目的:遗传性球形红细胞增多症(hereditary spherocytosis,HS)是最常见的遗传性红细胞膜缺陷病,主要表现为贫血、黄疸、脾大。由于部分患者临床表现不典型、家族史阴性,加上传统的实验室检查敏感性和特异性均较低,常导致漏诊、误诊。目...目的:遗传性球形红细胞增多症(hereditary spherocytosis,HS)是最常见的遗传性红细胞膜缺陷病,主要表现为贫血、黄疸、脾大。由于部分患者临床表现不典型、家族史阴性,加上传统的实验室检查敏感性和特异性均较低,常导致漏诊、误诊。目前已明确ANK1、SPTB、SPTA1、SLC4A1和EPB42基因突变可引起其对应的编码蛋白质缺失,进而导致红细胞膜缺陷。本研究旨在分析HS基因诊断的可行性和临床应用价值。方法:回顾性收集2018年1月至2021年9月中南大学湘雅二医院血液内科收治的26例中国湖南HS患者的资料,分析其临床表现和实验室检测结果。应用二代测序(next-generation sequencing,NGS)结合Sanger测序,检测HS致病基因突变和胆红素代谢调控关键酶尿苷二磷酸葡萄糖醛酸转移酶1家族多肽A1(uridine diphosphate-glucuronosyl transferase 1 family polypeptide A1,UGT1A1)变异。根据美国医学遗传学与基因组学学会(American College of Medical Genetics and Genomics,ACMG)发布的《序列变异解释的标准和指南》进行致病基因变异判读。分析不同基因变异类型患者的临床特征,并对其临床诊断和基因诊断进行对比分析。结果:在26例HS患者中,贫血23例、黄疸25例、脾大24例、胆石症14例;16例有家族史,10例无家族史;25例HS致病基因突变检测结果为阳性,1例阴性。19个家系共检出18个HS致病基因杂合变异,其中14个为致病性变异,1个可能致病性变异,3个意义未明变异。SPTB突变(12个)和ANK1突变(4个)最多。变异类型以无义突变为主(9个)。SPTB突变组与ANK1突变组相比,外周血红细胞参数及溶血指标的差异均无统计学意义(均P>0.05)。ANK1突变组切脾率高于SPTB突变组,差异有统计学意义(χ^(2)=6.970,P=0.014)。不同突变类型(无义突变、移码突变、剪接位点突变及错义突变)组间外周血红细胞参数及溶血指标差异亦均无统计学意义(均P>0.05)。临床确�展开更多
Background: Gilbert syndrome (GS) is characterized by an elevated serum bil-irubin due to a polymorphism in Uridine Diphosphate Glucuronosyl Transferase (UGT1A1) gene. Several studies have found high prevalence of Gil...Background: Gilbert syndrome (GS) is characterized by an elevated serum bil-irubin due to a polymorphism in Uridine Diphosphate Glucuronosyl Transferase (UGT1A1) gene. Several studies have found high prevalence of Gilbert Syn-drome in some Asian countries but still haven’t explored in Bangladesh. Aim of this study was to determine the allele frequencies of two different variants of UGT1A1 polymorphisms (UGT1A1 6 and UGT1A1 28) among Bangladeshi population. Materials and method: Total 150 unrelated volunteer from outpa-tient unit of the Central Hospital Limited, and Bangabandhu Sheikh Mujib Medical University, Dhaka were enrolled in this study. Peripheral blood was obtained from each subject and DNA extraction was done by Genomic DNA Isolation Kit. Polymorphisms of UGT1A1*6 (c.211G>A) was genotyped using the TaqMan Assay-on-Demand SNP Typing System and UGT1A1*28 (c.-53_-52TA) promoter repeat number polymorphism was determined by PCR method on an ABI PRISM 3130 Genetic Analyzer. Results: 57.3% of the study participants were male, mean age of them was 4.05 years. Minor allele fre-quency (MAF) was 0.442 (44.2%) for UGT1A1*28 and 0.047 (4.7%) for UGT1A1*6. Conclusion: This is the first ever study conducted among Bangla-deshi population to identify the Gilbert syndrome and found very high prevalence. Drugs those who are conjugated by UGT1A1 may lead to worse adverse event due to UGT1A1 polymorphism. Infants having decreased UGT1A1 enzyme activity develop neonatal jaundice and its further complication like Ker-nicterus. Higher incidence of Gilbert syndrome among Bangladeshi might be the alert for the clinicians treating neonatal jaundice.展开更多
文摘目的考察黄芩素在正常和溃疡性结肠炎大鼠肝、肠微粒体中的酶促反应动力学差异。方法采用3%葡聚糖硫酸钠连续自由饮用10 d,诱导溃疡性结肠炎大鼠模型,分别制备正常和溃疡性结肠炎大鼠肝、肠微粒体,通过建立大鼠肝、肠微粒体体外孵育体系对黄芩素代谢进行研究,采用HPLCDAD检测方法对代谢产物黄芩苷进行定量测定,应用Graph Pad Prism 5.0软件分析数据,对比黄芩素在正常和溃疡性结肠炎模型中的酶促反应动力学常数最大反应速率(Vmax)和米氏常数(Km)。结果黄芩素(5~150μmol·L^(-1))在正常和溃疡性结肠炎大鼠肝微粒体中的代谢属于经典的米氏方程,Km分别为(59.13±7.756)、(57.45±6.699)μmol·L^(-1),Vmax分别为(6.086±0.3234)、(7.447±0.347)μmol/(min·mg),而在肠微粒体中符合底物抑制动力学特征,抑制速率(Ki)分别为(166.4±58.31)、(141.7±41.17)μmol·L^(-1),Vmax分别为(4.130±0.6035)、(5.797±0.7903)μmol/(min·mg)。不管是正常组还是模型组,黄芩素在肝脏中的代谢速率要显著高于肠微粒体;与正常组相比,溃疡性结肠炎大鼠肝、肠微粒体中黄芩素葡萄糖醛酸化反应的速率显著升高,同时发现了黄芩素的一个新代谢产物,可能为黄芩苷的同分异构体。结论溃疡性结肠炎疾病状态能够显著升高葡萄糖醛酸化转移酶的活性,可能是导致黄芩苷在疾病状态下体内暴露强度增加的因素之一。
文摘目的:遗传性球形红细胞增多症(hereditary spherocytosis,HS)是最常见的遗传性红细胞膜缺陷病,主要表现为贫血、黄疸、脾大。由于部分患者临床表现不典型、家族史阴性,加上传统的实验室检查敏感性和特异性均较低,常导致漏诊、误诊。目前已明确ANK1、SPTB、SPTA1、SLC4A1和EPB42基因突变可引起其对应的编码蛋白质缺失,进而导致红细胞膜缺陷。本研究旨在分析HS基因诊断的可行性和临床应用价值。方法:回顾性收集2018年1月至2021年9月中南大学湘雅二医院血液内科收治的26例中国湖南HS患者的资料,分析其临床表现和实验室检测结果。应用二代测序(next-generation sequencing,NGS)结合Sanger测序,检测HS致病基因突变和胆红素代谢调控关键酶尿苷二磷酸葡萄糖醛酸转移酶1家族多肽A1(uridine diphosphate-glucuronosyl transferase 1 family polypeptide A1,UGT1A1)变异。根据美国医学遗传学与基因组学学会(American College of Medical Genetics and Genomics,ACMG)发布的《序列变异解释的标准和指南》进行致病基因变异判读。分析不同基因变异类型患者的临床特征,并对其临床诊断和基因诊断进行对比分析。结果:在26例HS患者中,贫血23例、黄疸25例、脾大24例、胆石症14例;16例有家族史,10例无家族史;25例HS致病基因突变检测结果为阳性,1例阴性。19个家系共检出18个HS致病基因杂合变异,其中14个为致病性变异,1个可能致病性变异,3个意义未明变异。SPTB突变(12个)和ANK1突变(4个)最多。变异类型以无义突变为主(9个)。SPTB突变组与ANK1突变组相比,外周血红细胞参数及溶血指标的差异均无统计学意义(均P>0.05)。ANK1突变组切脾率高于SPTB突变组,差异有统计学意义(χ^(2)=6.970,P=0.014)。不同突变类型(无义突变、移码突变、剪接位点突变及错义突变)组间外周血红细胞参数及溶血指标差异亦均无统计学意义(均P>0.05)。临床确�
文摘Background: Gilbert syndrome (GS) is characterized by an elevated serum bil-irubin due to a polymorphism in Uridine Diphosphate Glucuronosyl Transferase (UGT1A1) gene. Several studies have found high prevalence of Gilbert Syn-drome in some Asian countries but still haven’t explored in Bangladesh. Aim of this study was to determine the allele frequencies of two different variants of UGT1A1 polymorphisms (UGT1A1 6 and UGT1A1 28) among Bangladeshi population. Materials and method: Total 150 unrelated volunteer from outpa-tient unit of the Central Hospital Limited, and Bangabandhu Sheikh Mujib Medical University, Dhaka were enrolled in this study. Peripheral blood was obtained from each subject and DNA extraction was done by Genomic DNA Isolation Kit. Polymorphisms of UGT1A1*6 (c.211G>A) was genotyped using the TaqMan Assay-on-Demand SNP Typing System and UGT1A1*28 (c.-53_-52TA) promoter repeat number polymorphism was determined by PCR method on an ABI PRISM 3130 Genetic Analyzer. Results: 57.3% of the study participants were male, mean age of them was 4.05 years. Minor allele fre-quency (MAF) was 0.442 (44.2%) for UGT1A1*28 and 0.047 (4.7%) for UGT1A1*6. Conclusion: This is the first ever study conducted among Bangla-deshi population to identify the Gilbert syndrome and found very high prevalence. Drugs those who are conjugated by UGT1A1 may lead to worse adverse event due to UGT1A1 polymorphism. Infants having decreased UGT1A1 enzyme activity develop neonatal jaundice and its further complication like Ker-nicterus. Higher incidence of Gilbert syndrome among Bangladeshi might be the alert for the clinicians treating neonatal jaundice.
