HLA-A、B基因多态性与遵义地区汉族人群肾综合征出血热的相关性研究

目的 探讨HLA-A、B基因多态性与遵义地区汉族人群肾综合征出血热(HFRS)的关联性.方法 采用群体研究方法,应用聚合酶链反应-序列特异性引物(PCR-SSP)技术对100例肾综合征出血热患者和100例健康对照者进行HLA-A、B基因分型,比较其等位基因频率(GF),并计算其相对危险度(RR).结果 肾综合征出血热患者组中,HLA-A*31、B*58的等位基因的基因频率分别为4%、l2.5%,较健康对照组的0、5%明显增高,两组比较差异具有统计学意义(X2值分别为6.380和7.792,P<0.05,RR值分别为18.47、2.91);患者组中HLA-B*40等位基冈的基因频率(11%)显著低于健康对照组(19%),两者之问差异具有统计学意义(X2=6.095,P<0.01,RR值为0.47).结论 研究提示在遵义地区汉族人群中,初步认为HLA-A*31、B*58基因与HFRS呈正相关,HLA-B*40基因与HFRS呈负相关.     

麻风病与HLA-A、HLA-B、HLA-DRB1、HLA-DQ等位基因关联性分析

目的 探讨中国山东人群HLA-A、HLA-B、HLA-DRB1、HLA-DQ等位基因与麻风病的相关性.方法 采用序列特异性引物聚合酶链反应法(PCR-SSP)对40例麻风病患者及20例健康对照者进行HLA-A、B、DRB1、DQ等位基因分型,x2检验基因频率差异.结果 麻风病患者HLA-B*13(x2=7.067,P=0.008)、DQ*02(x2 =4.156,P=0.041)基因频率较健康对照组低,有统计学意义(P＜0.05).LL型麻风患者HLA-B* 13(x2=7.159,P=0.007)等位基因频率降低、HLA-DRB1*15(x2=4.073,P=0.044)等位基因频率升高,与健康对照组相比均具有统计学意义(P＜0.05).TT型麻风病患者HLA-B *40(P =0.037)、DQ *05(x2 =5.147,P=0.023)等位基因频率高于健康对照组,差异具有统计学意义(P＜0.05).结论 HLA-B * 13、DQ*02基因可能对麻风病易感性有拮抗作用,可能是保护基因;HLA-B* 13可能是LL型拮抗基因、DRB1*15可能是LL型的易感基因;HLA-B* 40、DQ *05可能是TT型的易感基因.     

山东地区汉族人群中HLA-A、-B、-DRB1等位基因与原因不明卵巢早衰相关性研究

目的探讨HLA-A,-B和-DRB1位点等位基因多态性与原因不明卵巢早衰(premature ovarian failure,POF)的相关性。方法利用毛细管电泳测序技术(Capillary Electrophoresis),对36例汉族原因不明POF患者进行HLA-A,-B,-DRB1基因分型,并以865例山东健康汉族个体造血干细胞分型资料作为对照,分析HLA等位基因频率在两组中的分布差异。结果 POF组中HLA-A*33、HLA-B*07、HLA-B*52和HLA-B*55等位基因频率显著高于对照组(P<0.05)。HLA-A*33的等位基因频率POF组为19.44%,而正常对照组为10.17%,RR=2.18;HLA-B*07的等位基因频率POF组为12.50%,而正常对照组为5.32%,RR=2.65;HLA-B*52的等位基因频率POF组为11.11%,而正常对照组为4.10%,RR=3.06;HLA-B*55的等位基因频率POF组为5.56%,而正常对照组为1.50%,RR=4.23。结论山东汉族人群中HLA-A*33、HLA-B*07、HLA-B*52和HLA-B*55等位基因可能是POF的易感基因。     

西藏门巴族人群HLA-A、B和DRB1基因座多态性

目的 分析西藏门巴族HLA-A、B和DRB1 3个基因座的遗传特征，并研究其民族起源。方法应用序列特异性寡核苷酸探针反向斑点杂交技术对西藏自治区门巴族居住区47名门巴族无关个体HLA-A、B和DRB1基因座进行分型。对门巴族和我国其他11个群体(民族)的HLA-DRB1基因频率采用Neighbor-Joining(NJ)方法进行聚类分析。结果 在西藏门巴族人群中HLA-A基因座共检出23个等位基因，其中HLA-A*1101，A*2402，A*02011，A*0206基因最常见；HLA-B基因座共检出39个等位基因，其中HLA-B*3802，B*4001，B*4002，B*51011基因最常见；HLA-DRB1基因座共检出33个等位基因，其中HLA-DRB1*12021，DRB1*0403，DRB1*0701，DRB1*1201基因最常见，频率最高的等位基因分别是HLA-A*1101(0．2128)，HLA-B*3802(0．1064)和HLA-DRB1*12021(0．0851)。结论 西藏门巴族人群HLA基因座具有高度遗传多态性，聚类分析门巴族与西藏藏族遗传关系较近。     

HLA-A、-B基因多态性与流行性出血热的相关性

目的 探讨HLA-A、-B等位基因与流行性出血热的相关性.方法 采用聚合酶链反应.序列特异性引物(PCR-SSP)技术,检测流行性出血热患者的HLA-A、-B等位基因.结果 与50例正常对照组比较,在50例出血热患者中HLA-A*31的基因频率明显增高,经统计学检测,两组差别具有显著性(RR=14.8,x2=4.388,P=0.036);患者组中HIA-B*40等位基因的基因频率显著低于健康对照组,两者之间差异具有显著性(RR=0.42,x2=3.895,P=0.048).结论 HLA-A*31、-B*40等位基因与流行性出血热具有相关性,A*31可能是其易感基因,B*40可能是保护基因.     

济南汉族人群HLA-A、B、DRB1等位基因高分辨多态性分析

目的 分析济南地区汉族人群人类白细胞抗原(human leukocyte antigens,HLA)-A、B、DRB1座位等位基因的高分辨多态性.方法 采用PCR-测序分型(PCR-sequence-based typing,PCR-SBT)对鲁南地区483名无血缘关系的汉族健康个体进行HLA-A、B、DRB1座位高分辨基因分型,采用Arlequin3.5软件计算等位基因频率、单倍型频率,并就常见等位基因与其他人群进行比较.结果 济南汉族HLA-A、B、DRB1座位分别检出27、56和41个等位基因,其中等位基因频率分布最高的分别是A* 11∶01 (0.1615)、B*13∶02(0.1163)和DRB1* 07∶01 (0.1763);最常见的A*-B*-DRB1*单倍型是A*30∶01-B* 13∶02-DRB1* 07∶01 (0.0867).结论 济南地区汉族人群HLA-A、B、DRB1等位基因和单倍型具有较高的多态性.     

河南地区汉族人群复发性流产患者HLA-DRB1、DQB1等位基因多态性的研究

目的探讨复发性流产易感性与人类白细胞抗原(HLA)DR、DQ区域基因多态性的关系。方法采用序列特异性引物聚合酶链反应(PCR-SSP),分析200例复发性流产患者(患者组)和200例无不良妊娠史正常妇女(对照组)的DRB1和DQB1基因型。结果患者组中的DQB1*03(39.25%)等位基因频率显著高于对照组(32.5%)(P=0.047<0.05,RR=1.208),DQB1*05(14%)等位基因频率较对照组显著降低(22.75%)(P=0.001<0.05,RR=0.615);患者组中DRB1*09(14%)等位基因频率显著高于对照组(9.25%)(P=0.036<0.05,RR=1.514),DRB1*12(8.5%)等位基因频率较对照组显著降低(14%)(P=0.014<0.05,RR=0.607)。结论河南地区汉族人群中DQB1*03、DRB1*09可能是复发性流产的易感基因,而DQB1*05、DRB1*12可能对复发性流产的发生有保护作用。     

原发性肾病综合征与HLA-A、HLA-B、HLA-DRB1基因相关性的研究

目的探讨HLA-A、HLA-B、HLA-DRB1位点基因与山西汉族激素抵抗肾病综合征(SRNS)的相关性。方法用聚合酶链反应序列特异性引物法,对30例SRNS患者(成人22例,儿童8例)和45例正常对照者进行了HLA-A、HLA-B、HLA-DRB1等位基因分型,并分析了A、B、DRB1基因在各组的分布。结果SRNS患者组HLA-B*15、B*44基因频率较正常对照组增高(P<0.05);成人SRNS患者组HLA-DRB1*07、B*44基因频率较正常对照组增高(P<0.05),成人SRNS患者组HLA-DRB1*15基因频率较正常对照组降低(P<0.05);儿童SRNS患者组HLA-DRB1*10基因频率较正常对照组增高(P<0.05)。结论SRNS发病可能与HLA-B*15、B*44基因有关,成人SRNS发病可能与HLA-DRB1*07、B*44基因有关,HLA-DRB1*15对成人SRNS发病可能有保护作用,儿童SRNS发病可能与HLA-DRB1*10基因有关;HLA与SRNS的相关性不仅与人种、国家和地区有关,还可能与发病年龄有关。     

山东省烟台和威海地区汉族HLA-A、B和DRB1等位基因多态性及遗传距离分析

目的 分析山东省烟台和威海地区汉族人群人类白细胞抗原(human leukocyte antigen,HLA)-A、B、DRB1等位基因的多态性分布特征,并探讨该人群与其他人群的亲缘关系.方法 应用聚合酶链反应-序列特异性寡核苷酸探针方法(polymerase chain reaction-sequence specific olignucleotide probe,PCR-SSOP)对山东省烟台和威海地区4062名无亲缘关系的汉族健康个体进行HLA-A、B、DRB1基因分型.采用Arlequin3.5软件计算HLA等位基因频率、单倍型频率和连锁不平衡参数,按内氏公式计算出不同人群之间的遗传距离,并利用Mega5.0软件构建系统发生树.结果 该人群HLA-A、B、DRB1等位基因分布均符合Hardy-Weinberg平衡(P＞0.1).3个基因座分别检出18、33和13个等位基因,其中等位基因频率分布最高的分别是A* 02 (0.2935)、B* 15 (0.1485)和DRB1* 15 (0.1621);最常见的单倍型为A* 30-B* 13-DRB1* 07(0.0649),A* 33-B* 58、A*66-DRB1* 13、B*08-DRB1* 03呈现最强的连锁不平衡;山东省烟台和威海汉族人群与吉林省汉族人群遗传距离最小,为0.0034.结论 山东省烟台和威海地区汉族人群HLA-A、B、DRB1等位基因和单倍型具有较高的遗传多态性,该人群与吉林汉族人群亲缘关系最近.     

河南省骨髓库汉族捐献者HLA-A、B、DR高分辨基因多态性调查分析

背景：2009年开始,中华骨髓库加大HLA高分检测的力度,可缩短配型检索周期,提高配型成功率。 目的：统计分析河南省骨髓捐献者HLA-A、B、DRB1高分辨基因多态性。 方法：河南省汉族造血干细胞志愿捐献者血样3 874人份,志愿捐献静脉血,EDTA抗凝。采用SSO HD 荧光微珠流式高分辨HLA-A、B、DRB1基因分型检测方法,对3 874份骨髓捐献志愿者血样进行高分辨分型检测,用PCR-SSP高分辨检测、SBT检测解决存在的模棱两可问题。等位基因计数法计算等位基因的基因频率。 结果与结论：共检出A 34个,B 84个,DRB1 50个,A位点基因频率处于前5位的有A*0201(0.160 9)、 A*1101(0.162 7)、 A*2402(0.160 2)、A*3001(0.080 8)、 A*3303(0.078 9);B位点处于前5位的是B*1302(0.077 7)、B*4001(0.072 2)、B*5101(0.062 8)、B*4601(0.061 2)和B*0702(0.050 7);DRB1位点处于前5位的是DRB1*1501(0.146 9)、DRB1*0901(0.131 8)、DRB1*0701(0.121 1)、DRB1*1202(0.061 2)、DRB1*0405(0.058 2)。     

Diversity of HLA-B17 alleles and haplotypes in East Asians and a novel Cw6 allele (Cw*0604) associated with B*5701

The distribution of HLA-B17 alleles and their association with HLA-A, -C and -DRB1 alleles were investigated in seven East Asian populations Japanese, South Korean, Chinese-Korean, Man, Northern Han, Mongolian and Buryat populations). The B17 alleles were identified from genomic DNA using group-specific polymerase chain reaction (PCR) followed by hybridization with sequence-specific oligonucleotide probes (SSOP). In all of these East Asian populations, except Japanese and Chinese-Koreans, B*5701 was detected and strongly associated with A*0101, Cw*0602 and DRB1*0701. In contrast, B*5801 was detected in all the seven populations and strongly associated with A*3303, Cw*0302, DRB1*0301 and DRB1*1302. The A*3303-Cw*0302-B*5801-DRB1*1302 haplotype was observed in South Korean, Chinese-Korean, Buryat and Japanese populations, while A*3303-Cw*0302-B*5801-DRB1*0301 was predominantly observed in the Mongolian population. A similar haplotype, A*0101-Cw*0302-B*5801-DRB1*1302, was observed in the Buryat population. A novel Cw6 allele, Cw*0604, was identified in the Man population. This Cw allele was observed on the haplotype A*0101-B*5701-DRB1*0701. Thus, we confirmed, at the sequence level, that the common haplotypes carrying B*5701 and B*5801 have been conserved and shared in East Asian populations.     

中国汉族人群供-受者HLA-A、B、Cw、DRB1和DQB1高分辨等位基因频率分布及错配比例的研究

目的 从基因高分辨水平,分析中国汉族人群供-受者人类白细胞抗原(human leukocyte antigens,HLA)-A、B、Cw、DRB1、DQB1各位点等位基因频率和分布的多态性;及供-受者等位基因匹配情况.方法 采用基因测序分型(sequence based typing,SBT)、序列特异性寡核苷酸探针法(sequence specific oligonueleotide probe,SSOP)和序列特异性引物法(sequence specific primer,SSP),对2540名中国汉族人的(其中1168名受者,1372名供者)DNA标本进行HLA高分辨基因分型,并作统计学处理.结果 2540份样本中共检测到44种HLA-A等位基因,频率高于0.05的A*1101、A*2402、A*0201、A*0207、A*3303、A*0206、A*3001共占80.4%;81种HLA-B等位基因,频率高于0.05的B*4001、B*4601、B*5801、B*1302、B*5101共占43.0%;44种HLA-Cw等位基因,频率高于0.05的Cw*0702、Cw*0102、Cw*0304、Cw*0801、Cw*0602、Cw*0303、Cw*0302、Cw*0401共占80.3%;61种HLA-DRB1等位基因,频率高于0.05的DRB1*0901、DRB1*1501、DRB1*1202、DRB1*0803、DRB1*0701、DRB1*0405、DRB1*0301、DRB1*1101共占70.1%;22种HLA-DQB1等位基因,频率高于0.05的DQB1*0301、DQB1*0303、DQB1*0601、DQB1*0602、DQB1*0202、DQB1*0302、DQB1*0401、DQB1*0502、DQB1*0201共占87.4%.这5个位点均处于杂合子缺失状态,其中A、B、DRB1位点符合HardyWeinberg平衡(Hardy-Weinberg equi1ibrium,HWE)(P＞0.05);Cw、DQB1位点偏离HWE(P＜0.05);排除个别基因型观察值与期望值偏差较大外,这5个位点均符合HWE.在供-受者数据的比较中,HLA全相合(10/10)的比例仅22.4%;单个等位基因错配(9/10)的比例为24.6%;两个等位基因错配(8/10)的比例为26.3%.结论 中国汉族人群高分辨水平HLA-A、B、Cw、DRB1,DQB1等位基因频率及分布特点,对非亲缘造血干细胞移植供者检索有重要参考价值;并为中华骨髓库数据入库和利用提供遗传学依据.

Abstract：

Objective To analyze the allele frequencies and polymorphism of human leukocyte antigens (HLA) -A, B, Cw, DRB1 and DQB1 between donors-recipients on high-resolution typing; and to analyze the matching and mismatching proportion between donors and recipients. Methods HLA highresolution types were determined by sequence based typing (SBT), sequence specific oligonucleotide probe (SSOP) and sequence specific primer (SSP) on 2540 unrelated Chinese Han individuals including 1168 recipients and 1372 donors, then statistical analyses were carried out. Results Forty-four HLA-A alleles were detected, and among them the frequencies of A * 1101, A * 2402, A * 0201, A * 0207, A * 3303, A *0206 and A * 3001 exceeded 0.05, and accounted for 80.4%. Eighty-one HLA-B alleles were detected, and frequencies of B * 4001, B * 4601, B * 5801, B * 1302 and B * 5101 exceeded 0. 05, and accounted for 43. 0% of total. There were 44 HLA- Cw alleles, among them the frequencies of Cw * 0702, Cw * 0102,Cw * 0304, Cw * 0801, Cw * 0602, Cw * 0303, Cw * 0302 and Cw * 0401 exceeded 0.05, and were 80.3 %of total. There were 61 HLA-DRB1 alleles, the frequencies of DRB1 * 0901, DRB1 * 1501, DRB1 * 1202,DRB1 * 0803, DRB1 * 0701, DRB1 * 0405, DRB1 * 0301 and DRB1 * 1101 exceeded 0. 05, and were 70. 1% of total. Finally, 22 HLA-DQB1 alleles were detected, the frequencies of DQB1 * 0301, DQB1 *0303, DQB1 * 0601, DQB1 * 0602, DQB1 * 0202, DQB1 * 0302, DQB1 * 0401, DQB1 * 0502 and DQB1 *0201 exceeded 0. 05, and they were 87.4% of total. All the five loci were of heterozygote deficiency. The HLA-A, B and DRB1 loci conformed to Hardy-Weinberg equilibrium (HWE) (P＞0. 05); but HLA-Cw and HLA-DQB1 loci did not (P＜0.05). Except several particular genotypes, all the five loci conformed to HWE. After comparing data between donors and recipients, only 22.4% of recipients found HLA matched donors (10/10); 24. 6% of recipients found single HLA allele mismatched donors (9/10); 26. 3% of recipients had two HLA alleles mismatched donors (8/10). Conclusion The characteristics of allele frequencies and polymorphism of HLA-A, B, Cw, DRB1 and DQB1 on high-resolution typing in Chinese Han population is valuable for donor searching in unrelated hematopoietic stem cell transplantation, and it provides genetic basis for donor registry and usage of donor resource for Chinese Marrow Donor Program.     

兰州地区汉族人群HLA-A、B和DRB1等位基因多态性分析

目的分析兰州地区汉族人群HLA-A、B和DRB1位点等位基因多态性特点。方法采用序列特异性引物聚合酶链反应技术对兰州地区200名健康无血缘关系的汉族个体HLA-A、B和DRB1基因座进行分型，并与西北、北方和南方汉族、西北回族、维吾尔族和藏族人群进行比较。结果兰州汉族人群中HLA-A基因座共检出14个等位基因，以A＊02，A＊11，A＊24，A＊33，A＊30，A＊01和A＊31基因最常见；HLA—B基因座共检出32个等位基因，以B＊40，B＊15，B＊46，B＊13，B＊51，B＊60，B＊58和B＊44基因最为常见；HLA-DRB1基因座共检出13个等位基因，最多见的基因依次为DRB1＊09．DRB＊15，DRB1＊12，DRB1＊04，DRB1＊11，DRB1＊07，DRB1＊08和DRB1＊14，接近北方汉族而与南方汉族有差异，与西北回族无明显差异，但与西北维吾尔族和藏族差异有统计学意义。结论兰州地区汉族人群HLA-A、B和DRB1位点等位基因多态性与南、北汉族人群存在不同程度的差异，与西北维吾尔族和藏族差异显著。     

应用SBT直接测序分型法研究中国南方汉族人群HLA五个基因座单倍型

目的 研究中国南方汉族人群HLA-A、B、Cw、DRBl、DQBl等位基因多态性及单倍型的分布特征.方法 应用聚合酶链反应-直接测序分型(polymerase chain reaction sequence-based typing,PCR-SBT)法对186名中国南方汉族健康人群HLA-A、B、Cw、DRBl、DQBl进行基因分型.结果 检出的HLA-A、B、Cw、DRBl、DQBl等位基因分别有28、49、24、29、20种.经统计分析A*0207-B*4601(10.81%),A*3303-B*5801(6.14%),B*4601-DRBl*0901(6.22%),B*4001*DRBl*0901(3.78%),DRBl*0901-DQBl*0303(12.16%)和DRBl*1202-DQBl*0301(8.38%)单倍型呈强连锁不平衡单倍型(RLF≥0.5,X<'2>>3.84,P<0.05);A*0207-B*4601-Cw*0102(10.75%),A*3303-B*5801-Cw*0302(5.14%),A*0207-B*4601-DR*0901(5.07%),A*3303-B*5801-DRBl*0301(2.96%),A*0207-B*4601-Cw*0102-DRBl*0901-DQBl*0303(4.87%)和A*1101-B*1301-Cw*0304-DRBl*1501-DQBl*0601(2.43%)单倍型分别是中国南方汉族人群常见单倍型.结论 中国南方汉族人群HLA 5个基因座单倍型分布具有高度的遗传多态性且有其自身分布特点.本研究获得的较完整的HLA 5个基因座单倍型分布数据,将为人类学、HLA疾病相关性和器官移植等研究提供遗传学参考数据.     

HLA-DRB1*10与中国人慢性乙肝关联

目的研究ＨＬＡ－ＤＲＢ１基因与乙肝的关联,探讨可能由病毒感染继发的自身免疫反应导致疾病发展的主要原因,为乙肝的病因学及预后估计提供免疫学方面的资料。方法在我国北方地区随机选择５４名慢性乙肝患者,用ＰＣＲ／ＳＳＰ方法进行ＨＬＡ－ＤＲＢ１等位基因分型,对照组为同地区９２名健康人。采用疾病和ＨＬＡ相关分析软件进行数据处理。结果病人组ＨＬＡ－ＤＲＢ１＊１０基因频率明显增高为２５．９％（ＲＲ＝１０．３８,Ｐｃ＝０．００１）,其它等位基因频率在实验组与对照组间差异无显著性。结论ＨＬＡ－ＤＲＢ１＊１０基因与中国北方人群慢性乙肝关联     

HLA class I (A, B, C) and class II (DRB1, DQA1, DQB1, DPB1) alleles and haplotypes in the Han from southern China

In this study, polymerase chain reaction-sequence-specific oligonucleotide prode (SSOP) typing results for the human leukocyte antigen (HLA) class I (A, B, and C) and class II (DRB1, DQA1, DQB1, and DPB1) loci in 264 individuals of the Han ethnic group from the Canton region of southern China are presented. The data are examined at the allele, genotype, and haplotype level. Common alleles at each of the loci are in keeping with those observed in similar populations, while the high-resolution typing methods used give additional details about allele frequency distributions not shown in previous studies. Twenty distinct alleles are seen at HLA-A in this population. The locus is dominated by the A*1101 allele, which is found here at a frequency of 0.266. The next three most common alleles, A*2402, A*3303, and A*0203, are each seen at frequencies of greater than 10%, and together, these four alleles account for roughly two-thirds of the total for HLA-A in this population. Fifty alleles are observed for HLA-B, 21 of which are singleton copies. The most common HLA-B alleles are B*4001 (f= 0.144), B*4601 (f= 0.119), B*5801 (f= 0.089), B*1301 (f= 0.068), B*1502 (f= 0.073), and B*3802 (f= 0.070). At the HLA-C locus, there are a total of 20 alleles. Four alleles (Cw*0702, Cw*0102, Cw*0801, and Cw*0304) are found at frequencies of greater than 10%, and together, these alleles comprise over 60% of the total. Overall, the class II loci are somewhat less diverse than class I. Twenty-eight distinct alleles are seen at DRB1, and the most common three, DRB1*0901, *1202, and *1501, are each seen at frequencies of greater than 10%. The DR4 lineage also shows extensive expansion in this population, with seven subtypes, representing one quarter of the diversity at this locus. Eight alleles are observed at DQA1; DQA1*0301 and 0102 are the most common alleles, with frequencies over 20%. The DQB1 locus is dominated by four alleles of the 03 lineage, which make up nearly half of the total. The two most common DQB1 alleles in this population are DQB1*0301 (f= 0.242) and DQB1*0303 (f= 0.15). Eighteen alleles are observed at DPB1; DPB1*0501 is the most common allele, with a frequency of 37%. The class I allele frequency distributions, expressed in terms of Watterson's (homozygosity) F-statistic, are all within expectations under neutrality, while there is evidence for balancing selection at DRB1, DQA1, and DQB1. Departures from Hardy-Weinberg expectations are observed for HLA-C and DRB1 in this population. Strong individual haplotypic associations are seen for all pairs of loci, and many of these occur at frequencies greater than 5%. In the class I region, several examples of HLA-B and -C loci in complete or near complete linkage disequilibrium (LD) are present, and the two most common, B*4601-Cw*0102 and B*5801-Cw*0302 account for more than 20% of the B-C haplotypes. Similarly, at class II, nearly all of the most common DR-DQ haplotypes are in nearly complete LD. The most common DRB1-DQB1 haplotypes are DRB1*0901-DQB1*0303 (f= 0.144) and DRB1*1202-DQB1*0301 (f= 0.131). The most common four locus class I and class II combined haplotypes are A*3303-B*5801-DRB1*0301-DPB1*0401 (f= 0.028) and A*0207-B*4601-DRB1*0901-DPB1*0501 (f= 0.026). The presentation of complete DNA typing for the class I loci and haplotype analysis in a large sample such as this can provide insights into the population history of the region and give useful data for HLA matching in transplantation and disease association studies in the Chinese population.     

The association between HLA class II haplotype with Graves' disease in Thai population

The distribution of HLA-DRB1, -DQA1 and -DQB1 alleles were analysed in 124 Graves' disease (GD) patients compared to 124 normal controls in order to identify the alleles/haplotypes associated with GD in Thai population. The DRB1*1602-DQA1*0102-DQB1*0502 haplotype was significantly increased in GD patients (P = 0.0209, OR = 2.55). DRB1*07-DQA1*0201-DQB1*0201 haplotype (P = 0.039, OR = 0.32) and HLA-DRB1*12-DQA1*0601-DQB1*0301 haplotype (P = 0.0025, OR = 0.28) were significantly decreased in GD patients. Interestingly, a protective DRB1*07 allele in Thai population lacks an arginine at position 74 similar to DRB1*0311 (a protective allele in Caucasians). A significant association of DRB1*1602-DQA1*0102-DQB1*0502 and HLA-DRB1*12-DQA1*0601-DQB1*0301 alleles and haplotypes with GD was recently reported in Korean but not in any Caucasian studies. Thus, DRB1*1602 allele and closely linked haplotype, DRB1*1602-DQA1*0102-DQB1*0502, might serve as a marker for genetic susceptibility to GD in Asian population.     

Immunogenetics of two new HLA alleles: A*0108 and B*4031

Two new alleles, HLA-A*0108 and B*4031, were identified in north-western European Caucasoid subjects. A*0108 differed from A*010101 by a single substitution (C to T) at position 216 in exon 3, resulting in an amino acid difference of Arg to Trp at position 163. It was present on a haplotype with B*1501/60/70/71; Cw*0303; DRB1*1301; DRB3*0202; DQA1*0103; DQB1*0603 and its product reacted as a normal HLA-A1 specificity. B*4031 differed from B*4001 by two nucleotides in exon 3 (positions 20 (G to C) and 69 (A to G)) resulting in two amino acid differences (Arg to Ser at position 97 and Asn to Asp at position 114). It was found on a haplotype with HLA-A*03; Cw*0304; DRB1*0404/32; DRB4*0101/3/5; DQA1*03; DQB1*0302 and has the HLA-B60 specificity. Both alleles have frequencies of < 0.0002 in the largely north-western European Caucasoid blood donor population resident in Wales.