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11.
目的探讨广西柳州三江县侗族新生儿UGT1A1基因变异特点及其与侗族新生儿高胆红素血症发生的关系。方法前瞻性选取2021年1月至2022年1月于三江县人民医院新生儿科诊断不明原因高胆红素血症的新生儿84例为研究对象;另选取同期健康新生儿60例纳入健康对照组。提取两组新生儿外周血基因组DNA,对UGT1A1启动子区TATA盒和外显子1进行PCR扩增并进行基因测序。结果病例组检测出33例G71R错义突变,突变率为39%,A等位基因频率(21%)显著高于健康对照组(10%)(P<0.05)。携带G71R错义突变基因型的侗族新生儿发生高胆红素血症的风险是携带野生型的健康新生儿的2.588倍(P<0.05)。Hardy-Weinberg遗传平衡检验结果提示两组新生儿UGT1A1 G71R位点基因型符合遗传平衡(P>0.05)。结论UGT1A1 G71R突变是三江县侗族新生儿高频基因变异类型,且G71R错义突变与侗族新生儿发生高胆红素血症相关。 相似文献
12.
N. Banawalikar S. Adiga U. Adiga V. Shenoy S. Kumari P. Shetty S. Shetty K.P. Sharmila 《Brazilian journal of medical and biological research》2021,54(9)
Pediatric epilepsy comprises chronic neurological disorders characterized by recurrent seizures. Sodium valproate is one of the common antiseizure medications used for treatment. Glucuronide conjugation is the major metabolic pathway of sodium valproate, carried out by the enzyme uridine 5′-diphosphate (UDP) glucuronosyl transferase (UGT) whose gene polymorphisms may alter the clinical outcome. The objective of this study was to assess the association between UGT1A6 genetic polymorphism and clinical outcome in terms of efficacy and tolerability in pediatric epileptic patients on sodium valproate monotherapy. Pediatric epileptic patients (n=65) aged 2-18 years receiving sodium valproate monotherapy for the past one month were included. Genetic polymorphism patterns of UGT1A6 (T19G, A541G, A552C) were evaluated by PCR-RFLP. Clinical outcome was seizure control during the 6 months observation period. Tolerability was measured by estimating the hepatic, renal, and other lab parameters. Out of 65 patients, TT (40%), TG (57%), and GG (3%) patterns were observed in UGT1A6 (T19G) gene, AA (51%), AG (40%), and GG (9%) in (A541G) gene, and AA (43%), AC (43%), and CC (14%) in (A552C) gene. No statistical difference in clinical outcome was found for different UGT1A6 genetic polymorphism patterns. We concluded that different patterns of UGT1A6 genetic polymorphism were not associated with the clinical outcome of sodium valproate in terms of efficacy and tolerability. Sodium valproate was well-tolerated among pediatric patients with epilepsy and can be used as an effective antiseizure medication. 相似文献
13.
目的 分析未结合型高胆红素血症患者尿苷二磷酸葡糖醛酸基转移酶1A1(uridine diphosphate glucuronosyltransferase 1A1,UGT1A1)基因的突变情况,并探讨突变与血清总胆红素的关系.方法 抽提患者外周血基因组DNA,扩增UGT1A1基因的编码序列及启动子区,对扩增产物进行测序以确定基因突变.结果 在61例未结合型高胆红素血症患者中,共发现46例存在UGT1A1基因的突变.突变可分为5种,依据频率高低依次为211G→A、TATAA盒TA插入、686C→A、1091C→T以及1352C→T.携带单一位点纯合突变合并其它位点杂合突变患者的血清胆红素水平明显高于单位点纯合突变或多位点杂合突变患者(P<0.05).综合UGT1A1基因突变与血清总胆红素水平,44例未结合型高胆红素血症患者被诊断为Gilbert综合征,2例被诊断为Ⅱ型Crigler-Najjar综合征.结论 患者血清总胆红素水平不仅与UGT1A1基因突变数量有关,而且与突变的杂合或纯合状态有关. 相似文献
14.
《Drug metabolism and pharmacokinetics》2020,35(4):397-400
UDP-glucuronosyltransferases (UGTs) are drug-metabolizing enzymes essential for the metabolism of endogenous substrates and xenobiotics. The cynomolgus macaque is a nonhuman primate species widely used in drug metabolism studies. The molecular characteristics of UGTs have been extensively investigated in humans, but they remain to be elucidated in cynomolgus macaques. In this study, cynomolgus macaque UGT3A1, UGT3A2, and UGT8A1 cDNAs were isolated and characterized. Amino acid sequences deduced from cynomolgus UGT3A1, UGT3A2, and UGT8A1 cDNAs were highly identical with their human orthologs (93, 96, and 99%, respectively) and were closely clustered in a phylogenetic tree. In the genome, cynomolgus UGT3A and UGT8A genes were located in the regions corresponding to those of their human orthologs. Among the 10 tissue types analyzed, expression of cynomolgus UGT3A1 and UGT3A2 mRNAs was detected in liver, kidney, and testis; the UGT3A1 and UGT3A2 mRNAs were most abundant in liver and testis, respectively. Cynomolgus UGT8A1 was most abundantly expressed in kidney, followed by brain, jejunum, and testis. These results suggest that cynomolgus UGT3As and UGT8A1 have molecular similarities to their human orthologs. 相似文献
15.
Keiko Minami Haruki Higashino Makoto Kataoka Kazutaka Togashi Kuninori Mutaguchi Shinji Yamashita 《Journal of pharmaceutical sciences》2019,108(8):2774-2780
This study aimed to kinetically analyze the nonlinear absorption and systemic exposure of telmisartan (TEL) after oral administration to rats by using a stable isotope-IV method. Rats were orally administered different dose of TEL, followed by the intravenous injection of 0.005 mg/kg of deuterium-labeled TEL (TEL-d3). Assuming that TEL-d3 shows same pharmacokinetic properties with TEL, systemic clearance (CLtot), oral bioavailability (Foral), and intestinal and hepatic availability (Fa*Fg, Fh) of TEL were calculated in each individual rat. AUCpo of TEL increased disproportionately with dose and showed a sigmoid-type relation, indicating the involvement of multi-nonlinear processes in oral absorption of TEL. Fa*Fg of TEL increased with dose at the low-dose range while decreased at the high-dose range. In contrast, Fh increased and CLtot decreased significantly in the middle range (2 to 6 mg/kg). As main factors of nonlinearity, saturations of solubility, efflux transport in the intestine, and the hepatic uptake of TEL were indicated. In conclusion, this study demonstrated a high possibility of a stable isotope-IV method to characterize complicated pharmacokinetic properties of oral drugs in animals, which can help to consider the future risks in their clinical use. 相似文献
16.
Scartozzi M Loretelli C Berardi R Pierantoni C Silva RR Mari D Giampieri R Faloppi L Pistelli M Maccaroni E Bittoni A Del Prete M Galizia E Cascinu S 《Digestive and liver disease》2012,44(1):74-79
Background
Retrospective analyses suggested that a pharmacogenetic approach may allow a tailored selection of chemotherapy for metastatic colorectal cancer.Aim
We conducted a phase II study of pharmacogenetic-selected first-line chemotherapy in elderly patients with advanced colorectal cancer, with the aim to improve efficacy and to reduce toxicity in this group of patients.Methods
24 patients were enrolled in this study. Chemotherapy regimen was prospectively assigned based on TS, DPD, ERCC-1 and UGT1A1 genotyping results. Twelve patients (50%) were treated with modified FOLFIRI, 11 patients (46%) with modified FOLFOX6 and 1 (4%) with De Gramont regimen.Results
A partial remission was obtained in 4 cases (17%), stable disease in 8 cases (33%) and progressive disease in 12 cases (50%). Grade 3-4 neutropenia was observed in 7 patients (29%) and diarrhoea in 3 cases (12%). The trial was then interrupted according to study design requiring 13 partial remissions out of the first 24 patients enrolled as the necessary response rate level in order to continue.Conclusion
Prospective selection of chemotherapy based on TS, DPD, ERCC-1 and UGT1A1 expression in elderly advanced colorectal cancer patients failed to confirm previous results. A more accurate validation of retrospective findings is warranted before these molecular markers can be used for treatment selection in the clinical practice. 相似文献17.
18.
Ji Ruan Yu‐Chen Yang Fu‐Quan Long Chang Sun 《Clinical and experimental pharmacology & physiology》2018,45(6):614-616
UGT2B10 is an important metabolism enzyme in human body and its substrates include multiple amine‐containing compounds, especially nicotine, tamoxifen and multiple antidepressants. Multiple common SNPs have been observed in its promoter region, but their role in expression regulation has never been investigated. In this preliminary study, we identified a novel cis‐regulatory SNP, rs294775, for UGT2B10 by plasmid construction, mutagenesis, and luciferase assay, whose mechanism was also investigated. Our work provides a basis for further pharmacogenetics study. 相似文献
19.
目的:检测和分析消化系统恶性肿瘤患者UGT1A1*6、UGT1A1*28基因多态性。方法:收集186例消化系统恶性肿瘤患者血液标本,采用焦磷酸测序方法对UGT1A1*6、UGT1A1*28基因多态性进行检测,并对基因多态性频率进行统计分析。结果:186例消化系统恶性肿瘤患者样本具有群体代表性。UGT1A1*6基因多态性为野生型G/G占比63.4%、杂合型G/A占比32.8%、突变纯合型AA占比3.8%;UGT1A1*28基因多态性为野生型TA6/TA6占比75.8%、杂合型TA6/TA7占比21.5%、突变纯合型TA7/TA7占比2.7%;UGT1A1*6和*28基因多态性为野生型G/G且TA6/TA6占比48.9%,单点变异型G/G且TA6/TA7占比12.4%、G/A且TA6/TA6占比23.1%,双点变异型G/G且TA7/TA7占比2.2%、G/A且TA6/TA7占比9.1%、A/A且TA6/TA6占比3.8%,三点变异型G/A且TA7/TA7占比0.5%。患者UGT1A1*6与UGT1A1*28基因多态性频率分布之间具有显著性差异(P<0.05)。3个不同年龄段患者之间,胃癌、结直肠癌、其他消化系统恶性肿瘤患者之间的UGT1A1*28、UGT1A1*6和*28基因型分布具有显著性差异(P<0.05)。结论:消化系统恶性肿瘤患者应用伊立替康时,应联合检测UGT1A1*6和UGT1A1*28基因多态性,同时密切关注患者的肿瘤类型以及年龄差异。 相似文献
20.