先兆子痫患者HLA-DQA1、-DQB1、-DPA1基因多态性

目的:探讨人类白细胞抗原HLA-DQ-A1、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(PCRSSP)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HLADQA1基因表型、16种HLADQB1基因表型、6种HLADPA1基因表型。先兆子痫患者HLA-DQ-B10301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:HLADQB10301基因可能是一种先兆子痫发病的易感基因。     

成都地区妊娠期肝内胆汁淤积症与人类白细胞抗原-DQA1的相关性研究

目的探讨妊娠期肝内胆汁淤积症（intrahepatic cholestasis of pregnancy, ICP）与人类白细胞抗原-DQA1（human leukocyte antigen-DQA1, HLA-DQA1）位点等位基因多态性的关系。方法采用聚合酶链反应-序列特异性引物法（polymerase chain reaction with sequence-specific primer, PCR-SSP）对成都地区45例ICP孕妇、18个ICP家庭、45名正常妊娠孕妇及18个正常对照家庭进行HLA-DQA1等位基因分型分析。结果ICP组孕妇HLA-DQA1＊0301等位基因频率明显低于正常对照组孕妇，除此之外，HLA-DQA1其余各等位基因的基因频率在正常对照组和ICP组之间差异无统计学意义。两组夫妇及母胎HLA-DQA1等位基因共享比较亦无统计学意义。结论成都地区人群中HLA-DQA1各等位基因与ICP的发生无明显相关性；HLA-DQA1＊0301等位基因可能是ICP的遗传保护基因，对疾病的发生可能有拮抗作用。     

云南彝族2型糖尿病与HLA-DQA1等位基因多态性的关联研究

目的探讨云南彝族2型糖尿病与HLA—DQA1等位基因多态性的关联性。方法采用聚合酶链反应-序列特异性引物技术，对58例云南楚雄地区彝族2型糖尿病患者和同地区82名彝族正常对照者进行基因分型，做2型糖尿病与HLA—DQA1等位基因多态性的关联分析。结果云南彝族2型糖尿病组与彝族对照组比较，HLA-DQA1＊0301等位基因频率明显高于对照组（P=0．002，RR=3．097）；HLA—DQA1＊0601等位基因频率明显低于对照组（P=0．025，RR=0．429），差异有统计学意义。结论HLA—DQA1＊0301是云南彝族2型糖尿病的易感基因；HLA—OQAI＊0601是云南彝族2型糖尿病的保护基因。     

组合分析法探讨HLA-DRB1、-DQA1等位基因与乙型肝炎病毒感染结局的关系

目的采用组合分析法探讨中国北方汉族人群HIA．DRB1、-DQA1等位基因与乙型肝炎病毒（hepatitisBvirus，HBV）感染不同结局的关系。方法采用序列特异性引物多聚酶链式反应（PCR-SSP）技术对207名慢性乙型肝炎患者和148名自限性HBV感染者进行HLA-DRB1、-DQA1等位基因的检测，并运用病例对照研究设计和组合分析法比较HLA-DRB1、-DQA1等位基因与HBV感染不同结局的关系。结果携带HIA-DQA1＊0102或HLA-DQA1＊0301等位基因者，感染HBV后发展为慢性乙肝的风险显著低于不携带这些等位基因者，比值比（oddsratio，OR）分别为0．23和0．52。用此两个等位基因进行组合分析发现，仅携带HLA-DQA1＊0102或HLA-DQA1＊0301任何一个等位基因者，较不携带HLA-DQA1＊0102和HLA-DQA1＊0301两个等位基因者发展为慢性乙肝的风险显著降低（OR=0．28，X^2=31．16，P〈0．0031），而同时携带HLA-DQA1＊0102和HLA-DQA1＊0301两等位基因者，发展为慢性乙肝的风险降低则更为明显（OR=0．16，X^2=5．86，P=0．02）。结论具有两个保护（或危险）作用的等位基因者比不具有或仅有其中一个等位基因者对HBV感染的结局影响更大。     

动脉粥样硬化性血栓性脑梗死与HLA-DQA1肽结合基序的相关性研究

目的：针对动脉粥样硬化性血栓性脑梗死（atherothrombotic brain infarction,ABI)多基因致病特点,探讨ABI患者的分子免疫遗传学背景。方法：采用聚合酶链反应－序列特异性引物技术检测了81例ABI患者及99名正常对照的HLA－DQA1位点的等位基因频率。结果：（1）HLA－DQA1＊0301等位基因频率明显升高（χ^2=10.9610,P＜0．001）,差异有显著性;（2）有高血压家族史的ABI患者较无高血压家族史的ABI患者HLA－DQA1＊0301等位基因明显升高（χ^2=6.7472,P＜0．01),差异有显著性;（3）ABI患者的HLA－DQA1＊0103等位基因频率较正常对照明显降低（χ^2=5.6313,P＜0．05）,差异有显著性。结论：HLA－DQA1＊0301等位基因与ABI的发病有一定的关系,与有原发性高血压阳性家庭史的ABI的发病可能有关,而HLA－DQA1＊0103等位基因可能是ABI的保护性基因。     

先兆子痫患者外周血、脐血及蜕膜NK细胞的相关研究

目的：对先兆子痫孕妇外周血、脐血及蜕膜NK细胞进行研究，以探讨先兆子痫的病因。方法：对42例先兆子痫患者及20例正常孕妇外周血、脐血NK细胞分离后记数。采用免疫组织化学法检测胎盘蜕膜NK表型后记数并检测其平均灰度。结果：①轻度及重度先兆子痫患者母血及脐血NK细胞数均显著高于正常孕妇（P〈0．05）；②重度先兆子痫患者蜕膜NK细胞数高于正常孕妇（P〈0．05）；③轻度及重度先兆子痫患者胎盘蜕膜NK细胞CD56组化染色平均灰度值高于正常孕妇（P〈0．05）。结论：先兆子痫患者外周血、脐血及蜕膜的NK细胞数量均高于正常孕妇，且呈激活状态的胎盘蜕膜NK细胞较多，可能与发病有关。     

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。     

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基因与子痫前期相关性研究

目的探讨HLA-DRB1基因与子痫前期相关性。方法采用序列特异性引物技术（PCR—SSP）对119例子痫前期患者、117例正常孕妇及其新生儿进行HLA-DRB1等位基因分型，比较其基因频率。结果共检出13种等位基因，两组孕母或两组新生儿间，其HLA-DRB1等位基因频率差异无统计学意义（Pc〉0．05）；子痫前期组和正常晚孕组母婴所携带HLA-DRB1＊014、-DRB1＊10、-DRB1＊14等位基因配伍差异有统计学意义（P〈0．05）。结论母婴所携带某些HLA-DRB1基因配伍与子痫前期易感性或抗性相关；父源性HLA-DRB1＊014基因与子痫前期易感性相关。     

AITDs与HLA等位基因DQA1*0301、DR9的相关性研究

目的：探讨山东沿海地区自身免疫性甲状腺病（AITDs)与HLA－DQA1＊301，DR9的相关性。方法：采用多聚酶链式反应序列特异物分析（PCR－SSP）技术，扩增HLA等位基因DQA1＊0301，DR9的目的DNA片段（分别为199，236 bP)，分析2对等位基因在不同人群中表面频率的差异（χ^2检验），结果：山东沿海地区GD和HT女性患者组DQA1＊0301等位基因频率均显著高于对照组（分别为P＜0．001，OR＝4．89，P＜0．01，OR＝4．95）；DR9等位基因频率仅HT女性组显著高于对照女性组（P＜0．05，OR＝3．90），DQA1＊0301／DR9共同表达的频率，GD和HT女性组较对照女性组均显著性增高（分别为P＜0．05，P＜0．01），GD组和HT组2组间均无显著性差异（P＞0．05），结论：HLA－DQA1＊0301等位基因是山东沿海地区女性GD患者的易感基因；DQA1＊0301，DR9等位基因均是该地区女性HT患者的易感基因，2对等位基因在男性AITDs患者中的分布情况尚待进一步观察。     

New DRB1* alleles (HLA-DRB1*1135, DRB1*1430 and DRB1*1433) and a confirmatory sequence (DRB1*1133)

Three new DRB1 alleles (DRB1*1135, DRB1*1430 and DRB1*1433) and a confirmatory sequence (DRB1*1133) have been identified after following up unusual or novel polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) patterns during routine typing of the DRB1*03,*08,*11,*12,*13 and *14 allele groups. Of the new alleles found and described in this paper, two alleles were initially detected by the PCR-RFLP method which produced unexpected restriction polymorphism (DRB1*1133 and DRB1*1135) while the remaining two were found after following up rare allele typings from this technique (DRB1*1430 and DRB1*1433).     

HLA-Cw*1701 is associated with two sub-Saharan African-derived HLA haplotypes: HLA-B*4201, DRB1*03 and HLA-B*4202 without DRB1*03

Different extended haplotypes have been described for many ethnic groups, such as African-Americans. The complotype FC(1,90)0 is in linkage disequilibrium with HLA-B42, DRB1*0302 in African-Americans and Southern African Xhosa individuals, suggesting a common ancestry. In order to analyze the distribution of Cw*17 alleles (Cw*1701, 1702) in relation to this African-derived extended haplotype, we studied a large panel of samples from African-American individuals and additionally a group of selected samples carrying HLA-B42, DR3 and HLA-B42, non-DR3 antigens. HLA alleles were assigned using sequence-specific amplification (SSP) and sequence-specific oligonucleotide probe hybridization (SSOP). We have found that all haplotypes (10 in total) carrying the extended haplotypes [HLA-B42, FC(1,90)0, DRB1*0302] were positive for HLA-Cw*1701. Interestingly, HLA B*4201 was found in all samples (17 in total) carrying HLA-B42, DR3, Cw*1701, whereas HLA-B*4202 was found in 10 out of 13 samples from individuals carrying HLA B42, Cw*1701 non-DR3. These findings suggest that HLA-Cw*17 polymorphism is conserved in different ethnic populations and that HLA-B42 alleles seem to separate at least different African-derived haplotypes. The historical context of these findings are important for the study of human evolution and they may be useful for the development of strategies in the search for possible donors in organ transplantation for African-derived populations.     

Association of HLA-DRB1 genetic variants with the persistence of atopic dermatitis

Atopic dermatitis (AD) is a waxing and waning illness of childhood that is likely caused by interactions between an altered skin barrier and immune dysregulation. The goal of our study was to evaluate the association of DRB1 genetic variants and the persistence of AD using whole exome sequencing and high resolution typing. DRB1 was interrogated based on previous reports that utilized high throughput techniques. We evaluated an ongoing nation-wide long-term cohort of children with AD in which patients are asked every 6 months about their medication use and their AD symptoms. In total, 87 African-American and 50 European-American children were evaluated. Genetic association analysis was performed using a software tool focusing on amino acid variable positions shared by HLA-DRB1 alleles covering the antigen presenting domain. Amino acid variations at position 9 (pocket 9), position 26, and position 78 (pocket 4) were marginally associated with the prevalence of AD. However, the odds ratio was 0.30 (0.14, 0.68; p = 0.003) for residue 78, 0.27 (0.10, 0.69; p = 0.006) for residue 26 and not significant for residue 9 with respect to the persistence of AD. In conclusion, amino acid variations at peptide-binding pockets of HLA-DRB1 were associated with the persistence of AD in African-American children.     

Three new DRB alleles routinely identified by sequence-based typing: DRB1*010103, DRB1*0326 and DRB3*0219

We describe here two additional DRB1 alleles found in two Caucasoid recipient candidates for organ transplant and a new DRB3 allele found in a Caucasoid unrelated bone marrow donor from the German file. HLA-DRB generic and allele typing were performed using commercial kits, subsequently exon 2 was sequenced. We found a DRB1*010101 with a silent mutation at codon 68 and a DRB1*0306 with a mutation at codon 38 (T-C) which causes an amino acid substitution from Val to Ala. DRB3*0219 differs from DRB3*020201 by two-point mutations at codons 60 and 74 (A/C and A/G, respectively). These mutations at positions 266 and 308 were responsible for two amino acid substitutions (Tyr to Ser and Gln to Arg).     

Distribution of HLA-DRB1, DPB1 and DQB1 alleles and haplotypes in Mongolian Minority in China

HLA-DRB1, -DQB1 and -DPB1 allele frequencies and estimated haplotype frequencies from 496 unrelated healthy Mongol subjects who living in Inner Mongolia Autonomous Region of China has been reported. HLA genes were genotyped using high-resolution sequence-based typing method. Chinese-Mongolian belongs to northern group of East Asians, but with its specific HLA-DRB1, DPB1 and DQB1 alleles and haplotypes characteristic.     

HLA-A, -B, -C, -DQA1, -DQB1, -DRB1, -E, -F and -G genotyping of 130 individuals from Terceira Island,Azores, Portugal

One hundred and thirty unrelated Azorean individuals were randomly selected to study the frequencies of high-resolution HLA alleles and haplotypes in the Azorean (Terceira) population. HLA-A, -B, -Cw, -DRB1, -DQA1 and -DQB1 high-resolution genotyping was performed by polymerase chain reaction using commercial kits. HLA-E, -F and -G alleles, were genotyped by sequence-based typing. All loci were in HWE, showing no locus-level deviations. The genotype data is available in the Allele Frequencies Net Database under the population name “Azores Terceira Island” and the identifier (AFND112579).     

Human leukocyte antigen class I (A,B, C) and class II (DPB1, DQB1, DRB1) allele and haplotype variation in Black South African individuals

South Africa has a population of 58.78 million, of which 80.7% are Black African individuals, representing 9 predominant ethnic/linguistic groups (Zulu, Xhosa, Pedi, Tswana, South Sotho, Tsonga, Swati, Venda and Ndebele). HIV-1 and Mycobacterium tuberculosis infection are the leading causes of death (7.8% and 5.9%, respectively) in this population group. To provide reference HLA allele and haplotype data for studies of gene-associations with infectious/non-infectious diseases or vaccine development, we have updated previously published HLA class I (A, B, C) and class II DRB1 genotypes and determined high-resolution class II (DPB1, DQB1) genotypes for n = 142 healthy, unrelated Black South African individuals.