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。     

HLA-DRB1和HLA—DQB1基因与肿瘤的关联性研究

目的通过对42例肿瘤患者HLA-DRBl和HLA—DQB1座位的18个等位基因位点的检测,探讨HLA—DRB1和HLA—DQB1基因多态性与肿瘤的关联性。方法采用PCR—SSP技术,检测42例肿瘤患者的HLA—DRB1l和HLA—DQB1基因位点18个,并以100例健康人作为对照。结果肿瘤HLA—DQB1＊03型频率的65．5％,高于对照组的42．0％,RR=2．62,P〈0．0001;肿瘤组HLA—DQB1％06型频率为10．7％,明显低于对照组的24．0％,RR=0．38,P=0．010。结论HLA-DQB1＊03可能是肿瘤的易感基因,HLA-DQB1＊06可能是肿瘤的抗性基因。     

山东沿海地区碘营养状况和HLA等位基因DQA1*0501、DQA1*0201对AITDs发病的影响

目的探讨山东沿海地区自身免疫性甲状腺病（AITDs）与HLA等位基因DQA1＊0501、DQA1＊0201及碘营养状况对AITDs发病的影响。方法HLA等位基因测定采用PCR-SSP技术,尿碘浓度测定采用砷铈催化分光光度法。结果①DQA1＊0501等位基因为AITDs易感基因（GD和HT的OR值=2．14、2．5）;而DQA1＊0201为女性AITDs保护基因（GD和HT的OR值=0．33、0．27）。②AITDs组尿碘浓度高于300μg／L患者分布频率均显著高于对照组（P〈0．05）,且DQA1＊0501（＋）发生AITDs的OR值为2．7,DQA1＊0201（＋）的OR值为0．42;AITDs组碘正常组DQA1＊0501（＋）OR值为5．12,DQA1＊0201（＋）的OR值为0．21。③logistic回归分析发现尿碘浓度对数、DQA1＊0501为AITDs的易感因素,DQA1＊0201为保护因素。结论HLA-DQA1＊0501等位基因与该地区AITDs的发病易感性相关,而DQA1＊0201与女性患者的保护性相关。碘和HLA等位基因DQA1＊0501、DQA1＊0201共同影响GD、HT的发病。     

用核酸序列测定1型糖尿病HLA-DPB1和DQB1第2外显子基因

目的 研究山东省汉族1型糖尿病与HLA－DPB1和HLA－DQB1等位基因的相关性。方法 采用基于核酸序列测定的基因分型技术对52例1型糖尿病患者及38例正常对照进行了DPB1和DQB1基因分析。结果 DPB1＊2201（P＜0．01）和DQB1＊0201（P＜0．01）、＊0303（P＜0．05）及＊0604（P＜0．05）等位基因频率在糖尿病患者组显著高于对照组,而PB1＊0402（P＜0．01）和DQB1＊0301（P＜0．01）等位基因在糖尿病患者组显著低于对照组。结论 DPB1＊2201和DQB1＊0201、＊0303及＊0604等位基因可能是山东省汉族1型糖尿病的易感性等位基因,而DPB1＊0402和DQB1＊0301等位基因可能是山东省汉族1型糖尿病的保护性等位基因。     

先兆子痫患者HLA-DQA1、-DQB、-DPA1基因多态性

目的：探讨人类白细胞抗原HLA-DQA1、-DQB1、-DPA1基因多态性与先兆子痫发病的关系。方法：采用序列特异性引物技术（PCR-SSP） 对46例先兆子痫患者和105例正常孕妇及其新生儿进行HLA-DQ-DPA1等位基因分型。结果：所有标本共检出11种HLA-DQA1基因表型、16种HLA-DQB1基因表型、6种HLA-DPA1基因表型。先兆子痫患者HLA-DQB1＊0301基因频率高于正常孕妇，差异有显著性（Pc=0．032，RR=2．43，AR=0．30），其余各基因表型频率两组比较差异均无显著性。结论：HLA-DQB1＊0301基因可能是一种先兆子痫发病的易感基因。     

广东汉族人十二指肠溃疡和HLA-DQB1等位基因的关联研究

目的探讨广东地区汉族人人类白细胞抗原-DQB1（human leukocyte antigen-DQB1，HLA-DQB1）等位基因与十二指肠溃疡（duodenal ulcer，DU）的遗传关联。方法应用聚合酶链反应．序列特异性引物核苷酸分型技术，对105例DU患者、105名正常人的HLA-DQB1等位基因进行分析。结果DU患者HLA-DQB1 ＊0602等位基因频率与正常对照组比较明显增高，差异有统计学意义（P=0．001，RR=4．533，Pc：0．014）。结论HLA-DQB1＊0602与十二指肠溃疡有一定关联，HLA-DQB1等位基因分布在十二指肠溃疡患者与正常人之间存在着差异。     

华南、华北人群HLA-DQB1等位基因多态性

目的从基因水平调查了中国华南、华北地区人群HLA-DQB1等位基因频率，并研究比较两地区人群HLA-DQB1多态性分布。方法采用深圳益生堂生物企业有限公司研制开发的“HLA-DQB1低分辨率分型基因芯片检测试剂盒”，应用聚合酶链反应．序列特异性引物＋序列特异性寡核苷酸探针芯片检测技术，对700名南方地区的中国人和320名北方地区的中国人进行基因分型。结果鉴定了10个HLA-DQB1等位基因，获得了一组准确、科学的统计数据。结论得到了中国华南、华北地区人群HLA-DQB1等位基因频率差异的数据，证明中国人群HLA-DQB1＊02，05，0601，0602，0603的分布南北差异有统计学意义（P〈0．05），为疾病相关性研究、人文科学研究提供了可靠的遗传学数据。     

山西省家族性乙型肝炎病例中HLA-DRB1基因位点的分析

目的 探讨HLA-DRB1等位基因多态性与家族性乙型肝炎之间的关系.方法 采用聚合酶链反应-特异性序列寡核苷酸（PCR-SSO）探针基因分型技术结合荧光磁珠流式检测仪,对151例家族性乙肝人群的HLA-DRB1基因位点进行了分析.结果 HLA-DRB1＊0701在慢乙肝组的等位基因频率（17.8%）明显高于正常对照组（7.4%）,差异有统计学意义（P＜0.05,A=1/0.367=2.725）;HLA-DRB1＊0401/0403/0405及HLA-DRB1＊1301/1302在正常对照组的等位基因频率（16.2%;4.4%）明显高于慢乙肝组（5.1%;0）,差异有统计学意义（P＜0.05,A=3.602;P＜0.05）.结论 HLA-DRB1＊0701与家族性慢性乙型肝炎易感性相关,可能是家族性慢性乙型肝炎的易感基因或连锁基因;HLA-DRB1＊0401/0403/0405、HLA-DRB1＊1301/1302与家族性慢性乙型肝炎抗性相关,可能是家族性慢性乙型肝炎的抗性基因.宿主的HLA-DRB1可能是预测家族性乙肝转归的主要指标.     

HLA Ⅰ、Ⅱ类基因多态性与白塞病的相关性研究

目的 探讨HLAⅠ、Ⅱ类基因在白塞病（BD）易感性中的作用。方法 应用LABType^TM SSO技术（又称序列微珠综合分析实验系统）对40例BD患者及100例正常对照的HLAⅠ、Ⅱ类基因进行检测。结果 与正常对照组相比，BD患HLA＊51（30％vs12％，X^2=5．312，OR=3．143，P〈0．05）、HLA-DRB1＊14（22．5％vs8％，X^2=4．354，OR=3．339，P〈0．05）的频率显著增高，HLA-DRB1＊15（10％vs30％，X^2=5．175，OR=0．259，P〈0．05）的频率显著降低。结论 本研究结果提示HLA-B＊51、HLA-DRB1＊14可能是BD的易感基因，HLA-DRB1＊15可能是BD的保护性基因。     

CD14启动子-159位点基因多态性与冠状动脉粥样硬化性心脏病的相关性研究

目的研究湖北地区汉族人群CD14启动予-159（C→T）多态性分布，探讨该多态性与冠状动脉粥样硬化性心脏病（冠心病）的相关性。方法应用聚合酶链反应-限制性片段长度多态性技术对湖北地区汉族162例冠心病患者及196名正常对照组者CD14基因启动子-159位点进行基因型分析。结果CD14启动子-159位点基因型频率和等位基因频率在冠心病组和对照组间比较差异有统计学意义，（基因型：X^2=0．654，P〈0．05，CT vs CC，OR=1．245，95％CI：1．001～1．473，TT vs CC，OR=2．374，95％CI：2．012～2．649；等位基因：X^2=0．547，P〈0．05，TvsC，X^2=0、547，P〈0、05，OR=3．105，95 ％CI：2．493～3．539）：CD14启动子-159位点基因型频率和等位基因频率在非心肌梗塞组和心肌梗塞组间比较差异有统计学意义（基因型：X^2=0．782，P〈0．05，CF vs CC，OR=2．375，95％CI：2．017～2．689，TT vs CC．OR=3．459，95％CI：3．003～3．846；等位基因：X^2=2．374，P〈0．05，T vs C，X^2=2．374，P〈0．05，OR=4．011，95％CI：3．814～4．279），然而，我们没有发现往冠心病狭窄血管支数之间存存差异。结论CD14启动子-159（C→T）基因多态性中的T等位基因可能是心肌梗塞的遗传学风险因素。     

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，     

Associations of HLA class II alleles with pulmonary tuberculosis in Thais.

Tuberculosis is an important infectious disease in Thailand. Susceptibility to tuberculosis is influenced not only by the environment but also by host genetic factors. In this study, we investigated HLA alleles in 82 patients with tuberculosis from Bangkok and in 160 normal controls. HLA-DRB1, DQA1 and DQB1 genotyping was performed by the PCR-SSO method. The frequency of HLA-DQB1*0502 was increased in tuberculosis patients compared to the normal controls (P = 0.01, OR = 2.06). In contrast, the frequencies of DQA1*0601 and DQB1*0301 were decreased in tuberculosis patients compared to the controls (P = 0.02 and P = 0.01, respectively). Our results suggest that HLA-DQB1*0502 may be involved in the development of pulmonary tuberculosis, whereas HLA-DQA1*0601 and DQB1*0301 may be associated with protection against tuberculosis.     

山西汉族原发性干燥综合征与HLA-DQ基因多态性相关性的研究

目的:探讨山西汉族人群原发性干燥综合征(pSS)与HLA-DQ等位基因的相关性,从基因水平上探索pSS的发病机制。方法:应用聚合酶链反应-序列特异性引物(PCR-SSP)法对pSS患者与健康对照进行HLA-DQA1、HLA-DQB1基因的分型;采用χ2检验和Fisher’s精确检验比较两组各等位基因频率的差异。结果:(1)在100例山西汉族健康人及pSS患者中,HLA-DQA1*0501基因频率分别为12.0%和22.0%。与健康对照相比较,pSS患者中HLA-DQA1*0501基因频率显著增高(χ2=7.087,P<0.05,RR=2.068)。(2)pSS患者HLA-DQA1*0301/2等位基因频率为13.0%,显著低于健康对照组的24.5%(χ2=8.681,P<0.05,RR=0.460)。(3)pSS患者中HLA-DQB1*0201基因频率为28.5%,显著高于健康人的18.5%(χ2=5.563,P<0.05,RR=1.756)。结论:HLA-DQA1*0501和HLA-DQB1*0201等位基因可能是山西汉族pSS的易感基因,而HLA-DQA1*0301/2等位基因可能是其保护基因。     

Myasthenia gravis patients with thymus hyperplasia and myasthenia gravis patients with thymoma display different HLA associations

Thirty myasthenia gravis (MG) patients (9 with thymoma, 12 with thymus hyperplasia and 9 with thymic atrophy) and 181 Norwegian healthy controls were serologically typed for HLA-A, -B and -DR antigens and genomically typed for HLA-DQA1 and HLA-DQB1 alleles by probing in vitro amplified DNA with sequence-specific oligonucleotides. In patients with thymus hyperplasia the frequency of the DQB1*0201 allele was increased compared to controls (RR = 3.5, p less than 0.05), whereas among the patients with thymoma this allele was not observed (RR = 0.06, p less than 0.01). The frequencies of HLA-B8, -DR3 and -DQA1*0501, which are in strong linkage disequilibrium with DQB1*0201, were increased in patients with hyperplasia and reduced in patients with thymoma. The data suggest that different HLA genes predispose to two different forms of MG.     

A variant of childhood-onset myasthenia gravis: HLA typing and clinical characteristics in Japan

To investigate the correlation between clinical features and HLA DR/DQ genetic variability in myasthenia gravis (MG), we evaluated HLA DR/DQ allele frequencies in 87 Japanese patients with childhood-onset disease. HLA genotypes DRB1*1302/DQA1*0102/DQB1*0604 and DRB1*0901/DQA1*0301/DQB1*0303 were significantly higher in patients than in healthy controls (P(c) < 0.0001, RR = 5.5; P(c) < 0.0001, RR = 8.5, for two genotypes, respectively). Patients who had a significantly higher likelihood of the HLA types DRB1*1302/DQA1*0102/DQB1*0604 or DRB1*0901/DQA1*0301/DQB1*0303 belonged to the latent general type (LG) of MG; this is clinically ocular type, but shows myasthenic electromyographic findings in extremity muscles. The LG type of MG was observed in 78% of patients exhibiting the clinically ocular type; this group comprised approximately 75% of patients with childhood-onset MG. These date suggest that LG type of MG may present a particular subset of childhood-onset MG, which is associated with the specific HLA subtypes DRB1*1302/DQA1*0102/DQB1*0604 and DRB1*0901/DQA1*0301/DQB1*0303.     

HLA-DQA1、DQB1、DRB1 02,07,09等位基因及单倍型在华东地区汉族人群的分布

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（０．３８４４），其次为＊０５０１（０．１４０６）和０１０２（０．１２１９），＊０４０１最低（０．０２８１）；ＤＱＢ１中以ＤＱＢ１＊０３０３基因频率最高（０．２３４２），其次为＊０３０１（０．１８９９）、＊０６０１（０．１２０３）和＊０２０１（０．１１０８），＊０５０１、＊０６０４和＊０６０５最低（均为０．０１２７）；ＤＲ９基因频率较高（０．２３１０），ＤＲ２中ＤＲＢ１＊１５０１占７３％，基因频率为０．０８５４，未见＊１６０１。ＤＱＡ１、ＤＱＢ１及ＤＲＢ１等位基因之间存在显著的连锁不平衡。ＤＲＢ１＊０９０１－ＤＱＡ１＊０３０１－ＤＱＢ１＊０３０３、ＤＱＡ１＊０１０３－ＤＱＢ１＊０６０１等为常见单倍型。本资料与我国其他汉族人群资料有可比性，也存在一定差异。     

HLA-DR and -DQ associations with insulin-dependent diabetes mellitus in a population of Turkey

Genetic susceptibility to insulin-dependent diabetes mellitus (IDDM) has been shown to be associated with MHC in many studies. To extend this data with a population with relatively low IDDM incidence, MHC DRB, DQA, and DQB have been investigated by polymerase chain reaction and sequence specific oligonucleotide probe hybridization (PCR/SSO) in 178 IDDM patients from Turkey and compared to 248 healthy controls. Significant differences are detected between IDDM and control groups in the frequencies of DRB1*0402 DQA1*03 DQB1*0302 (28.1% vs. 5.2%, p < 0.0001, OR: 7.1) and DRB1*0301 DQA1*0501 DQB1*02 (57% vs. 18.1%, p < 0.0001, OR: 6.1). Among the negative associations, the most strong ones are with DRB1*1401 DQA1*0101 DQB1*0503 (0.6% vs. 8.9%, p < 0.0001, OR: 0.1), DRB1*1502 DQA1*0103 DQB1*0601 (1.1% vs. 7.7%, p = 0.0023, OR: 0.1), DRB1*1301 DQA1*0103 DQB1*0603 (0.6% vs. 6.9%, p = 0.0039, OR: 0.2) and DRB1*1101 DQA1*0501 DQB1*0301 (3.9% vs. 12.1%, p < 0.0001, OR: 0.2). When the DRB, DQA or DQB genotypes of the susceptible alleles are compared, the most strong susceptibility marker of the disease is found to be DRB1*0301/*04 (31.4% vs. 2.8%, p < 0.0001, OR: 15.8) and among these, heterozygote genotype DRB1*0301/*0401 (4.5% vs. 0, p = 0.0008, OR: 24.8).These results confirm the positive associations with IDDM previously observed in other Caucasian populations and reveal many negative and strong associations which maybe underlining several characteristics that distinguish Turkish diabetics form other Caucasians.     

人白细胞抗原(HLA)-DRB1 *0901、1501和HLA-DQB1 *0301、0602与新疆哈萨克族食管鳞状细胞癌相关性

目的 从基因水平探讨新疆哈萨克族食管鳞状细胞癌HLA-DRB1和DQB1等位基因的遗传易感性,为寻找哈萨克族食管鳞状细胞癌的易感基因提供线索.方法 运用序列特异性引物聚合酶链反应(PCR-SSP)技术,检测新疆哈萨克族食管鳞状细胞癌200例、正常食管黏膜177例HLA-DRB1 *0901、1501和DQB1 *0301、0602等位基因的分布.结果 新疆哈萨克族食管鳞状细胞癌患者HLA-DRB1 *1501、DQB1 *0301和DQB1 *0602基因分布频率(0.455,0.760和0.690)明显高于177例正常食管黏膜上述等位基因分布频率(0.232,0.520,0.554),差异具有统计学意义(OR=2.78,2.93,1.80;P值均<0.05);新疆哈萨克族食管鳞状细胞癌HLA-DRB1 *0901等位基因分布频率(0.105)与哈萨克族正常食管黏膜(0.102)对比,差异无统计学意义(OR=11036,P>0.05);HLA-DQB1 *0602等位基因的分布频率在哈萨克族中低分化鳞状细胞癌组中的分布频率(0.742)高于高分化鳞状细胞癌组(0.597),差异具有统计学意义(P<0.05).结论 HLA-DRB1 *1501、DQB1 *0301和DQB1 *0602可能是哈萨克族食管鳞状细胞癌的易感基因,HLA-DQB1 *0602与哈萨克族食管鳞状细胞癌的分化程度有关.     

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.