中国3个地区汉族人群补体C6的遗传多态性研究

运用聚丙烯酰胺凝胶等电聚焦(PAGIF)和免疫吸引技术,研究了3个地区汉族人群的C6多态性。得到的基因频率如下:漳州市——C6*A:0.4634、C6*B:0.5000、C6*R:0.0366(C6*B2:0.0317);成都市——C6*A:0.4975,C6*B:0.4484,C6*R:0.0545(C6*B2:0.0395);哈尔滨市——C6*A:0.4708,C6*B:0.5219,C6*R:0.0073(C6*B2:0.0073)。蒙古人种的C6*A频率一般都低于0.5,高加索人种的C6*A频率一般都高于0.6。黑人则介于两者之间。蒙古人种与高加索人种的另一个区别在于前者的C6*B2频率在0.03到0.07之间,而后者几乎没有C6*B2。     

中国广东省四个民族C6别型遗传特点——附三个新的罕见变异型报道

应用等电聚焦-免疫印迹法调查了广东省四个民族(汉、苗、黎和回族)C6遗传多态性。广州地区汉族C6等位基因频率分别为:C6*A0.4225,C6*B0.5288,C6*B2 0.0387和C6*R(M91,M92,M11,B21)0.0100。海南岛三个少数民族C6遗传特点与广州汉族相似,均处于Hardy-Weinberg平衡状态。共发现五个罕见基因的杂合子,其中三个等位基因为首次报道。     

中国武汉地区汉族人补体第四成份(C4)的遗传多态现象

对神经氨酸酶处理去涎的血浆进行高压琼脂糖电泳后,分别应用免疫固定和溶血覆盖技术调查了我国武汉地区汉族180人的C4多态现象。在C4A座位发现5个变型:C4A4、3、2、1和91;在C4B座位发现6个变型:C4B 3、2、1、92、9W和96。两个座位均有静息等位基因(C4A~*QO和C4B~*QO)存在。它们相应的基因频率为:C4A~*4,0.014;3,0.633;2,0.192;1,0.011;91,0.003;QO,0.147;C4B~*3,0.006;2,0.127;1,0.751;92,0.041;9W,0.003;96,0.006;QO,0.0660单零C4A(c4A QO)表型个体占总体28.3％,单零C4B(C4B QO)占11.1％;纯合C4A缺乏(C4A QO,QO)和纯合C4B缺乏(C4BQO,QO)分别占0.56％。和1.11％卡方测验表明,C4A和C4B基因频率分别符合Hardy-Weinberg遗传平衡定律。     

广东汉族人群补体C2 , Bf, C4的遗传多态现象

对110例广东汉族人血清作了补体C2, Bf, C4的测定,其基因频率分V1为：C2*C'0.9500, C2*B: 0.0227,C2-,4:0182, C2*QO:O．0091;Bf*S：0．8364, Bf^`F:0．1409, Bf*S07：0．0091, Bf *S025： 0.009i,Bf*S055：0,0045; C4*A3：0.6327,C4*A4：0．1327,C4*_00：0．1020, C4*A5：0．0255 （一4*A2: 0·0918,C4*,41：0．0053;C4*B1：0．4569, C4*B2：0．4416, C4*QO:O．0558,C4*B5：0．0152,C4"}B96： 0.0152, C4*B3:0.0102, C4*B92:0.0051。木调查在我国首次发现一例C2*QO纯合子。     

两种构祀植物花药培养单倍体的诱导

对110例广东汉族人血清作了补体C2, Bf, C4的测定,其基因频率分V1为：C2*C'0.9500, C2*B: 0.0227,C2-,4:0182, C2*QO:O．0091;Bf*S：0．8364, Bf^`F:0．1409, Bf*S07：0．0091, Bf *S025： 0.009i,Bf*S055：0,0045; C4*A3：0.6327,C4*A4：0．1327,C4*_00：0．1020, C4*A5：0．0255 （一4*A2: 0·0918,C4*,41：0．0053;C4*B1：0．4569, C4*B2：0．4416, C4*QO:O．0558,C4*B5：0．0152,C4"}B96： 0.0152, C4*B3:0.0102, C4*B92:0.0051。木调查在我国首次发现一例C2*QO纯合子。     

武汉地区汉族人群补体第二成分（C2）的遗传多态现象

使用聚丙烯酰胺凝胶等电聚焦溶血覆盖技术,调查了武汉地区231例汉族人的C2多态现象。C2表型为C2C的216人,C2BC9人,C2AC5人,C2A1人。基因频率为:C2~*A 0.0151,C2~*B 0.0195, C2~*C 0.9654。     

4个HLA等位基因在5个民族中分布的多样性研究

应用ARMS-SSP结合的方法调查与AIDS相关的HLA等位基因,即HLA-A*02,B*35,B*27,B*57四个基因在五个民族群体（云南汉族、彝族、傣族、新疆维吾尔族、广西壮族）中的分布情况,并进行了相应的遗传学分析。结果显示,HLA-A*02在壮族和汉族中检出的阳性样本频率非常高,在另外几个民族中的分布频率偏低;B*35基因在各民族中分布差异不大;B*27在傣族中的分布频率较高,汉族、彝族和壮族中分布的频率差异不大;B*57则在各民族中的分布差异不大;保护性的等位基因即A*02,B*27,B*57的基因型频率在5个民族中有极显著的差异。此课题增进了对我国部分AIDS流行地区AIDS相关HLA等位基因型遗传背景的了解,是对HLA与AIDS相关性研究资料的有益补充。     

成都地区汉族人群α_2HS-糖蛋白和型特异成份的遗传多态性

用等电聚焦免疫固定技术,调查了成都地区汉族286份无血缘关系个体血清α_2 HS-糖蛋白和型特异成分的表型频率,求得基因频率为:AHSG*1=0.6958,AHSG*2=0.3042;GC*1F=0.4021,GC*1S=0.3182,GC*2=0.2745,GC*1A=0.0052。     

湖南地区HBV患者MHC-Ⅰ类链相关基因A第五外显子微卫星多态性研究

分别提取湖南汉族人群108例慢性乙肝病毒(hepatitis B virus,HBV)患者、96例HBV携带者和142例健康对照者外周血基因组DNA,利用聚合酶链反应和基因扫描技术分别对它们的主要组织相容性复合体Ⅰ类链相关A(major histocompatibility complex class Ⅰ chain related A,MICA)基因第5外显子进行微卫星多态性分析;应用DNA测序分析对不同的基因型进行验证,同时应用PCR/SSP技术进行MICA*Del检测,确定MICA基因第5外显子基因型.发现本研究的三组中分别检出A4、A5、A5.1、A6、A9五种等位基因,且以A5和A5.1为主;在HBV携带组和健康对照组中分别检出MICA* Del基因.结果同时显示慢性HBV患者组MICA*A5.1/A9基因型频率、慢性HBV患者组的MICA*A9等位基因频率、慢性HBV患者组MICA* A9表型频率和HBV携带组MICA*A5.1/A9基因型频率均低于相应的健康对照组;而湖南地区汉族人群HBV携带者和慢性HBV患者间的基因型频率、等位基因频率和表型频率无显著性差异;因而推测MICA*A5.1/A9基因型和MICA*A9等位基因可能是抗HBV感染的一种保护性等位基因.为今后进一步研究HBV的感染、预防和治疗提供参考依据.     

中国维、苗、瑶、壮四个少数民族补体C4的遗传多态现象的检测报告

使用国际第四届补体遗传学会议推荐的方法及薄层激光扫描技术,检测了我国维吾尔族、苗族、瑶族、壮族的补体组分4(C4)的多态性,并与我们以往检测过的汉族的C4多态性一起进行了比较。结果发现,在C4A座位上,以C4A3频率最高,以下在汉族、苗族、瑶族、壮族中依C4A2、Q0、4、1次序降低。在C4B座位上,频率最高的均为C4B1。其它基因频率的依次排列,汉与维为2、Q0、3,苗与壮为92、Q0、2、3,瑶为Q0、2、92等。民族间的差异比较集中地存在于C4A2、C4B2、C4AQ0、C4BQ0等4个基因。本文还对中国汉族、日本人、白种、黑种人群的C4同种异型差异进行了对比与讨论。     

HLA-B*2736等位基因的序列分析

使用FLOW-SSO、PCR-SSP以及测序等分型技术, 发现一个与HLA-B*270401基因相关的未知基因。设计基因特异性引物单独扩增B*27基因的外显子2-5, 包括内含子2-4, 并进行双向测序, 分析与B*270401基因序列的差异。该基因的扩增产物为1 815 bp。与B*270401相比在外显子3和4共有10个碱基的改变, 从而使相应氨基酸发生错义或同义突变。碱基634 A→C (密码子130丝氨酸→精氨酸); 670 A→T (密码子142苏氨酸→丝氨酸); 683 G→T (密码子146色氨酸→亮氨酸); 698 A→T (密码子151谷氨酸→缬氨酸); 774 G→C (密码子176谷氨酸→天冬氨酸); 776 C→A (密码子177苏氨酸→赖氨酸); 781 C→G (密码子179谷氨酰胺→谷氨酸); 789 G→T (密码子181丙氨酸同义突变); 1 438 C→T (密码子206甘氨酸同义突变); 1 449 G→C (密码子210甘氨酸→丙氨酸)。在IMGT/HLA数据库中B*27组只有3个基因（B*270502 / 2706 / 2732）提交了内含子序列。该未知基因的内含子2序列与B*2706相同, 显示了与B*27组基因的同源性, 但其同源性在内含子3、4均未得到支持, 与B*27组基因相比, 内含子3的第106个碱基C→G, 碱基168缺失, 碱基179 G→A, 碱基536 G→A; 内含子4中碱基82 T→C。但其内含子3、4序列却与B*070201完全相同。该基因序列已提交GenBank, 编号为被DQ915176, 被WHO确认为HLA-B*2736等位基因。     

Effect of genetic and coexisting polymorphisms on platelet response to clopidogrel in Chinese Han patients with acute coronary syndrome

Polymorphisms of CYP2C19 are associated with platelet response to clopidogrel. This study was conducted to evaluate the contribution of the previously identified polymorphisms to the response of clopidogrel in a cohort of Chinese Han patients. A total of 222 acute coronary syndrome patients undergoing percutaneous coronary intervention treated with clopidogrel were enrolled from September 2012 to June 2013. Residual platelet aggregations for all patients were measured by the VerifyNow P2Y12 system. Sixteen single-nucleotide polymorphisms among nine genes were genotyped including CYP2C19, ABCB1 and PON1. In this study, CYP2C19*2 and CYP2C19*17 were strongly associated with higher platelet aggregation and lower platelet aggregation to clopidogrel treatment, respectively (P<0.001). Patients with CYP2C19*2 allele had a higher risk of high on-treatment platelet reactivity than non carriers (adjusted OR, 5.434; 95% CI, 1.918–15.399, P=0.01). The coexistence of CYP2B6*9 (rs8192719) and P2Y12 (rs2046934) and the coexistence of CYP2B6*1B (rs7254579) and P2Y12 (rs2046934) were also associated with poor response to clopidogrel. No significant relation of CYP2C19*3 and other polymorphisms to the platelet aggregation was found. In conclusion, CYP2C19*2, CYP2C19*17 coexistence of CYP2B6*9 (rs8192719) and P2Y12 (rs2046934) and coexistence of CYP2B6*1B (rs7254579) and P2Y12 (rs2046934) were identified to be associated with response to clopidogrel treatment in Chinese Han patients.     

C6 polymorphism in Japanese: typing by agarose gel isoelectric focusing-immunofixation

Agarose gel isoelectric focusing was used to investigate the genetic polymorphism of the sixth component of complement (C6) in Japanese. C6 patterns were visualized by the immunofixation procedure. The allele frequencies calculated from 135 individuals were as follows: C6*A = 0.467, C6*B = 0.481, C6*B2 = 0.037, and C6*B3 = 0.015. It is suggested that C6*B3 is the fourth common allele characterizing the Japanese population.     

A systematic genetic polymorphism analysis of the CYP2C9 gene in four different geographical Han populations in mainland China

While many studies have been focused on CYP2C9*2 and *3 there was a lack of large full gene sequencing on CYP2C9, and this study was designed to fill this gap. We used direct sequencing to systematically screen genetic polymorphisms of the CYP2C9 gene including the 5' -flanking region (2kb), all exons and their adjoining intron regions and the 3' UTR in 400 unrelated healthy Chinese Han volunteers. A total of 27 different CYP2C9 polymorphisms were identified, 3 of which were novel, including one in intron 6, a synonymous variant (1137T>C, Tyr379Tyr), and a deletion mutation in the 3'UTR (1739-1740ATdel), which potentially influences the stability of CYP2C9 mRNA. We identified CYP2C9*1, *2, *3, *8, *11, and *31, of which alleles *8 was identified for the first time in Chinese population while *11 first in Asian. This is the first systematic screening of genetic polymorphisms of CYP2C9 in the Chinese Han population.     

五个汉族群体C7的遗传多态性

在国内首次用等电聚焦和酶连免疫标记方法调查哈尔滨、西安、成都、贵阳、漳州等五个汉族群体的补体第七成分(C7)的遗传多态性。结果表明,C7*1基因频率最高,在0.8152至0.9144之间。C7*2频率在四个亚群中为0.0528至0.0849,但在贵阳人群中高达0.1527,是目前世界上已观察到的最高值。C7*4频率在五个亚群中无显著差异,在0.0180至0.0402之间。没有观察到C7*4有由北方人群扩散到南方的明显趋势。在南方的三个汉族亚群中观察到在高加索人和日本人群中存在的C7*3基因。     

HLA class I,KIR, and genome-wide SNP diversity in the RV144 Thai phase 3 HIV vaccine clinical trial

RV144 is the first phase 3 HIV vaccine clinical trial to demonstrate efficacy. This study consisted of more than 8,000 individuals in each arm of the trial, representing the four major regions of Thailand. Human leukocyte antigen (HLA) class I and killer cell immunoglobulin-like receptor (KIR) genes, as well as 96 genome-wide ancestry informative markers (AIMs) were genotyped in 450 placebo HIV-1-uninfected individuals to identify the immunogenetic diversity and population structure of this cohort. High-resolution genotyping identified the common HLA alleles as A*02:03, A*02:07, A*11:01, A*24:02, A*24:07, A*33:03, B*13:01, B*15:02, B*18:01, B*40:01, B*44:03, B*46:01, B*58:01, C*01:02, C*03:02, C*03:04, C*07:01, C*07:02, C*07:04, and C*08:01. The most frequent three-loci haplotype was B*46:01-C*01:02-A*02:07. Framework genes KIR2DL4, 3DL2, and 3DL3 were present in all samples, and KIR2DL1, 2DL3, 3DL1, 2DS4, and 2DP1 occurred at frequencies greater than 90 %. The combined HLA and KIR profile suggests admixture with neighboring Asian populations. Principal component and correspondence analyses comparing the RV144 samples to the phase 3 International HapMap Project (HapMap3) populations using AIMs corroborated these findings. Structure analyses identified a distinct profile in the Thai population that did not match the Asian or other HapMap3 samples. This shows genetic variability unique to Thais in RV144, making it essential to take into account population stratification while performing genetic association studies. The overall analyses from all three genetic markers indicate that the RV144 samples are representative of the Thai population. This will inform subsequent host genetic analyses in the RV144 cohort and provide insight for future genetic association studies in the Thai population.