北京HIV抗体阳性MSM中HLA—A—B—DRB1基因多态性与病毒载量相关性的初步研究

目的从基因水平了解北京艾滋病病毒（HIV）抗体阳性的男男性行为者人群（MSM）中,人类白细胞抗原（HLA）-A、-B、-DRB1位点的等位基因频率,分析其与HIV感染者自身病毒载量的关系。方法应用聚合酶链反应-序列特异性引物技术（PCR—SSP）,对北京32例HIV阳性MSM进行了HLA—A、-B、-DRB1等位基因分型。结果鉴定了12个HLA—A等位基因,21个HI．A—B等位基因,12个HLA—DRB1等位基因。最常见的等位基因分别为A＊02（26．56％）、B＊40（17．19％）和DRB1＊15（20．31％）。含有A＊02等位基因组者的血浆病毒载量,较不含有此等位基因组者低（P-0．002）,而含有HI,AB＊40和HLA—DRB1＊15等位基因组者的血浆病毒载量,较不含有对应等位基因组者高（HLA—B＊40：P-0．799;HLADRB1＊15：P=0．021）。结论北京HIV阳性MSM人群HLA—A、-B、-DRB1基因多态性较高。HLA—A＊02等位基因在该人群中可能与延缓AIDS疾病进程相关,而HLA—DRB1＊15等位基因可能与加速该人群AIDS疾病进程相关。     

山东地区新生儿脐血HLA-A、HLA-B等位基因多态性研究

目的研究山东地区新生儿脐血人类白细胞抗原（HLA—A、HLA—B）等位基因的分布特征．探讨国人用山东脐血供者进行造血干细胞移植的可能性。方法应用PCR—SS0方法对山东地区5844例无血缘关系的汉族健康新生儿脐血进行HLA—A、HLA—B等位基因分布调查。结果检出20种HLA—A等位基因，频率较高的为A＊02（0．3041）、A＊11（0．1443）、A＊24（0．1434）、A＊30（0．0975）和A＊33（0．0859），较低的为A＊34（0．0006）、A＊25（0．0005）、A＊66（0．0005）、A＊74（0．0004）和A＊36（0．0001）。检出46种HLA—B等位基因．频率较高的为B＊13（0．1348）、B＊51（0．0713）、B＊62（0．0712）、B＊61（0．0676）和B＊60（0．0642），较低的为B＊77（0．0001）．B＊76（0．0002）．B＊47（0．0003），B＊42（0．0003）和B＊72（0．0004）。结论山东新生儿脐血HLAI类基因具有多态性，能代表山东汉族人群HLA的分布特征，反映北方汉族HLA的分布规律；国人（尤其是北方汉族人）在山东脐血库中最容易找到HLAI类等位基因相合的异基因脐血供者。     

HLA-DR基因与中国南方汉族部分人群肺结核易感基因的研究

目的　探讨人类白细胞抗原 (HLA) DR基因与中国南方汉族部分人群肺结核发病的关联性 ,并寻找与肺结核发病可能相关的HLA易感基因。方法　采用病例 对照的研究方法 ,应用聚合酶链反应 序列特异性引物 (PCR SSP)技术对 110例中国南方汉族肺结核患者 (肺结核病例组 )和 10 1例中国南方汉族健康对照者 (健康对照组 )的 2 3个HLA DR等位基因进行分型 ,比较其等位基因频率(GF)并计算其比值比 (OR)。结果　HLA DR基因PCR SSP分型显示 :(1)肺结核病例组中的DR16等位基因的基因频率显著高于健康对照组 ,两组的GF值分别为 12 6 2 %、5 6 0 % ,两者之间差异具有显著性 (χ2 =5 915 ,PC<0 0 5 ,OR值为 2 5 3)。 (2 )肺结核病例组中的DR1、DR13 3等位基因的基因频率分别为 8 0 8%、2 3 5 7% ,显著低于健康对照组的 2 9 2 9%、5 0 2 4 % ,两组比较 ,差异具有显著性 (χ2值分别为 17 84 7和 14 2 5 8,PC 值均 <0 0 1;OR值分别为 0 2 6、0 33)。结论　 (1)DR16等位基因与南方汉族部分人群的肺结核发病可能密切相关 ,或与真正起作用的易感基因连锁。 (2 )中国南方汉族部分人群DR1、DR13 3等位基因的表达对结核分枝杆菌感染者的发病可能具有拮抗作用。     

HLA-DQB1-HLA-DRB1单倍型与中国南方汉族肺结核的相关性分析

目的　探讨HLA DQB1 HLA DRB1单倍型在中国南方汉族肺结核发病机制中的可能作用。方法 采用病例 对照的研究方法 ,应用PCR SSP技术对110例中国南方汉族肺结核患者和 10 1例中国南方汉族健康对照者的 2 0个HLA DRB1和 8个HLA DQB1等位基因进行分型 ,比较两组间DQ2,3(8) DRB1、DQ3(7) DRB1、DQ3(8,9) DRB1、DQ2 ,3(7,9) DRB1、DQ2 DRB1、DQ4 DRB1、DQ5DRB1和DQ6 DRB1单倍型频率 (HF)并计算其相对危险性 (RR)。结果 DQ2 ,3(8) DR14 .1、DQ3(7)DR16单倍型的频率肺结核病例组显著高于对照组 (6 .10vs .0 .5 0、4 .18vs .0 .99) ,其RR分别为 13.4 0和 4 .41;DQ2 DR1、DQ2 DR12、DQ2 DR13.3、DQ3(7) DR1、DQ3(7) DR13.3、DQ3(8,9) DR13.3、DQ2,3(7,9) DR1、DQ2 ,3(7,9) DR13.3、DQ2 ,3(7,9) DR13.4、DQ4 DR4单倍型的频率肺结核病例组显著低于对照组(分别为 1.84vs .5 .6 0、1.37vs .5 .6 0、4 .18vs .11.0 0、2 .30vs .9.89、12 .6 2vs .2 2.2 8、5 .6 1vs .11.5 6、3.70vs .14 .4 0、16 .88vs .2 8.94、5 .13vs .12 .12、2 .30vs.6 .13) ,其RR分别为 0 .31、0 .2 3、0 .34、0 .2 1、0 .4 7、0 .4 4、0 .4 6、0 .38和 0.35。结论 DQ2 ,3(8) DR14 .1、DQ2 DR12、DQ2 ,3(7,9 )-DR13.4、DQ4-DR4单倍型的存在可能与中国南方汉族肺结核的发病有着关联,而其他单倍型差异的显著性则可能是因其组成基因的基因频率差异所致。     

广西巴马县壮族长寿老人HLA-DRB1基因的多态性

目的探讨人类白细胞抗原DRB1(HLA DRB1)基因与长寿的相关性。方法应用聚合酶链式反应序列特异引物(PCR SSP)对广西巴马县109名90岁以上壮族长寿老人(90～103岁)、56名80～89岁和71名当地健康、无血缘关系、生活习性相似、随机抽样的壮族成年人(23～70岁)进行HLA DRB1基因分型及相应等位基因频率的比较。结果在该研究群体中共检出13个HLA DRB1等位基因,最常见的等位基因是HLA DRB11501(长寿组、80岁组和对照组分别为26.61%、26.79%和26.06%),其次是HLA DRB11601/2(以上3组分别为14.22%、14.29%和16.20%)和HLA DRB11401/4(以上3组分别为11.93%、10.71%和11.97%);长寿组HLA DRB11201/2的频率与对照组比较有升高趋势,但无统计学意义;3组间其他相应等位基因频率的比较均无显著差异(P<0.05)。结论在巴马县壮族长寿人群的HLA DRB1座位上,没发现与其长寿明显相关的等位基因。     

陕西地区造血干细胞捐献者人类白细胞抗原HLA等位基因频率分析

目的：了解陕西地区人类白细胞抗原（HLA）-A、B、DRB1等位基因分布的特征。方法：采用PCR-SSP和PCR-SSOP方法对10122名造血干细胞捐献者样本进行HLA-A、B、DRB1等位基因分型分析。结果：鉴定了20个A等位基因,34个B等位基因,14个DRB1等位基因。频率最高的基因型分别为A＊02、B＊15、DRB1＊15,其相应基因频率分别为30.03%、14.09%和15.51%。结论：陕西地区人群HLA-A、B、DRB1等位基因频率具有较丰富的多态性。     

HLA-DQB1-HLA-DRB1单倍型与中国南方汉族肺结核的相关性分析

目的探讨HLA—DQB1．HLA．DRBl单倍型在中国南方汉族肺结核发病机制中的可能作用。方法采用病例．对照的研究方法，应用PCR．SSP技术对110例中国南方汉族肺结核患者和101例中国南方汉族健康对照者的20个HLA．DRBl和8个HLA．DQB1等位基因进行分型，比较两组间DQ2，3(8)-DRB1、DQ3(7)-DRB1、DQ3(8，9)．DRB1、DQ2，3(7，9)．DRB1、DQ2-DRB1、DQ4．DRB1、DQ5-DRB1和DQ6．DRB1单倍型频率(HF)并计算其相对危险性(RR)。结果DQ2，3(8)．DR14．1、DQ3(7)．DR16单倍型的频率肺结核病例组显著高于对照组(6．10vs．0．50、4．18vs．0．99)，其RR分别为13．40和4．41；DQ2-DR1、DQ2-DR12、DQ2．DR13．3、DQ3(7)．DR1、DQ3(7)．DR13．3、DQ3(8．9)-DR13．3、DQ2，3(7，9)-DR1、DQ2，3(7，9)-DR13．3、DQ2，3(7，9)．DR13．4、DQ4-DR4单倍型的频率肺结核病例组显著低于对照组(分别为1．84V8．5．60、1．37V8．5．60、4．18VS．11．00、2．30VS．9．89、12．62V8．22．28、5．61V8．11．56、3．70V8．14．40、16．88V8．28．94、5．13V8．12．12、2．30vs．6．13)，其RR分别为0．31、0．23、0．34、0．21、0．47、0．44、0．46、0．38和0．35。结论DQ2，3(8)．DR14．1、DQ2．DR12、DQ2，3(7，9)-DR13．4、DQ4-DR4单倍型的存在可能与中国南方汉族肺结核的发病有着关联，而其他单倍型差异的显著性则可能是因其组成基因的基因频率差异所致。     

应用PCR-SSOP技术对陕西克山病人HLA-DRB1基因分型的研究

目的 了解陕西克山病人HLA—DRBl基因多态性的特征。方法 应用PCR—SSOP技术对118例克山病人进行HLA—DRBl基因分型。结果 鉴定了克山病人HLA—DRBl位点的10种等位基因，其中高频率分布的有DRl5、DR4、DR9。结论 提供了一套比较完整准确的陕西克山病人DRB1等位基因的基因频率，对群体遗传和疾病关联研究具有参考意义。     

HLA-DRB1、-DQB1基因多态性与食管鳞癌遗传关联性

目的　从基因水平探讨食管鳞癌HLA DRB1 , DQB1等位基因的遗传易感性 ,以阐述其免疫遗传学特征。方法　运用序列特异性引物聚合酶链反应技术 ,检测无亲缘关系湖北汉族健康人 1 36例、食管鳞癌患者 42例的HLA DRB1 , DQB1等位基因。结果　湖北汉族人食管鳞癌患者与正常人比较 ,HLA DRB1 0 90 1等位基因分布频率显著增高 (0 .2 50 0比 0 .1 397,P =0 .0 2 8,OR =2 .0 53 ,病因分数 =0 .1 2 82 ) ,HLA DQB1 0 30 1基因分布频率显著增高 (0 .2 976比 0 .1 875 ,P =0 .0 4 6 ,OR =1 .835 ,病因分数 =0 .1 35 4)。两者间其余HLA DRB1、 DQB1等位基因分布频率差异均无显著性。结论　HLA DRB1 0 90 1及 DQB1 0 30 1等位基因均与食管鳞癌正关联 ,为其易感基因。该两等位基因测序结果与其基因库第 2外显子序列吻合。     

HLA—DRB1、DQB1基因多态性与流行性出血热的相关性

目的从基因水平探讨HLA—DRB1、DQB1等位基因多态性与流行性出血热的相关性,以阐述其免疫遗传学特征。方法应用序列特异性引物聚合酶链反应技术检测流行性出血热患者和正常对照组各50例的HLA—DRB1、DQB1等位基因。结果流行性出血热患者与正常对照组比较,HLA—DRB1＊16等位基因分布频率明显增高（Pc=0．0106）,两组间其余HLA-DRB1、-DQB1等位基因分布频率差异无统计学意义（Pc〉0．05）。结论HLA-DRB1＊16等位基因与流行性出血热呈正相关,可能为流行性出血热易感基因之一。     

Increase of HLA-DRB1*0408 and -DQB1*0301 in HLA-B27 positive reactive arthritis

OBJECTIVE—To study HLA class II association in reactive arthritis.
METHODS—63 patients with reactive arth-ritis and 46 with rheumatoid arthritis were included in the study. HLA-DR alleles were determined by using a sequence specific PCR method. Oligonucleotide hybridisation was used for definition of DRB1*04 subtypes and DQB1 alleles. HLA-B27 was determined by standard microcytotoxity test or by PCR. HLA-B27 subtyping was made by sequencing.
RESULTS—46 (73%) of 63 patients with reactive arthritis were HLA-B27 positive and 24 (38%) were HLA-DRB1*04 positive. When haplotypes were inferred according to the known associations between DRB1 and DQB1 alleles, the frequency of DRB1*04-DQB1*0301 haplotype was found to be 13% (12/92) in HLA-B27 positive reactive arthritis patients, in contrast to 0% in HLA-B27 negative reactive arthritis (P = 0.04) and 1% in random controls (P = 0.0009). However, this combination was also found in 5% of 84 HLA-B27 positive control haplotypes, showing a linkage disequilibrium between B27 and this particular class II haplotype. HLA-DRB1*0408 subtype was found in 8/24 (33%) of the HLA-DRB1*04 alleles in patients with reactive arthritis, accounting for most DQB1*0301 haplotypes, but only in 5/55 (9%) of the DRB1*04 alleles in random controls (P = 0.017). All reactive arthritis patients with this subtype were positive for HLA-B27. DRB1*04-DQB1*0302 haplotype was increased in patients with rheumatoid arthritis (28/92, 30%) compared with reactive arthritis (12/126, 10%) or with the controls (12/100, 12%; P = 0.003). HLA-B*2705 was by far the dominant B27 subtype both in reactive arthritis patients with the particular DRB1*0408-DQB1*0301 haplotype and in controls. It was found in 11 out of 12 DR analysed patients, as well as in 10 out of 11 randomly selected B27 positive controls.
CONCLUSIONS—Although no single class II allele was found to be increased among patients with reactive arthritis, HLA-B27, DRB1*0408, and DQB1*0301 might exert a haplotypic effect in the pathogenesis of reactive arthritis, or they may be markers of a subset of B27 haplotypes conferring susceptibility.

     

Association of class I, II, and III MHC gene products with systemic lupus erythematosus

Summary Class I, II, and III MHC gene products were examined in 248 Central European SLE patients. The previously reported association with HLA-A1, -B8 and -DR3, and C4AQ0 alleles was confirmed. The frequency of HLA-DR2 was also slightly elevated in SLE patients, while no increase in C4BQ0 alleles was observed. Additional findings were a significantly increased frequency of HLA-B13 and a significant decrease of HLA-B44.     

Analysis of HLA alleles polymorphism in Chinese patients with primary biliary cirrhosis

BACKGROUND: A familial dustering of patients with primary biliary cirrhosis (PBC) and the presence of immunological abnormalities in family members suggest a genetic component involved in the pathogenesis of PBC. The aims of this study are to investigate the frequencies of human leukocyte antigen HLA-A, -B, and -DRB1 alleles in Chinese patients with PBC by polymerase chain reaction (PCR)-based techniques, and to assess the correlation of the above-mentioned HLA with some clinical and laboratory features. METHODS: Genotyping of HLA alleles were performed in 65 well-characterized PBC patients and 431 healthy controls with sequence-specifc primers PCR amplification. RESULTS: HLA-DRB1~*07 allele detected in 19 of the 65 (29.2%) PBC patients was subtyped as DRB1~*0701, as well as in 13.9% of controls (P_C<0.05, OR=2.55, 95% CI: 1.4-4.6). An increased frequency of DRB1~*03 (18.4% vs. 7.2% in healthy controls) and a decreased frequency of DRB1~*12 (16.9% vs. 28.8%) in PBC patients were statistically significant. There was no association with HLADRB1~*08 reported. The frequencies for HLA-A, B and the other DRB1 alleles were similar between patients and healthy controls. CONCLUSIONS: The susceptibility to PBC in Chinese individuals is associated with DRB1~*0701 allele. This association differs from that in North Americans, South Americans, North Europeans and even Japanese, but it is not restricted to any particular subgroup of patients.     

Correlations between HLA-A, HLA-B and HLA-DRB1 allele polymorphisms and childhood susceptibility to acquired aplastic anemia

To investigate the correlations between polymorphisms of human leukocyte antigen (HLA)-A, HLA-B and HLA-DRB1 alleles and childhood susceptibility to aplastic anemia (AA), 80 children with AA were investigated. Among the 80 children, 74 had severe AA (SAA). Blood samples were collected from 109 healthy children as the controls. High-resolution genotyping of HLA-A, HLA-B and HLA-DRB1 alleles was conducted using polymerase chain reaction amplification with sequence-specific primers and polymerase chain reaction amplification with sequence-based typing. The expression frequencies of HLA-B*48:01 and DRB1*09:01 were significantly higher and the frequencies of HLA-B*51:01, DRB1*03:01 and DRB1*11:01 were significantly lower in the AA group compared with those in the control group. In addition, the frequencies of HLA-B*48:01 and DRB1*09:01 were significantly higher and the frequencies of HLA-B*51:01, DRB1*03:01 and DRB1*11:01 were significantly lower in the SAA group compared with those in the control group. HLA-B*48:01 and DRB1*09:01 were correlated with childhood AA, and thus they may be susceptibility genes for childhood SAA. HLA-B*51:01, DRB1*03:01 and DRB1*11:01 are expressed at low levels in children with AA.     

Molecular subtypes of the HLA-DR antigens in pulmonary tuberculosis.

OBJECTIVE: The aim of this study was to analyze association between HLA-DRB1 alleles and pulmonary tuberculosis (PTB) in the Polish population. METHODS: The HLA-DRB1 typing was performed using sequence-specific amplification (polymerase chain reaction with sequence specific primer [PCR-SSP] in 31 patients and 58 healthy volunteers. The DRB1 primers were supplied by DYNAL in the standard kit DYNAL DR "low-resolution"-SSP. RESULTS: The study showed that the DRB1*16 alleles frequency was higher in patients with PTB than in the tested group of healthy controls (P < 0.01). When HLA-DR2 alleles were combined (i.e., the DRB1*15 with DRB1*16 alleles), their frequency was comparable with that in the healthy individuals. The highest relative risk (RR) of tuberculosis was associated with DRB1*16 alleles (RR = 9.7). When HLA-DR6 alleles were combined (i.e., the DRB1*13 with DRB1*14 alleles), only a trend for higher frequency in patients with PTB was found. Frequency of DRB1*13 alleles of HLA-DR6 was significantly lower in PTB than in the healthy individuals (P < 0.001; RR = 0.04). CONCLUSIONS: Results suggest that the presence of HLA-DRB1*16 alleles may increase the risk of development of PTB, whereas HLA-DRB1*13 alleles may be resistant to tuberculosis.     

YMDD耐药变异与HLA等位基因多态性的相关性

目的：初步探讨慢性乙型肝炎(CHB)患者拉米夫定治疗中YMDD变异与HLA-A,B,DRB1各位点等位基因分布频率的相关性．方法：对142例CHB患者,采用荧光标记杂交双探针PCR融解曲线法(FH-PCR-MC)检测血浆HBV YMDD变异；对其中56例患者的外周血白细胞,采用序列特异性引物/聚合酶链式反应(PCR-SSP)技术检测人类白细胞表面抗原等位基因(HLA-A-B,DRB1)分型．结果：在用拉米夫定治疗的142例CHB患者中,YMDD变异率为56．3％．HLA-B~*58和DRB1~*03等位基因分布频率在YMDD变异组与YMDD野生组比较有显著性降低(0．013 vs 0．094,P=0．036；0．000 vs 0．063,P=0．024)；HLA-A~*30等位基因分布频率在YIDD组明显增高,与YVDD组比较差异显著(0．158 vs 0．024,P=0．034)；HLA-A~*33等位基因分布频率在YVDD变异组明显增高,与YIDD变异组比较差异显著(0．119 vs 0．000,P=0．028)．结论：YMDD耐药变异与HLA等位基因多态性有一定相关性．携有HLA-B~*58和DRB1~*03等位基因的个体感染的HBV可能不易发生YMDD变异；携有HLA-A~*30等位基因的个体感染的HBV可能易发生YIDD变异：携有HLA-A~*33等位基因的个体感染的HBV可能易发生YVDD变异．     

Association and frequency of HLA-A, B and HLA-DR genes in south Tunisian patients with spondyloarthritis (SpA)

The aim of this study is to investigate the association of HLA-A, B and HLA-DR gene expression and to assess an association of additional HLA antigens besides HLA-B27 in south Tunisian patients with spondyloarthritis (SpA). Eighty-five patients diagnosed with ankylosing spondylitis (AS, n=68) and reactive arthrithis (ReA, n=17) were selected and compared with 100 healthy controls (HC). HLA class I antigens were typed serologically using microlymphocytotoxicity technique. HLA-DRB1* alleles were studied by polymerase chain reaction amplification with sequence-specific primers. The significance of differences between patients and controls was tested by chi-square analysis. We found significantly increased frequencies of HLA-A3 (30.6%; pC=0.04; OR=2.95), HLA-B27 (62.35%; pC=4.10(-17), OR=53.55), and HLA-DRB1*15 (17.2%; pC=0.026; RR=2.58) alleles in SpA patients compared to HC. The most frequent and strongest association was observed for HLA-B27 in AS (pC=6.6 ×10(-16), OR=52.23). When AS and ReA patients were analysed separately, HLA-DRB1*15 and HLA-A3 were increased only in AS (pC=0.01, OR=2.99 and pC=0.03, OR=3.14, respectively). In ReA patients, HLA-DRB1*04 (p=0.033, pC=NS, OR=2.89) was found to be the most common allele. By analysing the HLA-B27-negative subgroup, HLA-A3 and HLA-DRB1*15 expression was found to be dependent on the presence of HLA-B27. HLA-B27 expression was higher in male (45/53; 85%) as compared to female (8/53; 15%) patients (p=0.03). Apart from HLA-B27, HLA-A3 and HLA-DRB1*15 are the MHC class I and II alleles found most frequent in Tunisian patients with AS, whereas HLA-DRB1*04 was found most frequent in ReA patients. HLA-B27 is more frequent in male than in female patients.     

原发性胆汁性肝硬化患者人类白细胞抗原等位基因多态性分析

目的探讨原发性胆汁性肝硬化(PBC)患者人群与人类白细胞抗原(HLA)Ⅰ类(A、B)、Ⅱ类(DRB1)等位基因的相关性,同时评估易感基因是否与一些临床及实验室特征存在联系。方法利用序列特异性聚合酶链反应(SSP-PCR)对65例确诊的PBC患者和431名健康人进行HLA—A、B和DRB1 等位基因以及有关基因亚型分析。结果PBC患者DRB1*07的频率增高到29.2%,与正常人13.9%的频率相比,差异具有统计学意义(Pc<0.05,OR=2.55,95%CI:1.4～4.6);所有DRB1*07阳性患者经亚型分析均为DRB1*0701。未发现DRB1*08与PBC有关联性。Ⅰ类抗原中以A*2在PBC患者组的频率最高(53.8%),稍高于对照组,但无统计学意义。其余HLA-A、B和DRB1的等位基因频率与正常人相比较,差异无统计学意义。DRB1*0701阳性患者与阴性患者在一些临床、实验室指标上差异并不明显。结论PBC与HLA-DRB1*0701基因相关,与南美、北美、北欧、日本等其他国家PBC患者的易感基因明显不同;HLA-DRβ1第78位上的缬氨酸残基可能与PBC发病相关。