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。     

HLA-DR单倍型与中国南方汉族肺结核的相关性分析

目的　探讨HLA DR基因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 23个HLA DR等位基因进行分型 ,比较两组间DR53-DRB1、DR52-DRB1和DR51-DRB1单倍型频率 (HF)并计算其相对危险性(RR)。结果 DR16-DR52单倍型的频率肺结核病例组显著高于对照组 (0.01<P<0.05),其RR为3.10;DR1-DR53、DR1-DR52、DR13.3-DR53、DR12-DR53、DR13.3-DR52、DR7-DR52.DR9-DR52单倍型的频率肺结核病例组显著低于对照组（前四者P<0.01,后三者 0.01<P<0.05),其 RR分别为 0.29、0.26、0.38、0.52、0.25、0.10、0.42。结论DR12-DR53、DR7-DR52、DR9-DR52单倍型的存在可能与中国南方汉族肺结核的发病有关联,而其它单倍型的差异则可能是因其组成基因的基因频率差异所致。     

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-DR-DQ单倍型与类风湿关节炎的关系

目的　探讨HLA -DR -DQ单倍型与我国汉族类风湿关节炎 (RA)的相关性。方法　以 10 0名健康人为对照 ,采用PCR -RFLP法对汉族人群中 35例RA患者的DRBl、DRB3、DRB5、DQAl和DQBl基因位点多态性进行分析。结果　DRBl 0 4 0 5 -DQAl 0 30 1-DQBl 0 4 0 1单倍型频率在RA患者明显高于正常人 (分别为14 0 %和 4 5 % ,P <0 0 1) ,该单倍型阳性RA患者的病情重于其它RA患者 ,包括关节肿胀数、晨僵时间、RF滴度和病情严重例数在阳性组明显高于阴性组 (P均 <0 0 5 ) ;而DRBl 15 0 1-DRB5 0 10 1-DQAl 0 10 2 -DQBl 0 6 0 2单倍型频率在正常人明显高于RA患者 (分别为 12 %和 4 3% ,P <0 0 1)。结论　DRBl 0 4 0 5 -DQAl 0 30 1-DQBl 0 4 0 1单倍型与RA发病及病情严重程度相关 ;而DRB1 15 0 1-DRB5 0 10 1-DQA1 0 10 2 -DQBl 0 6 0 2单倍型则可能对易患RA起保护作用     

山东地区类风湿关节炎与HLA-DRB1基因共同表位的关联性研究

目的　探讨山东地区汉族人群类风湿关节炎 (RA)与HLA DRB1基因共同表位 (SE)的关联性。方法　采用特异性引物聚合酶链反应 (PCR SSP)方法对山东地区人群 1 32例RA患者及1 30名正常健康者的HLA DRB1 0 1、 0 4、 1 0的 1 7个等位基因进行检测。结果　山东地区RA患者中携带有SE的基因频率显著高于正常对照组 (5 0 0 %∶2 2 3% ,P <0 0 1 ) ,HLA DR4亚型 0 4 0 5是主要的易感基因 (2 2 8%∶1 0 0 % ,P <0 0 0 5 )。其他亚型包括DRB1 0 1 0 1 (3 8%∶3 1 % ) , 0 1 0 2 (2 3%∶2 3% ) , 0 1 0 3(3 8%∶3 1 % ) , 0 1 0 4 (3 0 %∶2 3% ) , 0 4 0 1 (1 0 6 %∶4 6 % ) , 0 4 0 4 (9 1 %∶4 6 % ) , 0 4 0 7(8 3%∶9 2 % ) , 0 4 0 3(6 8%∶3 1 % ) , 0 4 0 2 (6 8%∶4 6 % ) , 0 4 0 8(5 3%∶1 5 % ) , 0 4 0 9(2 3%∶0 ) , 0 4 0 6 (1 5 %∶0 ) , 0 4 1 0 (0 8%∶0 ) , 0 4 1 1 (0 8%∶0 )和 1 0 0 1 (1 1 4 %∶6 9% )的差别均无统计学意义。Logistic回归分析表明 :SE纯合子对RA的危害性要比其杂合子大 (P <0 0 0 1 )。结论　SE与山东地区汉族RA易感性及疾病严重性有关联     

HLA-DR.DQ基因与骨关节结核的易感性研究

目的 探讨HLA-DR.DQ基因多态性与骨关节结核的遗传关联性,比较骨关节结核与肺结核之间易感基因的差异。方法 采用聚合酶链反应-序列特异性引物 (PCR-SSP)方法,对86例骨关节结核,88例正常人及34例肺结核的HLA-DR.DQ等位基因进行分析。结果 骨关节结核组与正常人比较,骨关节结核组DRB109、DQB10301基因频率增高 (38.99%比8.24%　PC ＜0.0001　RR =8.92;18.27%比2.66%　PC ＜0.05　RR =2.21),DRB113.2基因频率显著低于对照组 (4.76%比20.50%　PC ＜0.001　RR =0.18)。骨关节结核组与肺结核比较,DRB109、DQB10301基因频率增高 (38.99%比9.2%　PC ＜0.0001;18.15%比1.85%　PC ＜0.001),而DRB115基因频率低于肺结核组 (17.17%比36.3%　PC ＜0.01)。结论 HLA-DRB109、DQB10301可能是我国骨关节结核的易感基因,DRB113.2为保护基因。骨关节结核与肺结核之间易感基因存在差异。     

支气管哮喘与HLA-DRB_1等位基因关联的研究(摘要)

人类第6号染色体上HLA区域的DP、DQ和DR位点在抗原呈递过程中起关键作用，因此影响免疫反应的特异性。已经证实，多种疾病，尤其是自身免疫疾病和过敏性疾病与HLA-Ⅱ类分子有关联。DR基因包括DRB1、DRB2、DRB3、DRB4、DRB5、DRB6、DRB7、DRA等。其中，DRB1座位有多达124个等位基因，多态性最为复杂。本研究旨在探讨HLA—DRB1等位基因与支气管哮喘的关系。材料与方法外源性哮喘患者46例，内源性哮喘患者52例，71例非过敏体质的本地区正常人作为正常对照。各取3～5ml外周血，EDTA抗凝，抽提基因组DNA；根据1992年发表的…     

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。     

中国人群1型糖尿病HLA-DQ基因多态性的Meta分析

目的　综合评价中国人群HLA DQ基因多态性与 1型糖尿病 (DM)的关联性。方法　以 1型DM组和健康对照组的各HLA DQ等位基因频数(基因型频数、单倍型频数 )分布的OR值为统计量,全面检索相关文献;应用Meta分析软件包REVMAN4. 2,在基因分型水平上,对各研究的结果进行一致性检验和数据合并,并评估发表偏倚。结果　等位基因DQA1* 0301、DQA1* 0501、DQB1* 0201、DQB1* 0303、DQB1* 0401和DQB1* 0604是中国人群 1型DM的危险基因 (均P<0. 05), 他们的合并OR值分别为2. 83、2. 90、4. 17、1. 65、2. 00和 3. 00;基因型 (或单倍型 )DQA1* 0301 /DQB1* 0201、DQA1* 0301 /DQB1*0302、DQA1* 0501 /DQB1* 0201、DQA1* 0301 /DQB1* 0201 /DRB1* 0301和DQB1* 0302 /DRB1* 0405是中国人群 1型DM的危险基因型(或单倍型,均P<0. 05),他们的合并OR值分别为 8. 95、3. 09、6. 01、6. 57和 14. 85。而等位基因DQA1* 0101、DQA1* 0102、DQA1* 0103、DQA1* 0104、DQA1* 0201、DQA1* 0401、DQA1* 0601、DQB1* 0301、DQB1* 0501、DQB1* 0503、DQB1* 0601和DQB1* 0602是中国人群 1型DM的保护等位基因(均P<0. 05),他们的合并OR值分别为 0. 47、0. 38、0. 21、0. 07、0. 44、0. 39、0. 44、0. 19、0. 33、0. 32、0. 42和 0. 28; 基因型     

蒙汉族儿童过敏性紫癜临床特点与HLA-DRB1基因关联性对比分析

目的　探索内蒙古地区蒙、汉族儿童过敏性紫癜 (AP)临床特点的不同与HLA DRB1等位基因的关联性。方法　选择祖籍三代居住内蒙古地区 ,无血缘关系、与异族通婚史及其他风湿性疾病史和家族史的蒙、汉族儿童AP 5 7例和 74例。比较临床特点 ,引入PCR SSP技术 ,分析HLA DRB1等位基因的型别 ,结合检索查新分析讨论。结果　①汉族病例组肾、心、多器官损害、肾病综合征、肾病综合征伴肾炎综合征损害率分别为 5 4 %、30 %、73%、12 %和 15 % ;比蒙古族相应损害率为 35 %、5 %、4 2 %、0和 0增高 (χ2 值分别是 4 6 6 6、12 4 82、12 736、—和— ,P分别为 0 0 31、0、0、0 0 0 5和 0 0 0 2 )。蒙古族平均住院 (18± 7)d ,比汉族 (2 7± 18)d短 ,(t′ =2 4 5 0 ,P =0 0 2 1)。②蒙古族病例组DRB1 110x基因频率为 13 2 % ,高于对照组 6 1% (χ2 =4 378,P =0 0 36 ) ,OR =2 386 ,95 %可信区间为 1 0 4 5～ 5 4 4 7。汉族病例组DRB1 0 10x基因频率为 14 6 % ,高于对照组4 8% (χ2 =10 0 7,P =0 0 0 2 ) ,OR =3 4 36 ,95 %可信区间为 1 5 4 3～ 7 6 5 2 ;而DRB1 0 80x基因频率为 2 7% ,低于对照组 8 7% (χ2 =5 2 4 ,P =0 0 2 2 )。并得出OR =0 337,95 %可信区间为 0 12 0～0 94 7。③汉族病     

Evidence of a Genetic Basis for the Different Geographic Occurrences of Liver/Kidney Microsomal Antibody Type 1 in Hepatitis C

Antibodies to liver/kidney microsome type 1 occur in Italian patients with hepatitis C, but rarely develop in North American patients. Our goals were to compare the frequencies of the HLA markers associated with autoimmune expression in Italian and North American patients with chronic hepatitis C and to determine genetic bases for regional differences in antibody production. HLA B8, DR3, DR4, DR7, DR11, DR13, DQ2, and the B8-DR3-DQ2 haplotype were determined by microlymphocytotoxicity and polymerase chain reaction in 105 Italian patients (50 with microsomal antibodies), 100 North American patients (none with microsomal antibodies), and Italian and North American healthy control subjects. Italian patients with microsomal antibodies differed from North American patients without these antibodies by having a higher frequency of HLA DR7 (54% vs. 27%, P=0.002). HLA DR7 occurred more frequently in seropositive Italian patients than in seronegative counterparts (54% vs. 11% P < 0.0001), Italian healthy control subjects (54% vs. 29%, P=0.0009), and North American healthy control subjects (54% vs. 19%, P < 0.0001). The frequency of HLA DR7 was similar in North American patients and controls (27% vs. 19%, P=0.2), but it was lower than in Italian controls (19% vs. 29%, P=0.059). Seropositive Italian patients had a lower frequency of HLA DR11 than seronegative Italian patients and Italian controls (18% vs. 34%, P=0.07, and 18% vs. 35%, P=0.02, respectively). In contrast to seropositive Italian patients, North American patients had HLA DR4 (30% vs. 12%, P=0.02), HLA DR13 (29% vs. 10%, P=0.01), and the B8-DR3-DQ2 haplotype (23% vs. 6%, P=0.01) more often. Similarly, HLA DR4 and the B8-DR3-DQ2 phenotype were more frequent in North American patients than in Italian controls (30% vs. 16%, P=0.005, and 23% vs. 7%, P=0.00002, respectively). HLA DR7 is associated with the development of microsomal antibodies in Italian patients with chronic hepatitis C. The lower frequency of HLA DR7 in North America could contribute to the rarity of these antibodies in this region. HLA DR11 may be protective against the development of microsomal antibodies in Italian patients, whereas HLA DR4, HLA DR13, and the B8-DR3-DQ2 haplotype may be protective in North American patients.     

Association between HLA-DQB1 gene and patients with acute lymphoblastic leukemia (ALL)

Acute lymphoblastic leukemia (ALL) affects both children and adults. Survival in ALL has improved in recent decades due to recognition of its biological heterogeneity. Although children have higher remission and cure rates than adults, both populations have benefited from these improvements. Our aim in this study is to determine the association between HLA-DQB1 genes with childhood and adult ALL patients. To define this association, we compared HLA-DQB1 allele frequencies and allele carrier frequencies in a cohort of 135 adults and children with ALL with 150 controls, using polymerase chain reaction with sequence-specific primers. Allele carrier frequencies in childhood ALL show a deficiency in DQ2 (*0201) (P 0.049 and RR 0.75), but an increase in DQ5 (*0501-*0504) and DQ7 (*0301, *0304) compared to the control group (P 0.001 RR 1.89, P 0.003 RR 1.48, respectively). Allele carrier frequencies in adult ALL indicated an increase in DQ5 (*0501-*0504) (P0.045 RR 2.28). Allelic frequencies in childhood ALL revealed the same increase in DQ5 and DQ7, and a decrease in DQ2. In adult ALL it shows a decrease in DQ7. Therefore, our results in adult ALL were similar to childhood ALL addressing DQ5 allele carriers, which showed an increase in both age groups. We suggest that DQ5 could be more strongly considered as an ALL susceptibility allele, and that this allele may underlie a pathogenic phenotype with a major role in the immunologic process involved in both adults and children with ALL.     

HLA DRB10405-DQB10401 haplotype is associated with autoimmune pancreatitis in the Japanese population

BACKGROUND & AIMS: Autoimmune pancreatitis is a distinctive disease entity characterized by high serum immunoglobulin G4 concentrations. Because of the close association between some autoimmune diseases and particular alleles of major histocompatibility complex genes, we investigated the association between HLA alleles and autoimmune pancreatitis. METHODS: HLA-A, -B, -C, -DR, and -DQ gene typing and HLA-DRB1, -DQB1, and -DPB1 allele typing were performed by the polymerase chain reaction sequence-specific primers method and the restriction fragment length polymorphism method, respectively, in 40 patients with autoimmune pancreatitis, 43 patients with chronic calcifying pancreatitis, and 201 healthy subjects. RESULTS: In patients with autoimmune pancreatitis compared with healthy subjects, we found a significant increase in DR4 (73% vs. 44%, corrected P = 0.01) and DRB1*0405 (58% vs. 21%, corrected P = 0.000026) and DQ4 (58% vs. 26%, corrected P = 0.001) and DQB1*0401 (58% vs. 21%, corrected P = 0.000017). The DRB1*0405-DQB1*0401 haplotype in autoimmune pancreatitis showed no significant association with any HLA class I antigens, in contrast to the B54-DRB1*0405-DQB1*0401 haplotype reported in autoimmune hepatitis. The frequencies of DRB1*0405 and DQB1*0401 were significantly high in patients with autoimmune pancreatitis compared with chronic calcifying pancreatitis. CONCLUSIONS: It is probable that DRB1*0405-DQB1*0401 haplotype is associated with autoimmune pancreatitis in the Japanese population.     

血HLA-A、-B、-C、-DRB1、-DQB1 等位基因多态性与肝细胞癌发生关联研究*

目的 探讨中国广东汉族人血HLA-A、-B、-C、-DRB1、-DQB1等位基因与HBV感染罹患肝细胞癌（HCC）的关联性。方法 采用聚合酶链反应-直接测序分型法检测广东地区56例HCC患者和97例健康志愿者血HLA-A、-B、-C、-DRB1、-DQB1基因型。结果 HCC患者血HLA- A*02:03和A*02:07等位基因频率明显高于健康人（0.116071对0.046392和0.178571对0.061856,x²=5.167、x²=10.33,P=0.023、P=0.001）;HCC患者血HLA-B*46:01等位基因频率为0.205357,明显高于健康人的0.108247（x²=5.439,P=0.02）;HCC患者血HLA- DRB1*14:54 和 DRB1*12:02等位基因频率明显高于健康人（0.089286对0和0.142857对0.06701,x²=14.502、x²=4.761,P=0.000、P=0.026）;HCC患者血HLA-DQB1*05:03等位基因频率为0.098214,明显高于健康人的0.036082（x²=4.951,P=0.026）;HCC患者血HLA-A*30:01等位基因频率为0.017857,明显低于健康人的0.082474（x²=5.355,P=0.021）;HCC患者血HLA-B*13:02等位基因频率为0.008929,明显低于健康人的0.07732（x²=6.702,P=0.01）。结论 在中国广东地区人群中,HLA-A*02:03、A*02:07、HLA-B*46:01、HLA-DRB1*14:54、DRB1*12:02、HLA-DQB1*05:03与感染HBV的HCC发病有关,而与HLA-A*30:01和HLA-B*13:02可能无关。     

Association analysis about HLA-DRB1, -DQB1 polymorphism and auto-antibodies against α(1)-adrenergic receptors in Chinese patients with essential hypertension

The auto-antibodies against α(1)-adrenergic receptors (α(1)-AAs) with agonist activity likes norepinephrine have been discovered in patients with essential hypertension but the mechanism of α(1)-AA production remains unclear. We supposed the α(1)-AAs be correlated to the HLA-DQB1 and DRB1 alleles. Three hundred ninety-six patients with essential hypertension (EH) and 224 normotensives were enrolled, and DNA typing was detected by protein coupled receptor (PCR) amplification with sequence-specific primers. Analysis was performed by α(2) and logistic regression. There were the significant associations of the haplotype HLA-DQB1*0301-DRB1*04 with the prevalence of α(1)-AAs in hypertensive patients and it obviously added to the risk for the α(1)-AA production (adjusted P = 0.019, OR 4.037, 95% CI 1.259-12.947). In normotensives, the haplotype HLA-DQB1*05-DRB1*04 provided a strong predisposition in α (1)-AAs production (adjusted P = 0.024, OR 3.922, 95% CI 1.200-12.817). These results suggest the HLA-DRB1*04 might be the primary risk alleles associated with α(1)-AA production on the haplotypes HLA-DQB1*0301-DRB1*04 and HLA-DQB1*05-DRB1*04 and increased the risk for α (1)-AA production.     

Association Analysis about HLA-DRB1, -DQB1 Polymorphism and Auto-Antibodies Against α1-Adrenergic Receptors in Chinese Patients with Essential Hypertension

The auto-antibodies against α₁-adrenergic receptors (α₁-AAs) with agonist activity likes norepinephrine have been discovered in patients with essential hypertension but the mechanism of α₁-AA production remains unclear. We supposed the α₁-AAs be correlated to the HLA-DQB1 and DRB1 alleles. Three hundred ninety-six patients with essential hypertension (EH) and 224 normotensives were enrolled, and DNA typing was detected by protein coupled receptor (PCR) amplification with sequence-specific primers. Analysis was performed by α² and logistic regression. There were the significant associations of the haplotype HLA-DQB1**0301-DRB1**04 with the prevalence of α₁-AAs in hypertensive patients and it obviously added to the risk for the α₁-AA production (adjusted P == 0.019, OR 4.037, 95%% CI 1.259–12.947). In normotensives, the haplotype HLA-DQB1**05-DRB1**04 provided a strong predisposition in α ₁-AAs production (adjusted P == 0.024, OR 3.922, 95%% CI 1.200–12.817). These results suggest the HLA-DRB1**04 might be the primary risk alleles associated with α₁-AA production on the haplotypes HLA-DQB1**0301-DRB1**04 and HLA‐‐DQB1**05-DRB1**04 and increased the risk for α ₁-AA production.     

Association of MHC class I related gene B (MICB) to celiac disease

BACKGROUND AND AIMS: Celiac disease (CD) is an enteropathic disorder characterized by strong association with HLA-DQ2. Our aim was to investigate whether MICB, a gene located in the MHC class I region, may contribute to CD susceptibility. PATIENTS AND METHODS: Total of 133 CD patients, previously reported to be associated with MICA-A5.1, and 116 controls were initially analyzed. Twenty-eight additional DQ2-negative CD patients were also studied. MICB was typed by PCR using sequence-specific primers. HLA-B, -DRB1, -DQA1, -DQB1, and MICA were also typed. RESULTS: The allele MICB0106 was strongly associated with CD (pc < 0.000001, odds ratio (OR) = 5.6, 95% confidence interval (CI) = 3.1-10.1) and it was overrepresented in atypical patients compared with typical ones (pc = 0.04, OR = 2.9, CI = 1.4-6.1). MICB0106 was part of DR3-DQ2 haplotype (B8-MICA-A5.1-MICB0106-DR3-DQ2), and consequently a strong linkage disequilibrium between MICB0106 with DQ2 (lambdas = 1) and MICA-A5.1 (lambdas = 0.55) was found. To analyze whether the association of MICB is independent of this haplotype, its association was also studied in DQ2-negative patients (n = 46). DQ8 (28%vs 9%, p = 0.0085, pc = NS) and MICB0104 (52%vs 30%, p = 0.01, pc = NS) were increased in DQ2-negative patients. MICA-A5.1 was significantly increased in atypical patients (p(c)= 0.001, OR = 6.4, CI = 2.2-18.4), and this association was independent of DQ2 and DQ8 (pc = 0.02, OR = 2.6, CI = 1.1-6.1). CONCLUSIONS: The expression of MIC genes on enterocytes under stressful conditions and their function as ligands of intraepithelial gammadelta and CD8 T cells, together with the data presented here suggest a potential role of MIC genes in the pathogenesis of CD.     

Distribution and frequency of HLA alleles and haplotypes in Brazilians with type 1 diabetes mellitus

The genetic predisposition to type 1 diabetes (DM1) is associated with genes of the human leukocyte antigen (HLA) system, specially the HLA-DR and -DQ. In Caucasians, the HLA-DR3 and -DR4 antigens are associated with susceptibility and the -DR2, with protection. In Brazil, a country with a large miscegenation of European Caucasians, Native Amerindians and African Blacks, the genetic basis of DM1 has not been adequately studied. The aim of this paper is to present a critical review of articles indexed in the MEDLINE and LILACS-BIREME data basis about the association of HLA with DM1 in Brazilians. Eight papers, all of them from the Southeast region, were found. Immunogenetic susceptibility to DM1 in Brazilians was associated with HLA-DRB1*03, -DRB*04, -DQB1*0201, -DQB1*0302 alleles, and protection against DM1 was associated with HLA-DQB1*0602, -DQB1*0301 alleles and -DR2 and -DR7 antigens. Since the Brazilian population is not racially homogeneous, it is not possible to extrapolate studies from a single region to the remainder of the country. It is necessary to study populations from different regions to identify new associations or to strengthen associations with the ones already identified. This knowledge will contribute to future prophylactic or therapeutic interventions in the group of Brazilians at risk of developing DM1.     

HLA class II allele and haplotype frequencies in Iranian patients with leukemia

Previous studies demonstrated significant differences in a number of HLA allele frequencies in leukemia patients and normal subjects. In this study, we have analyzed HLA class II alleles and haplotypes in 110 leukemia patients (60 acute myelogenous leukemia "AML", 50 chronic myelogenous leukemia"CML") and 180 unrelated normal subjects. Blood samples were collected from all of the patients and control subjects. DNA was extracted by salting out method and HLA typing was performed using PCR-SSP method. Significant positive association with AML was obtained for HLA-DRB1*11allele (35% vs. 24.7%, P=0.033). Two alleles including HLA-DRB4 and -DQB1*0303 were significantly less frequent in AML patients than in controls. HLA-DQB1*0303 allele was never observed in CML patients compared with allele frequency in controls (4.2%). According to haplotype analysis, HLA-DRB1*0101/DQA1*0104/-DQB1*0501 frequencies were significantly higher and -DRB1*16/-DQA1*01021/-DQB1*0501 frequencies were significantly lower in CML patients than in controls. In conclusion it is suggested that HLA-DRB1*16 allele and HLA-DRB1*15/-DQA1*0103/-DQB1*06011 and -DRB1*16/-DQA1*01021/-DQB1*0501 haplotypes predispose individuals to AML and HLA-DRB4 allele predispose to CML. Future studies are needed to confirm these results and establish the role of these associations in AML and CML.