海南地区女性HLA-DQB1和DRB5基因多态性与宫颈癌易感性的关系

目的 探讨海南地区汉族女性人群中人类白细胞抗原(HLA)-DQB1和HLA-DRB5等位基因多态性与宫颈癌易感性的相关性.方法 以海南地区41例经病理确诊的宫颈癌患者和38例因子宫肌瘤行全子宫切除术且病理证实无宫颈癌的患者为研究对象.采用PCR克隆测序技术对两组HLA-DQB1和DRB5等位基因进行分型.结果 共检测到12种HLA-DQB1等位基因和8种HLA-DRB5等位基因.其中HLA-DQB1*06011,HLA-DQB1* 030101和HLA-DQB1* 03032与HLA-DRB5* 01:01:01分别是海南地区汉族女性HLA-DQB1和DRB5的优势表达基因.无宫颈癌患者HLA-DRB5*0206等位基因频率(18.4％)显著高于宫颈癌患者(0)(P=0.013).结论 HLA-DRB5* 0206可能是海南地区女性宫颈癌的保护基因,可能降低女性患宫颈癌的风险.HLA-DRB5不同等位基因可能与宫颈癌的发生存在相关性.     

昆明汉族人群HLA-DRB1、DQB1基因多态性分析

目的研究昆明汉族HLA-DRB1、DQB1基因的多态性,探讨其在昆明汉族人群中的遗传特征.方法应用PCR-SSP基因分型技术,对云南昆明地区72名汉族健康儿童进行了HLA-DRB1、DQB1位点的基因分型.结果在昆明汉族,HLA-DRB1位点共检出了12种等位基因,其中以HLA-DRB1*12(20.14%)、DRB1*0901(19.44%)、DRB1*04(18.06%)较常见,其他基因频率大于10%的等位基因还有HLA-DRB1*08(11.11%)、DRB1*15(10.42%);在DQB1位点共检出了7种等位基因,其中以HLA-DQB1*0301(27.08%)、DQB1*06(21.53%)较常见,其他基因频率大于10%的等位基因还有HLA-DQB1*0303(15.97%)、DQB1*05(13.19%).昆明汉族分别与南方汉族、北方汉族HLA-DRB1、DQB1分布进行了比较,均有明显的差异(P<0.001).结论昆明汉族HLA基因分布特点既不同于南方汉族人群,也不同于北方汉族人群,具有独特性.可能与复杂的民族迁移历史和民族融合及云南独特的地理环境有关.     

中国汉族人群系统性红斑狼疮与HLA—DQB1基因关联性研究的Meta分析

目的:探讨中国汉族人群系统性红斑狼疮(SLE)与HLA-DQB1基因的关联情况.方法:检索已发表的有关中国汉族人群SLE和HLA-DQB1关联研究的文献,剔除不符合要求的文献,应用Revman4.1软件进行一致性检验和数据合并.结摹:等位基因DQB1*0502、DQB1*0601可能是中国汉族人群SLE患者的危险基因(P<0.05);等位基因DQB1*0301、DQB1*0302和DQB1*0401可能是中国汉族人群SLE患者的保护基因(均P<0.05).结论:中国汉族人群SLE与HLA-DQB1的某些等位基因具有关联性,且与其他种族人群有差异.     

HLA-DRB1和HLA-DQB1基因多态性与天疱疮的相关性

目的探讨人白细胞抗原(HLA)-DRB1和HLA-DQB1等位基因多态性与天疱疮的遗传相关性。方法以上海地区的58例天疱疮患者(病例组)和89名正常对照者(对照组)作为研究对象。采用聚合酶链反应-序列特异性引物分型技术(PCR-SSP)对两组HLA-DRB1和HLA-DQB1等位基因进行分型,直接计数法计算等位基因频率并进行组间比较,以等位基因频率的比值比(OR)评价基因与疾病的关联性。结果病例组和对照组共检测到13种HLA-DRB1等位基因和5种HLA-DQB1等位基因。统计学分析结果表明:病例组HLA-DRB1*14和HLA-DQB1*05等位基因频率分别为17.24%和18.97%,显著高于对照组的1.69%(P=0.000,P值的校正值Pc<0.05,OR=12.150)和6.74%(P=0.001,Pc<0.05,OR=3.238);病例组HLA-DQB1*06等位基因频率为15.52%,显著低于对照组的30.90%(P=0.003,Pc<0.05,OR=0.411)。结论 HLA-DRB1*14和HLA-DQB1*05可能是上海地区天疱疮患者的易感基因,而HLA-DQB1*06则可能是保护基因。     

遵义汉族人群HLA-DQB1等位基因多态性研究

目的从基因水平调查遵义汉族人群HLA-DQB1等位基因频率，并了解其多态性分布状况。方法应用聚合酶链反应-序列特异性引物（PCR-SSP）方法对遵义汉族109名健康人群进行等位基因分型。结果检出14个HLA-DQB1等位基因，遵义汉族人HLA-DQB1等位基因频率分布为HLA-DQB1＊0303〉＊0301〉＊0601〉＊0502〉＊050301=＊0401〉＊0201〉＊0302〉＊050101=＊0202〉＊0602〉＊0402=060401〉＊0609。结论得到了遵义汉族人HLA-DQB。等位基因频率分布的可靠资料，为我国疾病相关性研究、人类学研究提供了可靠的遗传学数据。     

HLA-DQB1基因多态性与湿热内蕴型免疫性不育症相关性研究

目的 :探讨湿热内蕴型免疫性不育症与HLA-DQB1基因多态性的关系。方法 :采用聚合酶链式反应序列特异性引物(PCR-SSP)技术,对70例抗精子抗体阳性的湿热内蕴型免疫性不育症患者和60例正常健康者的HLA-DQB1基因进行分型研究。结果 :免疫性不育症组HLA-DQB1*0601等位基因频率明显高于正常对照组(P<0.05)。结论 :HLA-DQB1*0601等位基因可能是抗精子抗体阳性的湿热内蕴型免疫性不育症的易感基因。     

人类白细胞抗原Ⅱ类基因多态性与中国人群尘螨过敏性鼻炎相关性研究

目的探索人类白细胞抗原Ⅱ类基因(human leukocyte antigenⅡ,HLA-Ⅱ)多态性在中国人群中尘螨过敏性鼻炎发病中的作用。方法选取单纯尘螨过敏性鼻炎(allergic rhinitis,AR)病人71例,健康对照92例,提取受试者外周血DNA,应用聚合酶链反应序列分型法(polymerase chain reaction sequence-based genotyping,PCR-SBT)进行HLA-Ⅱ基因(DRB1、DQB1)分型。采用R软件进行HLA-Ⅱ基因频率统计及单倍体型分析包进行统计学分析,基因频率在AR与对照组中的比较应用χ2及Fisher精确检验分析,结果进行Bonferroni多重矫正。结果共检测到16个HLA-DRB1等位基因,13个HLA-DQB1等位基因。其中DQB1*06:01:01(P校正=0.010,OR=2.347,95%CI:1.392~4.225)、DRB1*08:03:02(P校正=0.012,OR=3.213,95%CI:1.732~7.821),在尘螨过敏性病人中的基因频率较健康对照组增加,差异具有统计学意义。结果提示,HLA-DRB1*08:03:02和HLA-DQB1*06:01:01等位基因可能是中国人群尘螨过敏性鼻炎发病的风险因子。单倍体型DRB1*08:03-DQB1*06:01(19%vs 4.8%,P校正=0.007,OR=4.232,95%CI:1.822~9.237)在病例组中频率增加。结论 HLA-DRB1*08:03:02和HLA-DQB1*06:01:01等位基因可能是中国人群尘螨过敏性鼻炎发病的风险因子。     

HLA-DQB1等位基因与广西壮族人群肝癌家族聚集性的相关性

目的:探讨HLA-DQB1等位基因与广西壮族人群肝癌家族聚集性的相关性,为寻找广西壮族人群肝癌的遗传易感基因或拮抗基因提供线索。方法:采取性别、年龄±5岁配对方法,在广西壮族肝癌高发区选取肝癌高发家族成员、无癌家族成员各48例作为研究对象,采集研究对象外周血并提取全血DNA,应用PCR-SSP方法对HLA-DQB1等位基因进行检测。结果:(1)HLADQB1*02/06/07等位基因在肝癌高发家族组和无癌家族组的基因频率分别是8.33%和33.33%、33.33%和8.33%、25.00%和50.00%,差异均有统计学意义(P0.05);HLA-DQB1*04/05/08/09分别是0和8.33%、50.00%和41.67%、25.00%和16.67%、8.33%和8.33%,差异均无统计学意义(P0.05);(2)HLADQB1*02/04/05/06/07/08/09等位基因在乙型肝炎病毒感染组(HBs Ag阳性组)及非乙型肝炎病毒感染组(HBs Ag阴性组)中的基因频率分别为15.79%和22.08%、0和5.19%、42.11%和46.75%、26.32%和19.48%、47.37%和35.06%、21.05%和20.78%、5.26%和9.09%,差异均无统计学意义(P0.05)。(3)HLA-DQB1各等位基因与性别无明显相关(P0.05)。结论:(1)HLA-DQB1*02/07等位基因可能是广西壮族人群肝癌发生的拮抗基因,而HLA-DQB1*06等位基因可能为其易感基因;(2)HLA-DQB1各等位基因可能与广西壮族肝癌高发区乙肝病毒的感染及性别无明显关联。     

新疆维吾尔族HPV16感染的中晚期宫颈癌妇女HLA-DRB1及HLA-DQB1基因多态性和细胞因子相关性研究

目的探讨新疆维吾尔族妇女HPV16感染的中晚期宫颈癌HLA-DRB1和HLA-DQB1的等位基因分布及其与IFN-γ、IL-2、IL-6、IL-10的关联性。方法采集经新疆医科大学附属肿瘤医院病理科明确诊断为宫颈癌Ⅱb~Ⅳb期39例患者治疗前的血标本(宫颈癌组),同时采集居住在新疆地区健康女性50例血标本(健康对照组)。测定HLA-DRB1和HLA-DQB1基因亚组分型,并检测细胞因子IFN-γ、IL-2、IL-6、IL-10的水平。对比不同临床分期患者与健康对照组细胞因子的差异;根据患者HLA-DRB1和HLA-DQB1基因亚组分组,比较不同基因亚组间细胞因子水平的差异。结果检出HLA-DRB1等位基因8个,检出HLA-DQB1等位基因4个,其中HLA-DRB1*07、HLA-DQB1*02、HLA-DQB1*03在新疆维吾尔族HPV16感染的中晚期宫颈癌组的构成比分别为44.74%、56.41%、35.90%;健康对照组与维吾尔族HPV16感染Ⅱb和Ⅲb期宫颈癌组IFN-γ、IL-2、IL-6、IL-10水平差异均有统计学意义(P<0.05);单因素方差分析显示各HLA-DRB1、HLA-DQB1等位基因之间IFN-γ、IL-2、IL-6、IL-10水平差异均无统计学意义。结论 HLA-DRB1*07、HLA-DQB1*02、HLA-DQB1*03为新疆维吾尔族HPV16感染的中晚期宫颈癌优势表达基因;IFN-γ、IL-2、IL-6、IL-10与宫颈癌的发生、发展可能存在关联性。     

重庆地区汉族人群HLA-A、B、DRB1、DQB1等位基因多态性的研究

目的 研究重庆地区人群HLA-A、B、DRB1和DQB1位点等位基因的多态性特点.方法 采用序列特异性引物聚合酶链反应(PCR-SSP)技术对1 664名重庆籍健康人进行HLA-A、B、DRB1、DQB1等位基因的低分辨分型,并与国内其他地区汉族人群进行比较.结果 本次研究共检出HLA-A、B、DRB1、DQB1位点等位基因62种,其中A位点14种,B位点27种,DRB1位点13种,DQB1位点8种.A位点中A*11(34.62%)、A*02(28.81%)、A*24(14.93%)、A*30(5.53%)为重庆人群的优势基因.B位点中B*46(14.92%)＞B*40(12.96%)＞B*13(12.39%)＞B*51(7.26%).DRB1位点中,频率最高的为DRB1*09(15.65%),其次为DRB1*12(14.78%)、DRB1*14(14.49%)、DRB1*04(14.49%).DQB1位点中,频率最高的为DQB1*07(26.04%),其次为DQB1*05(19.94%)、DQB1*09(15.51%).与其他地区不同人群相比,HLA-A、B、DRB1、DQB1各位点等住基因的分布均有显著的差异.结论 重庆地区人群的HLA-A、B、DRB1、DQB1位点等住基因符合南方汉族人群分布特点,具有复杂的多态性,中国各地常见的基因均有分布,白血病及其他器官移植患者在重庆不难找到合适的供者.     

山东地区MG易感性与HLA—DQB1基因多态性的相关性研究

目的 探讨中国北方汉人HLA－DQB1基因和重症肌无力的遗传易性感笥的相关性。方法 运用PCR－SSP基因分型方法,对53例MG患者及50例健康对照组HLA－DQB1基因进行分型,并对患者组和健康对照组的DQB1各等位基因频率进行比较。结果 DQB1＊0303的频率在患者组中明显升高,差异具有显著性意义。结论 DQB1＊0303参与北方汉人MG的易感性。     

中国湖北汉族人群HLA-DRB1基因多态性研究

目的:调查湖北汉族人群人类白细胞抗原(HLA)-DRB1基因多态性,获得完整准确的遗传学数据。方法:应用序列特异性引物聚合酶链反应(PCR-SSP)方法对213名随机选取无亲缘关系的湖北籍汉族健康体检者或健康献血员进行HLA-PDRB1基因型检测。结果:在213名正常个体中,发现基因频率(GF)较高的有DRB1*1501-1502(GF=11.0%)、*1101-1105(GF=8.5%)、*0901(GF=6.8%)、*1301-1302(GF=6.6%)、DRB4*0101(GF=19.0%)、DRB5*0101(GF=16.9%),低频率等位基因是DRB1*04、*1001和*0101-0103。结论:从基因水平分析了HLA-DRB1基因在湖北汉族群体中的分布特征,提供了一套比较完整准确的DRB1基因频率,为人类学和疾病相关性等研究提供了重要的参考数据。     

HLA-DQA1, -DQB1 polymorphism distribution in Chinese women with pregnancy induced hypertension in Shanghai area.

OBJECTIVE: To explore the association of human leukocyte antigen (HLA) with pregnancy induced hypertension (PIH). METHODS: We oligotyped HLA-DQA1, -DQB1 locus of 30 Chinese PIH families and 14 control families in Shanghai area by polymerase chain reaction-sequence specific oligonucleotide (PCR-SSO) hybridization method (probes labeled by nonradioactive technique). RESULTS: Compared with the control group, the allelic frequency of HLA-DQB1 * 0502 was significantly higher in PIH couples, and the sharing of HLA-DQA1 increased in PIH couples as well. No difference was found in HLA-DQA1 allelic frequencies or HLA-DQB1 sharing between the two groups. Analysis of neither HLA-DQA1 nor HLA-DQB1 allelic frequencies in PIH patients and PIH mother-and-fetuses showed positive result. CONCLUSION: HLA-DQB1 * 0502 may be a marker of susceptibility to PIH. DQB1 * 0502 itself or some gene(s) located in HLA class II region and in linkage disequilibrium with 0502 affect maternal T cell immunity during pregnancy. The increase of compatibility in HLA-D region causes the production of blocking antibody to decrease.     

宫颈癌与HLA等位基因DQB1*03、DR15的相关性研究

目的: 探讨我国陕西地区宫颈癌的发生与人类白细胞抗原(HLA)-DQB1*03、DR15等位基因的相关性.方法: 采用序列特异性引物的聚合酶链式反应(PCR-SSP)方法,扩增HLA等位基因DQB1*03、DR15的目的DNA片段(分别为79、197 bp),分析两对等位基因在陕西地区宫颈癌患者和正常人中分布频率的差异.结果: 45名宫颈癌患者组中DQB1*03等位基因频率显著高于50名健康对照组,DR15等位基因频率在两组中的分布无显著差异.结论: HLA等位基因DQB1*03可能与宫颈癌的发生具有相关性,DR15可能与宫颈癌的发生不存在关联.     

Association of HLA-DQB1 coding region with unexplained recurrent spontaneous abortion

Background DNA analysis has shown a lack of significant compatibility between couples affected by unexplained recurrent spontaneous abortion (URSA) compared with normal fertile couples,^8 although one study that made use of a PCR-sequence-specific oligonucleotide (SSO) method did observe evidence of significant compatibility in the HLA-DQA1 and DQB1 alleles between patients and aborted fetuses.^9 This study was designed to investigate whether URSA were associated with particular DQ alleles or promoter alleles.Methods Thirty-two patients with URSA and 54 women who had had at least one successful pregnancy were included in this study. HLA-DQ genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The HLA-DQB1 promoter was detected by the SSO and sequence-specific primer (SSP) methods. The DQA1, DQB1, and DQB1 promoter (QBP) gene frequencies in the patients were compared with the gene frequencies in normal controls. The data were analyzed statistically with the x^2 and Fisher‘s exact tests.Results The results showed that the frequency of DQB1 ^*0604/0605 was significantly higher and the frequency of DQB1^* 0501/0502 was significantly lower in the patient group as compared with the normal controls. In addition, the frequencies of the DQA1 ^* 01-DQB1 ^* 0604/0605 and QBP6.2-DQB1 ^* 0604/0605 haplotypes were overrepresented in the patients relative to the controls. Our results did not show any differences between URSA patients and the controls with regard to DQA1 and QBP allele frequencies.Conclusions Our data suggest that URSA is associated with the HLA-DQB1 coding region, and is not associated with its upstream regulatory region. The DQB1 ^* 0604/0605, DQA1 ^* 01-DQB1 ^* 0604/0605, and QBP6.2-DQBI^* 0604/0605 haplotypes may confer susceptibility to URSA, while the DQB1 ^* 0501/0502 allele may protect women from URSA.     

Contribution of the absence of aspartic acid at position 57 of the HLA-DQ beta chain to predisposition to insulin-dependent diabetes mellitus in a southern Chinese population

OBJECTIVE To investigate the association of the absence or presence of aspartic acid at position 57 of the HLA-DQ beta chain (NA or A) with susceptibility or resistance to insulin-dependent diabetes mellitus (IDDM) in a Southern Chinese population.

METHODS Sixty-nine IDDM patients and 47 healthy controls in a Southern Chinese population were HLA-DQB1 genotyped by one-step sequence specific polymerase chain reaction (ssPCR).

RESULTS The frequencies of NA and A were 64.5% and 35.5% in the IDDM patients, and 40.4% and 59.6% in the control subjects respectively (RR for NA was 2.68, P < 0.01). The frequencies of NA/NA, NA/A and A/A phenotypes were 47.8%, 33.3% and 18.8% in the IDDM patients, and 31.9%, 17.0% and 51.1% in the controls respectively (P < 0.01). The frequency of A/A phenotype was significantly lower in the IDDM patients than in the control subjects (RR = 0.22, P < 0.01). DQB1* 0302 and DQB1* 0201 were more frequent in IDDM patients than in control subjects. The younger the age of IDDM onset, the higher the allele frequencies of DQB1* 0201 and DQB1* 0302.

CONCLUSIONS The present study suggests that the NA confers the susceptibility to IDDM, while the A confers the protection against IDDM in patients of Southern Chinese origin. These associations are more clearcut in childhood-onset IDDM patients.

     

Contribution of the absence of aspartic acid at position 57 of the HLA-DQ β chain to predisposition to insulin-dependent diabetes mellitus in a Southern Chinese population

Objective To investigate the association of the absence or presence of aspartic acid at position 57 of the HLA-DQ β chain (NA or A) with susceptibility or resistance to insulin-dependent diabetes mellitus (IDDM) in a Southern Chinese population.Methods Sixty-nine IDDM patients and 47 healthy controls in a Southern Chinese population were HLA-DQB1 genotyped by one-step sequence specific polymerase chain reaction (ssPCR).Results The frequencies of NA and A were 64.5% and 35.5% in the IDDM patients, and 40.4% and 59.6% in the control subjects respectively (RR for NA was 2.68, P<0.01). The frequencies of NA/NA, NA/A and A/A phenotypes were 47.8%, 33.3% and 18.8% in the IDDM patients, and 31.9%, 17.0% and 51.1% in the controls respectively (P<0.01). The frequency of A/A phenotype was significantly lower in the IDDM patients than in the control subjects (RR=0.22, P<0.01). DQB1* 0302 and DQB1* 0201 were more frequent in IDDM patients than in control subjects. The younger the age of IDDM onset, the higher the allele frequencies of DQB1* 0201 and DQB1* 0302.Conclusion The present study suggests that the NA confers the susceptibility to IDDM, while the A confers the protection against IDDM in patients of Southern Chinese origin. These associations are more clearcut in childhood-onset IDDM patients.     

HLA-DR和HLA-DQ基因型和单倍型在深圳地区结核病发病机制中的作用

目的探讨HLA-DR和HLA-DQ单倍型在深圳地区结核病发病机制中的作用及机制。方法采用PCR-SSP技术对146例深圳地区肺结核患者及146例健康志愿者的HLA-DR的31个等位基因和HLA-DQ基因的8个等位基因行分型,比较两组间各等位基因频率(GF)和单倍型频率(HF)并计算其优势比(OR)。结果肺结核组DRB1*1601-1605/1607-1608、DRB1*040101-44位点的基因频率显著高于对照组(P均<0.05),其GF比和OR分别为14.39%vs8.59%、19.33%vs10.86%、1.85vs2.08;DR4-DRB4和DR16-DRB5单倍型频率在两组人群间有显著差异,肺结核组明显高于对照组(P均<0.05),其OR分别为2.35,2.97。结论DR4-DRB4和DR16-DRB5单倍型频率在两组人群间的显著差异可能分别是由DRB1*040101-44(DR4)和DRB1*1601-1605/1607-1608(DR16)在两组间的显著差异造成,后两者可能是深圳地区结核病发病的易感基因。     

HLA-DR和 HLA-DQ等位基因与口腔扁平苔藓的相关性

目的研究上海及江浙地区汉族人群人类白细胞抗原(HLA)-DRB1、HLA-DQB1等位基因与口腔扁平苔藓(OLP)发病的关系。方法采用聚合酶链式反应-序列特异性引物(PCR-SSP)法,检测上海及江浙地区44例OLP患者和150例正常对照者的HLA-DRB1、HLA-DQB1等位基因表现频率,所得数据在OLP与正常对照之间以及不同类型OLP患者之间进行比较分析。结果与正常对照组相比,OLP组HLA-DRB1*09和HLA-DRB1*07基因表现频率均明显增高,分别为56.8%vs31.3%(P<0.01)和27.3%vs13.3%(P<0.05);而HLA-DQB1*06基因表现频率则显著降低(18.8%vs42.5%)(P<0.01)。OLP组内比较显示,HLA-DRB1*04表达频率在具有糜烂表现的OLP患者中显著升高,与白纹组相比具有显著性差异(P<0.05)。结论HLA-DRB1*09、DRB1*07等位基因与上海及江浙地区部分人群的OLP易感性相关;HLA-DQB1*06等位基因可能与OLP的抵抗性相关联;HLA-DRB1*04可能与糜烂型OLP的发生有关。