山东地区人群缺血性脑卒中发生风险的关系。方法:回顾性收集济南市中心医院2016年6月至2020年1月入院并进行基因多态性检测的患者,本研究共纳入468例山东地区人群,其中292例伴有缺血性脑卒中定义为卒中组,176例无缺血性脑卒中定义为对照组。卒中...  相似文献   

11.
The multi-drug resistance 1 (MDR1) gene encodes for a P-glycoprotein (PGP), which acts as a gate-keeper against various kinds of xenobiotics. Several single nucleotide polymorphisms (SNPs) in the MDR1 gene that may influence PGP level and function have been identified. The aim of this study was to simultaneously analyze the three most important MDR1 SNPs, C3435T, G2677T/A and C1236T, in the Serbian population and to compare the results with those published for other ethnic groups. A group of 158 unrelated, healthy subjects was included in the present study. For determination of MDR1 SNPs, a multiplexed mutagenically separated PCR was performed. The genotype frequency of the analyzed MDR1 SNPs was as follows: 3435 nt - 0.19 (CC), 0.54 (CT) and 0.27 (TT); 2677 nt - 0.26 (GG), 0.52 (GT), 0.15 (TT), 0.03 (GA) and 0.064 (TA), and 1236 nt - 0.23 (CC), 0.61 (CT) and 0.16 (TT). Our results for the Serbian population could be relevant for further investigation of drugs that are substrates of PGPand for studies of interethnic diversity in MDR1 polymorphism frequency.  相似文献   

12.
AIMS: The aim of the study was to determine whether a correlation exists between MDR1 (ABCB1) gene polymorphisms at positions 3435 (C3435T) and 2677 (G2677T(A)) and the expression of human hepatic P-glycoprotein (P-gp). METHODS: P-gp protein expression in 26 human livers was assessed by Western blotting and ABCB1 mRNA expression was determined by real time RT-PCR. The C3435T and G2677T(A) polymorphisms were identified by RFLP and direct sequence analysis, respectively. RESULTS: The C and G allele frequencies for the C3435T and G2677T(A) polymorphisms were 0.48 and 0.79, respectively, and the genotypes were in Hardy-Weinberg equilibrium. There was a 200- and 20-fold variation in the expression of ABCB1 mRNA and Pgp protein expression, respectively. There were no differences in mRNA and protein expression identified amongst the different genotypes attributable to the C3435T and G2677T(A) polymorphisms in the ABCB1 gene. Exposure to a PXR ligand prior to death did not influence mRNA or protein expression. CONCLUSIONS: There is substantial variability in the expression of Pgp in human liver, but this is not due to the presence of C3435T and G2677T(A) polymorphisms in the ABCB1 gene, although our study is limited by a small sample size.  相似文献   

13.
Abstract

1.?The purpose of this study was to establish a population pharmacokinetic (PK) model of tacrolimus and evaluate the influence of clinical covariates, including the genetic polymorphisms of the cytochrome P450 3A5 gene (CYP3A5) and gene-encoding P-glycoprotein (ABCB1), on the PK parameters in Chinese adult liver transplant recipients.

2.?Details of drug dose, sampling times and concentrations were collected retrospectively from routine therapeutic drug monitoring data early after liver transplant. Tacrolimus PKs was studied by a non-linear mixed-effect modeling (NONMEM) method. CYP3A5 genotypes, ABCB1 C3435T and G2677T/A polymorphism and a number of clinical covariates were tested for their influence on TAC PKs.

3.?A one-compartment model with first-order absorption and elimination adequately described the data. Apparent clearance (CL/F) and apparent volumes of distribution (V/F) in final population model were 17.6?L/h and 225?L, respectively. The absorption rate constant (Ka) was fixed at 4.48?h?1. The inter-individual variability in CL/F and V/F was 53.9 and 68%, respectively. In the final model, CYP3A5 genotype, post-operative day, alanine aminotransferase, total bilirubin, hematocrit and blood urea nitrogen were found to significantly influence the CL/F, whereas POD and HB influence V/F.

4.?Population PK analysis of tacrolimus in Chinese adult liver transplant patients resulted in identification of the CYP3A5 genotype, POD, BUN, ALP, HCT, TBIL and HB as significant covariates on the PK parameters of tacrolimus.  相似文献   

14.
The objective of this study was to develop a real-time polymerase chain reaction (PCR) method to detect MDR1 (human multidrug resistance gene) single nucleotide polymorphisms (SNPs) C3435T and G2677T. C3435T and G2677T are linked to MDR1 *2, which is associated with enhanced efflux activity in vitro. Using the Smart Cycler, an allele-specific real-time PCR-based genotyping method was developed to detect C3435T and G2677T. The MDR1 genotype of human genomic DNA templates was determined by direct DNA sequencing. PCR reactions for genotyping C3435T and G2677T by using allele-specific primers were conducted in separate tubes. An additional nucleotide mismatch at the third position from the 3′ end of each allele-specific primer was used to abrogate nonspecific PCR amplification. The fluorescence emitted by SYBR Green I was monitored to detect formation of specific PCRproducts. PCR growth curves exceeding the threshold cycle were considered positive. Fluorescence melt-curve analysis was used to corroborate results from PCR growth curves. Using PCR growth curves, our assay accurately determined hetero- and homozygosity for C3435T and G2677T. Genotype assignments based on PCR growth curve, melt-curve analysis, agarose gel electrophoresis, and direct DNA sequencing results of PCR products were in perfect agreement. We have developed a rapid MDR1 genotyping method that can be used to assess the contribution of MDR1 *2 to pharmacokinetic and pharmacodynamic variability of P-glycoprotein substrates.  相似文献   

15.
The two most frequently observed single nucleotide polymorphisms (SNPs) of the human multidrug resistance 1 (MDR1) gene are 2677G/T/A (893Ala/Ser/Thr) and 3435C/T (no amino acid substitution). In this study, six forms of MDR1 cDNAs with the SNPs were expressed in LLC-PK1 cells and their transport activities were determined. Nearly identical amounts of the recombinant MDR1 proteins were expressed in the established cell lines using the Flp recombinase, which integrates a gene of interest at a specific genomic location. Four structurally diverse compounds: verapamil, digoxin, vinblastine and cyclosporin A, were examined for transcellular transport activities and intracellular accumulation. No significant differences were observed between cells expressing five polymorphic types of the MDR1 cDNAs (2677G/3435T, 2677A/3435C, 2677A/3435T, 2677T/3435C, 2677T/3435T) and cells expressing the wild-type (2677G/3435C). These results suggested that the two frequently observed MDR1 SNPs had no effect on the transport activities of MDR1 proteins expressed in LLC-PK1 cells in vitro, and other genetic or environmental factors might control the expression of MDR1 and the in vivo activity of MDR1.  相似文献   

16.
1. The purpose of the present study was to investigate the association between the single nucleotide polymorphism (SNP) 45T/G and plasma adiponectin levels and the prevalence of Type 2 diabetes mellitus (T2DM) in Uygurs of the Xinjiang region, China. 2. We performed a cross-sectional survey in a representative sample of 151 Uygur adults aged 24-80 years. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to determine the distribution of allele and genotype frequency of the SNP45 T/G polymorphism (exon 2) in the adiponectin gene. An ELISA was used to determine plasma adiponectin levels. Logistic regression was used to screen risk factors for T2DM. 3. Compared with the normal glucose tolerance (NGT) group, the T2DM group exhibited a higher distribution of the TG + GG genotype, G allele frequency and lower plasma adiponectin concentrations in TG + GG genotype carriers compared with those with the TT genotype. Compared with SNP45 T carriers, in the NGT group, G carriers had higher levels of systolic and diastolic blood pressure, low density lipoprotein (P < 0.05) and total cholesterol (P < 0.005). In the T2DM group, G carriers had lower levels of homeostasis model assessment (HOMA) of insulin sensitivity (P < 0.05) and higher levels of HOMA of insulin resistance (P < 0.05). 4. Adiponectin SNP 45 is positively correlated with the prevalence of T2DM in Uygurs of Xinjiang. The G allele carriers who have reduced plasma concentrations of adiponectin may have associated insulin resistance.  相似文献   

17.
Abstract

1. Familial Mediterranean fever (FMF) is considered an autosomal recessive disorder, associated with a single gene named Mediterranean fever (MEFV). The aim of this study was to perform genotyping and haplotyping analysis of the multidrug resistance (ATP-binding cassette, subfamily B, member 1 – ABCB1) gene in FMF patients.

2. Three ABCB1 gene polymorphisms (C1236T, G2677T/A and C3435T) were analyzed in 309 FMF patients and 250 healthy control subjects. All subjects were genotyped by PCR–restriction fragment length polymorphism analysis, and statistical analysis was performed using the Arlequin 3.1.1 and SPSS 16.0 software packages.

3. The CT genotype frequency of the C3435T polymorphism (p?=?0.003), the CT–GT–CT (C1236T–G2677T/A–C3435T) triple genotype (p?=?0.001) and the C–G (C1236T–G2677T/A) haplotype (p?=?0.030) were more common in the FMF patients. The CT–GG–CC triple genotype and T–G–C, C–T–T and T–G–T haplotypes (C1236T–G2677T/A–C3435T) were higher in the control subjects (p?=?0.011, 0.001, 0.009 and 0.000, respectively). The CT–GG binary genotype and C–T and T–G haplotypes for C1236T–G2677T/A polymorphisms may have a high degree of protective effect against FMF (p?=?0.0005, 0.002 and 0.000, respectively).

4. Our study showed that genotypes and haplotypes of ABCB1 gene polymorphisms may affect patients’ FMF susceptibility.  相似文献   

18.
Rationale  Aripiprazole acts as a partial agonist at dopamine D2 and D3 and serotonin 1A receptors and as an antagonist at serotonin 2A receptors (HTR2A). Since aripiprazole acts as an antagonist at HTR2A, genetic variants of HTR2A may be important in explaining variability in response to aripiprazole. Objectives  This study investigated whether the efficacy of aripiprazole can be predicted by functional HTR2A A-1438G/T102C polymorphisms (rs63311/rs6313) as modified by clinical factors in Han Chinese hospitalized patients with acutely exacerbated schizophrenia. Materials and methods  After hospitalization, the patients (n = 128) were given a 4-week course of aripiprazole. Patients were genotyped for HTR2A A-1438G/T102C polymorphisms via the restriction fragment length polymorphism method. Clinical factors such as gender, age, duration of illness, education level, diagnostic subtype, and medication dosage were noted as well. The researchers measured psychopathology biweekly, using the Positive and Negative Syndrome Scale (PANSS). A mixed model regression approach (SAS Proc MIXED) was used to analyze the effects of genetic and clinical factors on PANSS performance after aripiprazole treatment. Results  We found that the GG/CC genotype group of HTR2A A-1438G/T102C polymorphisms predicts poor aripiprazole response specifically for negative symptoms. In addition, the clinical factors, including dosage of aripiprazole, age, duration of illness, and diagnostic subtype, were found to influence PANSS performance after aripiprazole treatment. Conclusions  The data suggest HTR2A A-1438G/T102C polymorphisms may predict negative symptoms performance upon aripiprazole treatment in schizophrenic patients as modified by clinical factors.  相似文献   

19.
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。  相似文献   

20.

AIMS

The aim of the present study was to evaluate the impact of adiponectin allele T45G and C-11377G genetic polymorphisms on efficacy of rosiglitazone in Chinese patients with type 2 diabetes (T2D).

METHODS

Patients with T2D (n = 255) and 120 healthy volunteers were enrolled to identify 45T/G and –11377C/G genotypes by polymerase chain reaction-restriction fragment length polymorphism assay. Forty-two T2D patients with different 45T/G or –11377C/G genotypes received orally rosiglitazone as a single-dose therapy (4 mg day-1 p.o.) for 12 weeks. Serum triglyceride, fasting plasma glucose (FPG), postprandial plasma glucose (PPG), glycated hemoglobin, fasting serum insulin, postprandial serum insulin, total cholesterol, homeostasis model assessment for insulin resistance (HOMA-IR), low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol (HDL-c) and adiponectin concentration were determined before and after rosiglitazone treatment.

RESULTS

We showed an attenuated rosiglitazone effect in patients with –11377CG+GG heterozygote genotype on FPG, PPG, HOMA-IR compared with –11377CC homozygote genotype. However, we found an enhanced rosiglitazone effect on serum adiponectin concentration in patients with –11377CC homozygote genotype compared with –11377CG+GG heterozygote genotype (P = 0.000) and in patients with 45TG + GG heterozygote genotype compared with 45TT homozygote genotype (P = 0.018). Finally, our results showed that there was an enhanced effect in patients with –11377/45 CGTT diplotype compared with other discovered diplotypes on FPG (P = 0.001) and PPG (P = 0.003) after rosiglitazone treatment.

CONCLUSIONS

These data suggest that the adiponectin allele 45T/G and –11377C/G polymorphisms are significantly associated with the therapeutic efficacy of multiple-dose rosiglitazone in Chinese patients with T2D.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

  • Rosiglitazone is able to increase serum adiponectin levels significantly in Type 2 diabetic patients.
  • The role of genetic factors that determine the marked interindividual variability in glucose-lowering efficacy of rosiglitazone in Chinese patients is not known.
  • The current study was designed to evaluate the impact of the adiponectin common allele 45T/G and −11377C/G polymorphisms on the response to rosiglitazone monotherapy in Chinese patients with Type 2 diabetes (T2D).

WHAT THIS STUDY ADDS

  • The genetic polymorphisms of adiponectin alleles 45T/G and −11377C/G as well as their common diplotypes are significantly associated with an attenuated fasting plasma glucose, postprandial plasma glucose and homeostasis model assessment for insulin resistance as well as an enhanced adiponectin concentration in Chinese patients with T2D after rosiglitazone treatment.
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