30例重症肌无力患者人类白细胞抗原-Ⅱ基因多态性测定及分析

目的 探讨人类白细胞抗原（HLA）-Ⅱ基因多态性在贵州汉族人群重症肌无力（MG）发病中的作用。方法选择本地区汉族人群中30例MG患者（MG组）、36例神经内科非自身免疫性疾病患者（疾病对照组）及30例健康查体者（正常对照组）,采用PCR-序列特异性引物（PCR-SSP）技术进行HLA-Ⅱ类基因DRB1、DQB1位点分型,并对其与Mc的相关性进行分析。结果MG组HLA-DRB1＊0901和DQB1＊0303等位基因频率显著高于其他两组（P〈0．05）,DQB1＊0601等位基因频率显著低于其他两组（P〈0．05）。结论HIA-DRB1＊0901及DQB1＊0303可能为MC的易感基因,而HLA—DQ＊0601为保护基因。     

HLA-DRB1基因多态性与扩张型心肌病的相关分析

目的探讨扩张型心肌病（IDC）与人类白细胞抗原（HLA）-DRB1基因多态性的关系。方法用聚合酶链反应一序列特异性引物方法检测301例IDC患者（IDC组）与436例正常人（对照组）的HLA-DRB1等位基因分布情况。结果IDC组HLA-DRB1＊11、HLA-DRB1＊12、HLA-DRB1＊14的基因频率明显高于对照组（RR=2．91、4．02、3．78，P〈0．05）；IDC组同时携带HLA-DRB1＊12、DRB1＊14基因型的阳性率亦显著高于对照组（RR=6．24．P〈0．01）。结论HIA-DRB1＊11、DRB1＊12、DRB1＊14与IDC有明显相关性。     

HLA—DRB和ACE基因与肺结核的相关性分析

目的探讨人类白细胞抗原（HL气）-DRB基因和血管紧张素转换酶（ACE）基因多态性与肺结核的相关性。方法采用聚合酶链反应-序列特异性引物法（PCR—SSP）对肺结核组和健康对照组进行HLA-DRB和ACE基因分型。结果肺结核组HLA—DRB1＊15等位基因的频率显著高于对照组（P〈0．05）；复治和耐药肺结核组ACE基因的I／D基因型频率显著高于初治和无耐药组（P〈0．05）。结论HLA—DRB1＊15等位基因及ACE基因的I／D基因型与肺结核密切相关。     

GD药物引起粒细胞减少与等位基因的关系

采用多聚酶链式反应-序列特异引物（per—ssp）方法检测65例GD病人抗甲状腺药物引起粒细胞减少（1）组，65例GD病人并发粒细胞减少（2）组，65例非GD病人粒细胞减少（3）组，65例正常参照人群（4）组的HLA—DRB1＊08032 DRB1＊1501的等位基因频率。结果1：（1）组HLA—DRB1＊08032 DRB1＊1501的基因频率高于（2）组（P〈0．05）。2：（1）组HLA—DRB1＊08032 DRB1＊1501的基因频率明显高于（3）组（4）组，（P〈0．01）。3：（2）组HLA—DRB1＊08032 DRB1＊1501的基因频率高于（4）组（P〈0．05）。结论：GD病人应用抗甲状腺药物引起粒细胞减少与HLA—DRB1＊08032 DRB1＊1501等位基因频率增加有关。     

人类白细胞抗原—DRB1和DQB1基因与肺结核合并糖尿病的相关性分析

目的 探讨人类白细胞抗原（HLA）－DRB1手DQB1基因与肺结核合并2型糖尿病的关联性;寻找与肺结核合并2型糖尿病可能相关的HLA基因。方法 采用病例对照和聚合酶链反应－特异性序列引物（PCR－SSP)方法,对我国北方汉族123例肺结核合并2型糖尿病患者和与其无因缘关系的46名健康对照以及45全单纯2型糖尿病患者分别进行HLA－DRB1和DQB1闰点的等位基因分型。结果 肺结核合并2型糖尿病患者组中DRB1＊09基因频率明显高于健康人组,分别为25．10％和14．03％,RR为2．22,肺结核合并2型糖尿病患者组中DRB1＊09基因频率明显高于单纯2型糖尿病患者组,分别为25．10％和9．32％,RR为3．16,统计学上差异均有显著性;在肺结核合并Ⅱ型糖尿病患者组中DQB1＊05基因频率明显低于单纯2型糖尿病患者组,分别为7．17％和21．12％,RR为0．26,统计学差异有非常显著性。结论 研究提示DRB1＊09基因可能是肺结核合并2型糖尿病的易感基因;DQB1＊05基因可能是肺结核合并2型糖尿病的保护基因;可以推测DRB1＊09和DQB1＊05基因在肺结核合并2型糖尿病的发病中起一定作用,或是真正起作用的基因与它们连锁,有待于进一步研究。     

发作性睡病与HLA—DQB1＊0602基因的相关性研究

目的 探讨发作性睡病与HLA—DQB1基因的相关性。方法 对30例发作性睡病患者的临床资料进行分析。用序列特异性引物-聚合酶链反应（PCR-SSP）分型技术测定HLA—DQB1等位基因，并与44例健康人检测的数据进行比较。结果 发作性睡病患者组DQB1＊0602基因频率为40％，与正常对照组9．09％相比较明显增高；未检出DQB1＊0401—0402基因，与正常对照组9．09％相比较，经统计学分析，差异有显著性（P〈0．05）。结论 HLA—DQB1＊0602基因为中国发作性睡病人群的易感基因；HLA-DQB1＊0401—0402基因为中国发作性睡病人群的保护基因。     

山东籍汉族寻常型天疱疮与HLA-DRB1基因的相关性

目的 探讨HLA-DRB1位点基因在山东籍汉族寻常型天疱疮易感性中的作用.方法 用序列特异性引物-聚合酶链反应（PCR-SSP）方法,对61例寻常型天疱疮（PV）患者和70名正常对照者进行了HLA-DRB1等位基因的分型,并分析了DRB1基因在两组中的分布.结果 与正常对照组比较,PV患者组DRB1＊14（＊1401、＊1404、＊1405、DBR1＊0406）基因频率明显增高（P＜0.05）.结论 山东籍汉族PV主要与HLA-DRB1基因有关.     

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。     

肺结核病患者与HLA-DRBI等位基因的关联

目的：通过对湖北省汉族肺结核病（PTB）患者进行HLA-DRB1基因分型,探讨此人群与HLA-DRB1的相关性。方法：用序列特异性寡核苷酸探针聚合酶链反应（PCR-SSOP）技术对174例PTB患者及1358例健康人群进行HLA-DRB1基因分型。基因频率与Hardy-Weinberg平衡卡方检测使用arlequin软件进行,组间比较用Fisher精确概率法计算P值,检测水准为a=0．05,相对危险系数用RR表示,RR：A（A＋B）／C（C＋D）。结果：174例PTB患者HLA-DRB1基因分型结果与希望值进行H-W平衡检测（P〉0．05）。此人群检出HLA-DRB1等位基因共13种与对照组一致。其中RB1＊08与DRB1＊09基因频率显著高于对照组,差异有统计学意义（P〈O．01）,且RR〉1,说明DRB1＊08与DRB1＊09或与其连锁的单倍型可能是的PTB易感基因;RB1＊10与DRB1＊13基因频率显著低于对照组,差异有统计学意义（P〈0．05）,且RR〈1,说明RB1＊10与DRB1＊13可能是PTB的保护基因。其余等位基因频率组间比较均无统计学意义。结论：湖北省汉族PTB患者这个疾病群体遗传平衡被杂化,其与HLA-DRBl有一定的关联,但有其自身的特点。     

抗SSA和SSB抗体与HLA-Ⅱ基因的相关性分析

目的：探讨云南汉族系统性红斑狼疮（SLE）患者抗SSA和SSB抗体与HLA－DRB1、DQA1、DQB1等位基因及单体型的相关性。方法：采用多聚酶链反应－序列特异性引物（PCR－SSP）技术对63例云南汉族SLE患者和54名同民族健康对照进行DRB1、DQA1、DQB1基因分型。结果：云南汉族SLE患者中DR15（P＜0．01）、DR16（P＜0．05）、DQA1＊0102（P＜0．05）、DQA1＊0103（P＜0．01）、DQB1＊0601（P＜0．05）等位基因频率明显增高；抗SSA和SSB抗性阳性的SLE病人中DQA1＊0103频率均显著增高（P＝0．042，P＝0．006）；抗SSB抗体阳性的SLE患者中的DQA1＊0501 频率均显著增高（P＝0．009）。结论：云南汉族SLE 抗SSA和SSB抗体的产生与DQA1＊0103等位基因相关；抗SSB抗体的产生还与DQA1＊0501相关。     

新疆维吾尔族人群HLA-DR、DQ基因多态性与结核病易感性的研究

目的 探讨人类白细胞抗原(HLA)-DRB1、DQB1基因多态性与新疆维吾尔族人群结核病易感性的关联。 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226例新疆维吾尔族肺结核病患者(肺结核病例组)和231例新疆维吾尔族健康对照者(健康对照组)进行HLA-DRB1、DQB1基因分型,比较其等位基因频率(GF),并计算其比值比(OR)。 结果 1. 肺结核病例组中HLA-DRB1*11基因频率显著高于健康对照组,2组的GF分别为4.5%、1.1%,差异有统计学意义(OR=4.388,95%CI=1.618～11.905,P_c＜0.05);肺结核病例组中HLA-DRB1*04基因频率显著高于健康对照组,2组的GF分别为12.8%、8.4%,但P值经过校正后差异无统计学意义(OR=1.686,95%CI=1.060～2.684,P_c>0.05)。 2. 肺结核病例组中HLA-DQB1*0201基因频率显著高于健康对照组,2组的GF分别为40.1%、19.2%,差异有统计学意义(OR=3.379,95%CI=2.302～4.960,P_c＜0.05); 肺结核病例组中HLA-DQB1*0301/4基因频率显著低于健康对照组,2组的GF分别为6.2%、10.3%,但P值经过校正后差异无统计学意义(OR=0.561、95%CI=0.334～0.941,P_c＞0.05)。 结论 HLA-DRB1*11、DQB1*0201等位基因与新疆维吾尔族人群结核病强相关,DRB1*11、DQB1*0201可能是其易感基因。     

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.     

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。     

Association between HLA class Ⅱ gene and susceptibility or resistance to chronic hepatitis B

AIM: To investigate the association between the polymorphism of HLA-DRB1, -DQA1 and -DQB1 alleles and viral hepatitis B. METHODS: HLA-DRB1, -DQA1 and -DQB1 alleles in 54 patients with chronic hepatitis B, 30 patients with acute hepatitis B and 106 normal control subjects were analyzed by using the polymerase chain reaction/sequence specific primer (PCR/SSP) technique. RESULTS: The allele frequency of HLA-DRB1*0301 in the chronic hepatitis B group was markedly higher than that in the normal control group (17.31% vs 5.67 %), there was a significant correlation between them (X^2= 12.3068,PC=0.0074, RR=4.15). The allele frequency of HLA-DQAI*0501 in the chronic hepatitis B group was significantly higher than that in the normal control group (25.96 % vs 13.68 %), there was a significant correlation between them (X^2=9.2002, PC=0.0157, RR=2.87). The allele frequency of HLA-DQBI*0301 in the chronic hepatitis B group was notably higher than that in the normal control group (35.58 % vs 18.87 %), there was a significant correlation between them (x^2=15.5938, PC=0.0075, RR=4.07). The allele frequency of HLA-DRB1*1101/1104 in the chronic hepatitis B group was obviously lower than that in the normal control group (0.96 % vs 13.33 %), there was a significant correlation between them (X^2=11.9206, PC=0.0145, RR=18.55). The allele frequency of HLA-DQAI*0301 in the chronic hepatitis B group was remarkably lower than that in the normal control group (14.42 % vs30 %), there was a significant correlation between them (X^2=8.7396, PC=0.0167, RR=0.35). CONCLUSION: HLA-DRBI*0301, HLA-DQAI*0501 and HLA-DQBI*0301 are closely related with susceptibility to chronic hepatitis B, and HLA-DRB1*1101/1104 and HLA-DQAI*0301 are closely related with resistance to chronic hepatitis B. These findings suggest that host HLA class Ⅱ gene is an important factor determining the outcome of HBV infection.     

Association between HLA class Ⅱ gene and susceptibility or resistance to chronic hepatitis B

AIM: To investigate the association between the polymorphism of HLA-DRB1, -DQA1 and -DQB1 alleles and viral hepatitis B.METHODS: HLA-DRB1, -DQA1 and -DQB1 alleles in 54patients with chronic hepatitis B, 30 patients with acute hepatitis B and 106 normal control subjects were analyzed by using the polymerase chain reaction/sequence specific primer (PCR/SSP) technique.RESULTS: The allele frequency of HLA-DRB1*0301 in the chronic hepatitis B group was markedly higher than that in the normal control group (17.31% VS 5.67%), there was a significant correlation between them (χ2= 12.3068,Pc=0.0074, RR=4.15). The allele frequency of HLADQA1*0501 in the chronic hepatitis B group was significantly higher than that in the normal control group (25.96% VS 13.68%), there was a significant correlation between them (χ2=9.2002, PC＝0.0157, RR=2.87). The allele frequency of HLA-DQB1*0301 in the chronic hepatitis B group was notably higher than that in the normal control group (35.58%vs 18.87%), there was a significant correlation between them (χ2=15.5938, PC=0.0075, RR=4.07). The allele frequency of HLA-DRB1*1101/1104 in the chronic hepatitis B group was obviously lower than that in the normal control group (0.96% VS 13.33%), there was a significant correlation between them (χ2=11.9206, PC=0.0145, RR=18.55). The allele frequency of HLA-DQA1*0301 in the chronic hepatitis B group was remarkably lower than that in the normal control group (14.42% VS30%), there was a significant correlation between them (χ2=8.7396, Pc=0.0167, RR=0.35).CONCLUSION: HLA-DRB1*0301, HLA-DQA1*0501 and HLA-DQB1*0301 are closely related with susceptibility to chronic hepatitis B, and HLA-DRB1*1101/1104 and HLADQA1*0301 are closely related with resistance to chronic hepatitis B. These findings suggest that host HLA class Ⅱ gene is an important factor determining the outcome of HBV infection.     

人类白细胞抗原-DR及-G基因多态性与广西儿童哮喘发病的研究

目的探讨人类白细胞抗原（HLA）．DR及．G基因多态性与儿童哮喘的关系。方法以无血缘关系的84例哮喘儿童为哮喘组,168名无哮喘和特应性疾病的健康个体为对照组。采用PharmaciaUniCAP系统检测哮喘儿童的血清总IgE水平。应用基因芯片法检测HLA．DR的21个基因位点和基于基质辅助激光解吸电离-飞行时间质谱技术（MALDI-TOF）检测HLA-G的9个单核苷酸位点。结果（1）儿童哮喘组HLA-DRB1＊070X基因和HLA-DRB1＊11XX基因频率分别为2．98％和13．69％,对照组分别为0．3％和5．95％C=6．915,P〈0．05;X2=9．478,P〈0．01）。优势比（OR）分别为10．57（95％CI：1．215～91．986）和2．79（95％CI：1．429～5．449）。HLA—DRB3（52）＊010X基因频率在哮喘组为7．14％,低于对照组的13．99％（X2=5．854,P〈0．05）,OR为0．429（95％CI：0．214～0．862）。（2）HLA—DRB1＊15XX．HLA-G的rsl704和rsl063320位点的14bp缺失-G单体型（HLA—DRB1＊15XX．14bp缺失-G）携带者哮喘风险比未携带者降低（Wald值为13．419,P〈0．001）,锨值为0．198,95％CI为0．084—0．471;哮喘组中携带该单体型者血清IgE水平（365．0±943．1）KU／L,也较未携带者（977．8±14334．9）KU／L为低,差异有统计学意义（P〈0．05）。结论HLA．DRB1＊070X基因和HLA—DRBl‘11XX基因与儿童哮喘易感性相关,HLA．DRB3（52）＊010X基因可能为保护性基因,HLA—DRB1＊15XX和HLA-G的rs1704和rs1063320位点的14bp缺失-G单体型是哮喘的保护性单体型。     

HLA-DRB1＊14和＊15等位基因与肝癌的相关性

目的探讨HLA-DRB1＊14和＊15等位基因与肝癌发生的相关性。方法以40例原发性肝癌患者作为病例组,以135例健康人作为对照组,应用PCR-SSP方法对研究对象外周血的HLA-DRB1等位基因进行检测,分析其表达与原发性肝癌的相关性。结果 HLA-DRB1＊14在病例组中的分布频率较对照组显著增高（χ2=9.925,P=0.002,OR=3.450,95%CI：1.555～7.655）,HLA-DRB1＊15在病例组和对照组中的分布频率的差异无统计学意义（χ2=1.260,P=0.262,OR=1.538,95%CI：0.723～3.274）。结论 HLA-DRB1＊14可能是原发性肝癌的易感基因,HLA-DRB1＊15可能与原发性肝癌的发生无明显关系。     

Association of HLA DRB1-DQA1-DQB1 haplotypes with rheumatic heart disease in Taiwan

This case-control study was carried out to investigate the possible relationship between the gene frequencies of HLA-DRB1, -DQA1 and -DQB1 alleles/haplotypes and rheumatic heart disease (RHD) among the Chinese population in Taiwan. A group of 115 patients with RHD documented by echocardiography, and a group of 115 normal controls were studied. The HLA-DRB1, -DQA1 and -DQB1 allele frequencies were determined by polymerase chain reaction and sequence-specific oligonucleotide probe. As compared with controls, patients with RHD had an increased frequency of DR11-05-DQ7 haplotype and a decreased frequency of DR4-03-DQ4 haplotype. The frequencies of DRB1, DQA1 or DQB1 alleles were not significantly different between RHD patients and controls. Further categorization of RHD patients into mitral valve disease and combined valve disease subgroups revealed no statistical difference in these alleles when compared with the two subgroups. Patients with RHD have a higher frequency of DR11-05-DQ7 haplotype and a lower frequency of DR4-03-DQ4 haplotype, which indicates that certain HLA DRB1-DQA1-DQB1 haplotypes in determining the risk/protection of RHD in Taiwan Chinese.