江苏省乙型肝炎病毒基因型分布与临床相关性

目的：了解江苏省乙型肝炎病毒（HBV）基因型分布及其临床相关性。方法：选择江苏省HBV-DNA阳性慢性HBV感染者215例，其中HBsAg携带者3例，急性乙型肝炎3例，慢性乙型肝炎166例（轻度80例、中度50例、重度36例）。肝硬化27例，原发型肝癌12例，重症肝炎4例，采用S区基因测序法检测HBV的基因型。结果：215例HBV-DNA阳性血清标本中，B基因型72例（33．5％），C基因型132例（61．4％），B＋C基因犁11例（5．1％）；未发现A、D、E、F、G、H型；C基因型肝癌＋肝硬化＋重症肝炎＋慢性乙肝（中度＋重度）显著高于B型与B＋C型（P〈0．05），C基因型的病程明显较B基因型和B＋C基因型长（F=17．615），γ-干扰素B基因型感染者的血清含量比C基因型和B＋C基因型感染者的血清含量显著高（F=13．652），S2＋S3＋S4方面C基因型比B基因型和B＋C基因型显著增多（P〈0．05），结论：江苏省存在HBV的B、C和B＋C三种基因型；以C基因型为江苏省优势毒株；并且C基因型病程长，肝纤维化程度明显，严重的肝病以及原发性肝癌的患者中所占比例显著高于其他基因型。     

中链酰基辅酶A脱氢酶缺乏症新生儿筛查及随访研究

目的 探讨中链酰基辅酶A脱氢酶缺乏症（MCADD）中国人群流行病学特征、表型、基因型及预后。方法 回顾性分析2009年1月至2018年6月期间经高效液相色谱串联质谱（HPLC-MS/MS）筛查并结合基因检测诊断为MCADD的新生儿资料。结果 2 674 835例接受筛查的新生儿中诊断MCADD的12例（1/222 902）。其中10例接受基因检测,发现ACADM基因16个突变位点的13种突变类型：7种为已报道突变（p.T150Rfs^*4、p.M1V、p.R206C、p.R294T、p.G310R、p.M328V、p.G362E）;5种新突变（p.N194D、p.A324P、p.N366S、c.118+3A > G、c.387+1del G）和1例11号外显子缺失,以p.T150Rfs^*4最常见（4/16）。ACADM基因突变位点检出率80%。未见表型-基因型相关性。确诊后给予饮食指导及对症治疗,随访4~82个月期间未见急性代谢失衡发作,除1例合并脑发育不良外均预后良好。结论 MCADD在中国南方人群相对罕见;p.T150Rfs^*4为中国人群热点突变;筛查阳性的病例建议联合辛酰基肉碱检测及基因判断。     

Prognostic predictive value of TLR4 polymorphisms in Han Chinese population with hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiac disease and is an important cause of sudden death in patients of all ages. The aim of this study was to find out whether Toll-like receptor-4 (TLR4) polymorphism is associated with HCM. To explore the association between TLR4 gene polymorphisms and HCM, 486 HCM patients and 214 healthy controls were enrolled in a case–control study of Chinese Han population. Two single nucleotide polymorphisms (SNPs) in the promoter region of TLR4 gene, ?728G > C (rs11536865) and ?2081G > A (rs10983755), were genotyped by PCR restriction fragment length polymorphism (PCR-RFLP). The associations between TLR4 SNPs and overall survival (OS) of HCM patients were analyzed by the Kaplan–Meier estimation method and Cox proportional hazards regression analysis. Serum TLR4 level was determined by ELISA. Our results showed that the C allelic frequency of ?728G > C and A allelic frequency of ?2081G > A were higher in HCM patients than those in controls (P < 0.001). The ratios of genotype frequencies for both SNPs were associated with HCM susceptibility under three genetic models (P < 0.01). Two SNPs were also associated with the OS in HCM patients (P < 0.001). The CC genotype of ?728G > C and AA genotype of ?2081G > A were associated with poor prognosis of HCM (P < 0.001). Moreover, HCM patients had a higher serum TLR4 level compared with the controls (242.6 pg/ml versus 135.7 pg/ml, P = 0.027). In addition, significant associations were observed between CC genotype of ?728G > C or AA genotype of ?2081G > A and plasma TLR4 level (P < 0.01). The results of this study indicated that TLR4 polymorphisms may be a genetic susceptibility factor for HCM in the Han Chinese population.     

Combining allele frequency uncertainty and population substructure corrections in forensic DNA calculations

In forensic DNA calculations of relatedness of individuals and in DNA mixture analyses, at least two sources of uncertainty are present concerning the allele frequencies used for evaluating genotype probabilities when evaluating likelihoods. They are: (i) imprecision in the estimates of the allele frequencies in the population by using an inevitably finite database of DNA profiles to estimate them; and (ii) the existence of population substructure. Green and Mortera [6] showed that these effects may be taken into account individually using a common Dirichlet model within a Bayesian network formulation, but that when taken in combination this is not the case; however they suggested an approximation that could be used. Here we develop a slightly different approximation that is shown to be exact in the case of a single individual. We demonstrate the numerical closeness of the approximation using a published database of allele counts, and illustrate the effect of incorporating the approximation into calculations of a recently published statistical model of DNA mixtures.     

云南楚雄丙型肝炎基因型分布的特点

目的了解楚雄地区丙型肝炎病毒基因型分布的地域特点。方法统计楚雄州医院2013年12月～2016年2月诊治的146例HCV-RNA阳性患者丙型肝炎基因分型相关资料。从PUBMED、CNKI查阅周边地区丙肝基因型资料作为对比。结果楚雄地区丙肝基因型:1型32例(21.92%),2型4例(2.74%),3型99例(67.81%),6型11例(7.53%),无4、5型。亚型:1a型1例(0.68%),1b型31例(21.23%),2a型4例(2.74%),3a型20例(13.70%),3b型78例(53.42%),3i型1例(0.68%),6a型1例(0.68%),6u型1例(0.68%),6v型2例(1.37%),6n型7例(4.79%)。结论楚雄地区的丙型肝炎基因型特点:基因型以3型及1型为主。亚型:以3b为主,其次为1b、3a。少见基因型3i、6a、6n、6u、6v也有分布。无4、5型。其分布与邻国、邻省不同,与云南省内3b为主的大趋势一致,但与各地州市也有区别。其分布特点与各自的传播路线、范围、入体途径、强度相关;不可避免受全球流行的大背景所影响。随着交通条件改善,楚雄在毒品运输中的地位由集散地或节点下降为过境通道,性传播渐取代毒品传播成为HCV传播的主要途径,并以此桥接普通人群,也因此形成其独特的基因分布。     

Hepatitis C virus genotype 6:Virology,epidemiology,genetic variation and clinical implication

Hepatitis C virus(HCV)is a serious public health problem affecting 170 million carriers worldwide.It is a leading cause of chronic hepatitis,cirrhosis,and liver cancer and is the primary cause for liver transplantation worldwide.HCV genotype 6(HCV-6)is restricted to South China,South-East Asia,and it is also occasionally found in migrant patients from endemic countries.HCV-6 has considerable genetic diversity with23 subtypes(a to w).Although direct sequencing followed by phylogenetic analysis is the gold standard for HCV-6 genotyping and subtyping,there are also now rapid genotyping tests available such as the reverse hybridization line probe assay(INNO-LiPAⅡ;Innogenetics,Zwijnaarde,Belgium).HCV-6 patients present with similar clinical manifestations as patients infected with other genotypes.Based on current evidence,the optimal treatment duration of HCV-6 with pegylated interferon/ribavirin should be 48 wk,although a shortened treatment duration of 24 wk could be sufficient in patients with low pretreatment viral load who achieve rapid virological response.In addition,the development of direct-acting antiviral agents is ongoing,and they give high response rate when combined with standard therapy.Herein,we review the epidemiology,classification,diagnosis and treatment as it pertain to HCV-6.     

Retrospective analysis of molecular biology mechanism of ABO blood group typing discrepancy among blood donors in Jinan blood station

BackgroundTo accurately identify ABO blood typing in pre-transfusion testing is very important to ensure blood transfusion safely, which is a major responsibility of blood station.MethodsEighty-one blood donors samples with ABO blood group typing discrepancy was collected among 61952 donor samples in our blood station from January 2019 to July 2020. Blood group serological method was used to detect ABO blood group. DNA Sequencing was used to determine the genotype. The antibody screening test detects antibodies other than ABO.ResultsIn total, 61,952 donor samples were analysed for ABO typing discrepancies. The incidence among blood donors was 0.13% (81/61952). The most common reason of ABO typing discrepancies was due to specific antibody or non-specific agglutination (54.32%, 44/81), mainly anti-M antibody, cold autoantibody, anti-D antibody, anti-N antibody and anti-Lea antibody. The major cause of forward typing discrepancies among blood donors was ABO subgroups (25.93%, 21/81), including 10 cases of A subtype (1 case of A2, 2 cases of A3, 2 cases of Ax, 3 cases of AxB, 1 case of Ael, 1 case of Ahm), 6 cases of B subtype (2 cases of B3, 1 case of Bel, 3 cases of AB3), 2 cases of B subtype (A), 1 case of cisAB, and 2 cases of acquired B. The serum antibody was weakened in 16 cases (19.75%).ConclusionsThe blood types should be correctly identified by combining serology with gene sequencing to ensure the safety of clinical blood transfusion, when the forward and reverse typing discrepancies among the blood donors.