HLA—DQA1,DQB1,DRB1＊02,07,09等位基因及单倍型在华东地区汉？…

应用ＰＣＲ－ＳＳＯ方法，对华东地区汉族人群进行了ＨＬＡ－ＤＱＡ１，ＤＱＢ１和ＤＲＢ１＊０２，０７，０９基因分型，ＤＱＡ１中以ＤＱＡ１＊０３０１基因频率最高，其次为＊０５０１和０１０２，＊０４０１最低，ＤＱＢ１中以ＤＱＢ１＊０３０３频率最高，其次为＊０．３０１，＊０６０１和＊０２０１，＊０５０１，＊０６０４和＊０６０５最低；ＤＲ９基因频率较高，ＤＲ２中ＤＲＢ１＊１５０１占７３５，基因频率为０．０８５     

中国南方汉族人群HLA—DQB1基因对系统红斑狼疮的易感性研究

应用ＰＣＲ－ＲＦＬＰ核苷酸分型方法，探讨了我国南方浙江沪汉族人群ＨＬＡ－ＤＱＢ１基因多态性与系统红斑狼疮（ＳＬＥ）的遗传关联性，对４８例ＳＬＥ患者的血样分析表明，ＳＬＥ患者具有显著高的ＤＱＢ１＊０６０１等位基因频率（３０．２１％，ＲＲ＝２．８９１９，Ｐｃａｒｒ＝０．０１１２，ＥＦ＝０．２０），ＤＱＢ１＊０６０１可能是一易感基因，而ＤＱＢ１＊０３０１（２．０８％，ＲＲ＝０．１１０８，Ｐｃｏｒｒ＝０，     

用PCR—SSP方法研究广西壮族HIL—DQA1和B1基因多态性

目的 检测广西壮族ＨＬＡ－ＤＱＡ１，Ｂ１基因的多态性。方法 应用ＰＣＲ－ＳＳＰ方法对１４０名健康、无血缘关系广西壮族人的ＨＬＡ－ＤＱＡ１和ＤＱＢ１进行基因分型。结果 共检出７个ＤＱＡ１等位基因和１６个ＤＱＢ１等位基因。在检出的ＤＱＡ１等位基因中，０３０１的基因频率最高（３５％），０４０１的基因频率最低（１．１％）。在ＤＱＢ１等基因中，０６０１（２２．１％），０３０１（２０．７％），０５０１（１３．     

用PCR—RFLP方法研究新疆地区汉族HLA—DQA1和—DQB1基因多态性

应用ＰＣＲ－ＲＦＬＰ技术，对新疆地区汉族健康群体进行了ＨＬＡ－ＤＱＡ１（４９人）和ＤＱＢ１（４７人）基因分型。在ＤＱＡ１１８个等位基因中，ＤＱＡ１＊０３０１的基因频率最高（３２．５６％），＊０４０１最低（１．０２％）。在ＤＱＢ１１６个等位基因中，ＤＱＢ１＊０２０１（２０．２１％），＊０３０１（１５．９６％）、＊０３０３（１４．８９％）为最常见；没有观察到＊０５０３２、＊０５０４和＊０６０５。与河北     

用PCR-SSP方法研究广西壮族HLA-DQA1和B1基因多态性

目的　检测广西壮族ＨＬＡＤＱＡ１ ,Ｂ１ 基因的多态性。方法　应用ＰＣＲＳＳＰ 方法对１４０ 名健康、无血缘关系广西壮族人的ＨＬＡＤＱＡ１ 和ＤＱＢ１ 进行基因分型。结果　共检出７ 个ＤＱＡ１ 等位基因和１６ 个ＤＱＢ１ 等位基因。在检出的ＤＱＡ１ 等位基因中,０３０１ 的基因频率最高（３５ ％ ） ,０４０１ 的基因频率最低（１ ．１ ％ ） 。在ＤＱＢ１ 等位基因中,０６０１（２２ ．１ ％ ） ,０３０１（２０ ．７ ％ ） ,０５０１（１３ ．９ ％ ） 最为常见。未检出的等位基因包括ＨＬＡＤＱＡ１ ＊ ０２０１ ,０３０２ ,０６０１ ,ＤＱＢ１ ＊ ０６０３ ,０６０５ 和０６０８ 。结论　广西壮族ＨＬＡＤＱＡ１ ,Ｂ１ 基因的多态性不仅有中华民族的特点,而且也有其独特性。     

江浙沪地区HLA-DQB1基因对重症肌无力的遗传易感性研究

探讨中国汉人ＭＧ易感性与ＨＬＡ－ＤＱＢ１基因多态性的相关。方法：运用ＰＣＲ－ＲＦＬＰ法进行ＨＬＡ－ＤＱＢ１基因分型。结果：ＭＧ病例组与对照组比较都有ＤＱＢ＊０３０３频率的明显增高,ＤＱＢ＊０６０１和ＤＱＢ１＊０．６０２频率的明显降低,差异都有显著性。结论：ＤＱＢ１＊０３０３参与中国汉人ＭＧ的易感性,而ＤＱＢ１＊０６０１和ＤＱＢ１＊０６０２是保护基因。     

抗磷脂抗体阳性SLE患者HLA DRB1、DQA1、DQB1基因单倍型研究

本文采用ＰＣＲ ＲＦＬＰ技术对抗磷脂抗体阳性（ＡＰＡ＋）ＳＬＥ患者ＨＬＡ ＤＲＢ１、ＤＱＡ１ 和ＤＱＢ１ 基因进行分型研究, 同时以上海地区汉族随机人群作对照, 发现这类病人的ＤＲＢ１＊ ０８０３ ＤＱＡ１＊ ０１０３ ＤＱＢ１ ＊０６０１ 单倍型频率显著增高（ Ｐ＜ ０－０１） 相对危险率为４－４５, 说明该疾病与此单倍型存在着很强的关联。     

江浙沪地区汉人HLA－DQA1基因对重症肌无力的遗传易感性研究

采用一种新的多聚酶链反应－限制性片段长度多态性（ＰＣＲ－ＲＦＬＰ）基因分型法，研究了江浙沪地区中国汉人重症肌无力（ｍｙａｓｔｈｅｎｉａｇｒａｖｉｓ，ＭＧ）４５例和对照组９８例的ＨＬＡ－ＤＱＡ１等位基因。发现ＭＧ的胸腺瘤型和非胸腺瘤型ＤＱＡ１基因遗传背景有所不同，ＨＬＡ－ＤＱＡ１＊０３０１基因参与非胸腺瘤型ＭＧ（尤其是男性组）的遗传易感作用（ＲＲ＝３．６３，Ｐ＜０．０５），家系分析支持群体研究结果。推测了中国汉人ＭＧ可能的ＨＬＡ易感单体型：ＤＱＡ１＊０３０１ＤＱＢ１＊０３０３－ＤＲＢ１＊０９０１和ＤＱＡ１＊０３０１－ＤＱＢ１＊０３０３－ＤＲＢ１＊０４０６．结果从基因分型的角度统一了关于华人ＭＧ与ＨＬＡ相关抗原提法不一致的报道，并揭示了ＭＧ的其它ＨＬＡⅡ系统易感基因ＤＱＢ１＊０３０１、ＤＲＢ１＊０９０１及ＤＲＢ１＊０４０６或ＤＢＲ＊０４０５存在的极大可能性。为进一步分析ＭＧ的遗传易感机理提供了重要依据。     

胰岛素依赖型糖尿病患者的HLA－DQA_1等位基因分析

应用聚合酶链反应与序列特异寡核苷酸探针杂交技术（ＰＣＲ／ＳＳＯＰ），分析了北京地区６１例汉族胰岛素依赖型糖尿病（ＩＤＤＭ）患者和５０例非糖尿病对照者的ＨＬＡ－ＤＱα链第５２位氨基酸的编码基因。结果表明：１．８９％的患者ＨＬＡ－ＤＱα链５２位是精氨酸，其编码基因为ＨＬＡ－ＤＱＡ１０３０１和（或）０５０１，其中１０８％为０３０１纯合子，７０．３％为０３０１杂合子，１８．９％为０５０１纯合子，２．患者中的ＨＬＡ－ＤＱＡ１０３０１和０５０１等位基因频率较对照组明显升高，相对危险度分别为ＲＲ＝１２．５４９，ｐ＜０．００１和ＲＲ＝１．５１０，ｐ＞０．０５；３．患者中ＨＬＡ－ＤＱＡ０２０１等位基因频率较对照组无明显降低。上述结果提示，ＨＬＡ－ＤＱＡ１０３０１和０５０１等位基因与中国汉族人群的ＩＤＤＭ遗传易感性正相关，而０２０１等位基因与ＩＤＤＭ抗性无关。     

用PCR－RFLP方法研究新疆地区汉族HLA－DQA1和－DQB1基因多态性

应用ＰＣＲ－ＲＦＬＰ技术，对新疆地区汉族健康群体进行了ＨＬＡ－ＤＱＡ１（４９人）和－ＤＱＢ１（４７人）基因分型。在ＤＱＡ１８个等位基因中，ＤＱＡ１０３０１的基因频率最高（３２．５６％），０４０１最低（１．０２％）。在ＤＱＢ１１６个等位基因中，ＤＱＢ１０２０１（２０．２１％）、０３０１（１５．９６％）、０３０３（１４．８９％）为最常见；没有观察到０５０３２、０５０４和０６０５。与河北固安县及江浙沪地区汉族群体进行比较，ＤＱＡ１基因未发现存在差异。而ＤＢ１０６０２（３．１９％）与固安汉族（Ｐｃ＝０．０１４４）和上海汉族（Ｐｃ＝０．０１４０）有显著差异，ＤＱＢ１０５０３（８．５２％）与上海汉族有显著差异（Ｐｃ＝０．０２１６）。     

系统性红斑狼疮临床表现与HLA Ⅱ类单倍型关联的研究

目的 探讨系统性红斑狼疮（ＳＬＥ）易感基因致病的模式。方法 利用多聚酶链反应／特异寡核控针杂交（ＰＣＲ／ＳＳＯＰＨ）方法检测１１３例确诊ＳＬＥ病人的ＨＬＡⅡ基因型并进行单倍型分析。结果 ＳＬＦ病人的单倍型具有特定的结构特征,即以２个或３个重型ＳＬＥ相关基因共同组成１个单倍型;反之,２个或３个轻型ＳＬＥ相关基因组成另１个单倍型;重型基因和轻型基因之间很少有强连锁不平衡。ＤＱＡ１＊０３０１－ＤＱＢ１＊     

用聚合酶链反应-直接测序分型法研究江苏汉族人群HLA-DQA1和DQB1基因多态性

目的检测江苏地区汉族人群HLA-DQA1和DQB1等位基因及单倍型的频率，分析该人群DQA1、DQB1基因多态性和DQA1-DQB1单倍型特点。方法应用聚合酶链反应-直接测序分型法（PCR-sequence-based typing ，PCR-SBT）方法对100名健康、无血缘关系的江苏汉族人群的HLA-DQA1和DQB1进行基因分型。结果共检出7个DQA1等位基因和13个DQB1等位基因。DQA1等位基因中，DQA1＊0301／02／03的基因频率最高（29．5％），其次为DQA1＊0501（18．5％）、DQA1＊0102（17．0％）、DQA1＊0201（12．5％）；DQB1等位基因中，DQB1＊0201／02（21．5％）、DQB1＊0301／09（14．5％）、DQB1＊0303（13．5％）和DQB1＊0603（11．5％）最为常见。分析得出30种DQA1-DQB1单倍型，DQA1＊0301／02／03-DQB1＊0303（12．5％）、DQA1＊0201．DOB1＊0201／02（10．5％）、DQA1＊0501-DQB1＊0201／02（9．5％）、DQA1＊0501-DQB1＊0301／09（7．0％）为常见的单倍型。结论江苏汉族人群HLA-DQA1和DQB1基因具有较为丰富的多态性，基因频率分布具有中国北方群体的特征且具有一定的独特性。     

西双版纳傣族及上海汉族群体HLA－DR2相关的DR／DQ单倍型分析

对４４名西双版纳傣族和９名上海地区汉族ＤＫ２阳性个体进行了与其相关的ＤＲ／ＤＱ单倍型组合的分析。傣族群体中ＤＲＢＩ－ＤＲ２亚型分布以＊１６０２与＊１５０２为最常见，其等位基因频率分别为４３．６％与，４０．０％和汉族群体中以＊１５０１为主明显不同。傣族群体中共检出１０种与ＤＲ２相关联的ＤＲ／ＤＱ单倍型；最常见的是ＤＲＢ１＊１６０２、ＤＲＢ５＊０１０１、ＤＱＡ１＊０１０２、ＤＱＢ１＊０５０２（３４．５％）与汉族及其他群体明显不同，本研究表明傣族不仅具有高频率的ＤＲ２，而且与ＤＲ２相关联的ＤＲＢ１、ＤＲＢ５、ＤＱＡ１、ＤＱＢ１单倍型组合有其独特性。     

Human leukocyte antigen class II allele frequencies and haplotype association in Iranian normal population.

The polymorphism of the HLA class II genes DRB1, DQA1, and DQB1 was investigated in 100 unrelated Iranian individuals from Fars province in Southern Iran, using the restriction fragment length polymorphism (RFLP) method. Subtyping of DRB1*04, *15, and *16 alleles was performed using PCR amplification with sequence specific primes (PCR-SSP). The allele and the haplotype frequencies were calculated. The most common DRB1 alleles were DRB1*11, DRB1*15, and DRB1*04 with a frequency of 25.0%, 14.5%, and 10.5%, respectively. In contrast, the allelic frequency of DRB1*12 and DRB1*08 was very low (1.5% for each). In the DR15 group DRB1*1501 was the most prevalent variant (6.0%). Concerning DR4, the most common alleles were DRB1*0405 and DRB1*0402 (3.5% for each). Interestingly, DRB1*0402 was associated with DQB1*0302 and DRB1*0405 was associated with DQB1*0302 and DQB1*02, the latter being a rare DRB1/DQB1 haplotype in Caucasian individuals. The most frequent DQB1 alleles were DQB1*0301 (31.0%), and DQB1*05 (22.0%). The most frequent DQA1 variants were DQA1*0501 (39.0%) and DQA1*0102 (14.5%). The most common haplotype was DRB1*11-DQB1*0301-DQA1*0501 (25.0%) followed by DRB1*0301-DQB1*02-DQA1*0501 (10%) and DRB1*0701- DQB1*02-DQA1*0201 (6.5%). Data presented in this study suggest that the Iranian population shares some HLA components with populations resident in eastern and southern European countries.     

HLA-DRB1, DQA1, DQB1 DNA polymorphism in the Bulgarian population

We describe for the first time the use of PCR based techniques to analyze the MHC class II polymorphism of the Bulgarian population. The present study provides the HLA-DRB, DQB1 allele frequencies in 116 Bulgarian individuals and DQA1 alleles frequencies in 100 subjects. DNA from these individuals was typed for DRB and DQB1 typed by the PCR- Allele Specific Amplification (PCR-ASA) method and DQA1 by PCR followed by hybridization using Sequence Specific Oligonucleotides (PCR-SSO). Allele and haplo-type frequencies and linkage disequilibria are computed by the standard methods used for the XIth International Histocompatibility Workshop. The highest frequencies are 0.159, 0.109 and 0.085 for DRB1*1101, DRB1*1601 and DRB1*1301 respectively. Among the eight DQA1 alleles detected, DQA1*0501 (0.344) is found to be much more frequent than the two most frequent alleles DQA1*0102 (0.225) and DQA1*0101 (0.151). Twelve DQB1 alleles are found and three of them, DQB1*0301 (0.280), DQB1*0502 (0.153) and DQB1*0201 (0.133) showed the highest frequencies. The haplo-type DRB1*1101-DQA1*0501-DQB1*0301 (0.079) predominate clearly, followed by DRB1*1601-DQA1*0102-DDQB1*0502 (0.055) and DRB1*0101-DQA1*0101-DQB1*0501. These results indicate that the Bulgarian population is characterized by features representative of the European anthropological type with a substantial contribution from the Southern Belt of Europe.     

Novel HLA-DR2 and -DR3 haplotypes among Norwegian Caucasians

In the Northern European population, all DR2 haplotypes encoded by DRB1*1501 have previously been found to carry the DQA1*0102 and DQB1*0602 alleles, and DR3 haplotypes have been found to carry the DQA1*0501 and DQB1*0201 alleles. Here we report a novel recombinant DR2 haplotype carrying the DRB1*1501, DQA1*0102 and DQB1*0603 alleles as well as a novel recombinant DR3 haplotype carrying the DRB1*0301, DRB3*0101, DQA1*0102 and DQB1*0602 alleles.     

HLA—DR,DQ基因多态性与系统性红斑狼疮相关性的研究

应用聚合酶链反应结合顺序特异的寡核苷酸探针杂交（ＰＣＲ／ＳＳＯＰＨ）方法对江苏籍汉族ＳＬＥ患者和健康对照组ＨＬＡ－ＤＲＢ１、ＤＱＡ１：ＤＱＢ１基因作寡核苷酸分型。结果发现患者组中ＤＲＢ１＊１５０１、ＤＱＡ１＊０１０２等位基因频率及ＨＬＡ－ＤＲＢ１＊１５０１、－ＤＱＡ１＊０１０２、－ＤＱＢ１＊０６０２单倍型频率均明显高于正常对照组；相反，ＤＲＢ１＊０４（ＤＲ４）、ＤＱＡ１＊０６０１频率则明显低于正常对照组。所有ＤＱＢ１等位基因频率在两组间无显著差异，而ＤＱＡ１＊０１０２仅存在于ＤＲ２阳性的个体之中，推测汉族ＳＬＥ的易感基因可能靠近ＤＲ位点，且与单倍型ＨＬＡ－ＤＲＢ１＊１５０１、－ＤＱＡ１＊０１０２、－ＤＱＢ１＊０６０２紧密连锁，该单倍型可作为汉族ＳＬＥ易感的遗传标记。相反ＤＲ４，ＤＱＡ１＊０６０１则对ＳＬＥ发病可能有一定的保护性。     

A study of Italian pediatric celiac disease patients confirms that the primary HLA association is to the DQ(alpha 1*0501, beta 1*0201) heterodimer.

Celiac disease (CD) has been recently reported to be primarily associated with the DQ(alpha 1*0501, beta 1*0201) heterodimer encoded in cis on DR3 haplotype and in trans in DR5,7 heterozygous individuals. The high incidence of DR5,7 heterozygotes, reflecting the high frequency of the DR5 allele in Italy, makes the analysis of the Italian CD patients critical. Polymerase chain reaction-amplified DNA from 50 CD patients and 50 controls, serologically typed for DR and DQw antigens, was hybridized with five DQA1-specific oligonucleotide probes detecting DQA1*0101 + 0102 + 0103, DQA1*0201, DQA1*0301 + 0302, DQA1*0401 + 0501 + 0601, and DQA1*0501 and a DQB1-sequence-specific oligonucleotide probe recognizing DQB1*0201 allele. As expected by the DR-DQ disequilibria, DQA1*0201 [62% in patients versus 26% in controls, relative risk (RR) = 5] and DQA1*0501 (96% versus 56%, RR = 19) show positive association with the disease. Of CD patients, 92% (50% DR3 and 42% DR5,7) compared to 18% of the controls carry both DQA1*0501 and DQB1*0201 alleles, so that the combination confers an RR of 52, higher than both the risks of the single alleles (DQA1*0501 RR = 19, DQB1*0201 RR = 30), confirming the primary role of the dimer in determining genetic predisposition to CD both in DR3 and in DR5,7 subjects.