HLA-DQB1等位基因多态性及Th1/Th2细胞相关因子与广西瑶族肝癌家族聚集性的相关性

目的：探讨HLA-DQB1等位基因多态性及相应位点下Th1/Th2细胞相关因子IL-2、IL-4及IL-10对广西瑶族原发性肝癌家族聚集性的影响,为寻找广西瑶族原发性肝癌的遗传易感基因或拮抗基因提供线索。方法：在广西肝癌高发区选取民族为瑶族的肝癌高发家族成员、无癌家族成员各40例作为研究对象（采用相同性别、年龄±5岁配对方法）,采集研究对象外周血并提取全血DNA,应用PCR-SSP的方法对HLA-DQB1等位基因进行检测,应用ELISA法检测IL-2、IL-4、IL-10的水平。结果：（1）广西瑶族肝癌高发家族组的HLA-DQB1*02/09等位基因表达频率高于无癌家族组,两组比较差异明显,具有统计学意义（P<0.05）;而两组间的HLA-DQB1*04/05/06/07/08等位基因表达频率无显著性差异（P>0.05）。（2）HLA-DQB1各等位基因在乙型肝炎病毒感染组（HBsAg阳性组）及非乙型肝炎病毒感染组（HBsAg阴性组）间的分布频率比较无显著性差异（P值均>0.05）。（3）广西瑶族肝癌高发家族成员组中Th2细胞相关因子IL-4、IL-10平均表达水平高于无癌家族成员组,差异具有统计学意义（P<0.05）,而两组间的IL-2浓度无显著性差异（P>0.05）。（4）两组中HLA-DQB1*02阳性成员的IL-10平均表达水平高于HLA-DQB1*02阴性成员,差异具有统计学意义（P<0.05）。（5）两组中HLA-DQB1*09阳性成员的IL-4平均表达水平高于HLA-DQB1*09阴性成员,差异具有统计学意义（P<0.05）。结论：（1）HLA-DQB1*02/09等位基因可能是广西瑶族居民原发性肝癌发生的易感基因。（2）HLA-DQB1各等位基因与广西瑶族居民的HBV感染可能无显著相关性。（3）IL-4、IL-10表达水平失衡可能是广西瑶族肝癌家族聚集性的危险因素。（4）IL-10表达水平失衡可能与HLA-DQB1*02等位基因的携带有关,而IL-4表达水平失衡可能与HLA-DQB1*09等位基因的携带有关,它们之间共同作用可能与广西瑶族肝癌家族聚集性的发生有相关性。     

喀什维吾尔族宫颈癌患者HPV16型感染及其人类白细胞抗原-DQB1基因多态性的关系

目的 探讨HPV16型病毒感染与宿主人类白细胞抗原HLA-DQB1基因多态性和喀什维吾尔族宫颈癌发生的相关性.方法 采用导流杂交基因芯片技术及聚合酶联反应序列特异性寡核苷酸探针(Polymerase chain reaction sequence-specific oligonucleotide ,PCR-SSO)法检测111例喀什维吾尔族宫颈癌患者、100例正常妇女宫颈组织HPV感染及型别分布和HLA-DQB1的等位基因.结果 (1)111例宫颈癌患者中,HPV总感染率81.9%(91/111),其中HPV16型感染占的比例最高,为91.2%(83/91),100例正常宫颈组织中HPV阳性者为9例,阳性率为9.00%(9/100),其中HPV16阳性2例,两组之间差异有显著性(P<0.01).(2)HLA-DQB1·03在宫颈癌组中出现的频率明显低于对照组,两组之间差异有统计学意义(χ2=4,P=0,OR=0.607,95% CI=1.042～2.478).HLA-DQB1·06在宫颈癌组中出现的频率明显高于对照组,两组之间差异有统计学意义(χ2=7.112、P=0,OR=2,95% CI=1.204～3.549).宫颈癌中HLA-DQB1·06阳性者HPV16的感染率明显高于阴性者(χ2=4.907,P=0.027,OR=2,95% CI=1.092～6.840),两组比较差异有统计学意义,说明携带HLA-DQB1·06等位基因的维吾尔族妇女更容易被HPV16感染.HLA-DQB1的其他等位基因在宫颈癌组及对照组中出现的频率差异无显著性(P>0.05).结论 HLA-DQB1·03可能为维吾尔族妇女宫颈癌的保护基因,而HLA-DQB1·06可能与维吾尔族妇女对宫颈癌的遗传易感性有关,是维吾尔族妇女对宫颈癌的易感基因,HLA-DQB1·06基因型可能增加了HPV16 阳性妇女患宫颈癌的危险性,可能是维吾尔族妇女宫颈癌患病率高的原因之一.维吾尔族妇女宫颈癌易感基因及保护基因的检测可能在高危人群的检测及群体遗传干预工作中有一定的指导意义.     

人白细胞抗原(HLA)-DRB1 *0901、1501和HLA-DQB1 *0301、0602与新疆哈萨克族食管鳞状细胞癌相关性

目的 从基因水平探讨新疆哈萨克族食管鳞状细胞癌HLA-DRB1和DQB1等位基因的遗传易感性,为寻找哈萨克族食管鳞状细胞癌的易感基因提供线索.方法 运用序列特异性引物聚合酶链反应(PCR-SSP)技术,检测新疆哈萨克族食管鳞状细胞癌200例、正常食管黏膜177例HLA-DRB1 *0901、1501和DQB1 *0301、0602等位基因的分布.结果 新疆哈萨克族食管鳞状细胞癌患者HLA-DRB1 *1501、DQB1 *0301和DQB1 *0602基因分布频率(0.455,0.760和0.690)明显高于177例正常食管黏膜上述等位基因分布频率(0.232,0.520,0.554),差异具有统计学意义(OR=2.78,2.93,1.80;P值均<0.05);新疆哈萨克族食管鳞状细胞癌HLA-DRB1 *0901等位基因分布频率(0.105)与哈萨克族正常食管黏膜(0.102)对比,差异无统计学意义(OR=11036,P>0.05);HLA-DQB1 *0602等位基因的分布频率在哈萨克族中低分化鳞状细胞癌组中的分布频率(0.742)高于高分化鳞状细胞癌组(0.597),差异具有统计学意义(P<0.05).结论 HLA-DRB1 *1501、DQB1 *0301和DQB1 *0602可能是哈萨克族食管鳞状细胞癌的易感基因,HLA-DQB1 *0602与哈萨克族食管鳞状细胞癌的分化程度有关.     

新疆地区汉族和维吾尔族部分人群HLA-DRB1、HLA-DQB1、HLA-DPB1基因多态性与单倍型的比较

目的了解中国新疆维吾尔自治区汉族和维吾尔族人类白细胞抗原DRB1(HLA-DRB1)、HLA-DQB1、HLA-DPB1高分辨分型基础上的基因多态性和单倍型分布的特点。方法应用聚合酶链反应-直接测序基因分型(PCR-SBT)法对新疆地区188例汉族人群与90例维吾尔族人群进行HLA-DRB1、HLA-DQB1、HLA-DPB1基因分型,直接计数法计算基因频率,应用Arlequin3.5软件以最大似然法获得单倍型频率。结果汉族人群频率最高的HLA-Ⅱ类基因分别是DRB1*09∶01(12.8%)、DQB1*03∶01(20.3%)和DPB1*05∶01(33.5%);三位点组成的单倍型频率最高的分别是DRB1*09∶01-DQB1*03∶03(8.8%)、DRB1*09∶01-DPB1*05∶01(5.0%)、DQB1*03∶01-DPB1*05∶01(9.6%)和DRB1*09∶01-DQB1*03∶03-DPB1*05∶01(6.3%)。维吾尔族人群频率最高的HLA-Ⅱ类基因分别是DRB1*07∶01(18.3%)、DQB1*03∶01(18.9%)和DPB1*04∶01(30.0%);三位点组成的单倍型频率最高的分别是DRB1*07∶01-DQB1*02∶02(16.1%)、DRB1*07∶01-DPB1*04∶01(5.0%)、DQB1*03∶01-DPB1*04∶01(7.3%)、DRB1*07∶01-DQB1*02∶02-DPB1*04∶01(7.4%)。两组人群中等位基因有显著差异的是∶DRB1*04∶04、DRB1*07∶01、DRB1*08∶03、DRB1*11∶04、DRB1*12∶02、DRB1*13∶01、DRB1*15∶01、DQB1*02∶02、DQB1*06∶01、DPB1*04∶01和DPB1*05∶01。结论中国新疆汉族与维吾尔族人群HLA-DRB1、HLA-DQB1、HLA-DPB1等位基因频率、单倍型频率分布均有自己的多态性特征。     

山西汉族原发性干燥综合征与HLA-DQ基因多态性相关性的研究

目的:探讨山西汉族人群原发性干燥综合征(pSS)与HLA-DQ等位基因的相关性,从基因水平上探索pSS的发病机制。方法:应用聚合酶链反应-序列特异性引物(PCR-SSP)法对pSS患者与健康对照进行HLA-DQA1、HLA-DQB1基因的分型;采用χ2检验和Fisher’s精确检验比较两组各等位基因频率的差异。结果:(1)在100例山西汉族健康人及pSS患者中,HLA-DQA1*0501基因频率分别为12.0%和22.0%。与健康对照相比较,pSS患者中HLA-DQA1*0501基因频率显著增高(χ2=7.087,P<0.05,RR=2.068)。(2)pSS患者HLA-DQA1*0301/2等位基因频率为13.0%,显著低于健康对照组的24.5%(χ2=8.681,P<0.05,RR=0.460)。(3)pSS患者中HLA-DQB1*0201基因频率为28.5%,显著高于健康人的18.5%(χ2=5.563,P<0.05,RR=1.756)。结论:HLA-DQA1*0501和HLA-DQB1*0201等位基因可能是山西汉族pSS的易感基因,而HLA-DQA1*0301/2等位基因可能是其保护基因。     

HLA-DRB1*04等位基因多态性与乙型肝炎病毒感染结局关联分析

目的从分子遗传学角度探讨乙型肝炎病毒(hepatitis B virus,HBV)感染结局与HLA-DRB1*04等位基因的相关性。方法采用聚合酶链反应-序列特异性引物(polymerase chain reaction-seque nce specific primers,PCR-SSP)技术检测HLA-DRB1*04等位基因,并比较106例无症状HBV携带者(HBV携带组),93例慢性乙型肝炎患者、77例乙肝肝硬化者、102例HBV感染后自然恢复者(对照组)HLA-DRB1*04等位基因频率及HBV不同复制状态下HLA-DRB1*04等位基因频率。结果HBV携带组、慢性乙肝组、乙肝肝硬化组HLA-DRB1*04等位基因频率高于对照组(分别为25.94%、26.34%、27.92%和14.22%,P<0.01);HLA-DRB1*0401基因频率高于对照组(分别为20.91%、24.49%、22.09%和8.62%,P均<0.05);HLA-DRB1*0405基因频率较对照组低(3.64%、2.04%、3.49%和15.52%,P<0.01、0.01、0.05)。各病例组之间HLA-DRB1*04等位基因频率差异无统计学意义(P>0.05)。HBV不同复制状态HLA-DRB1*04等位基因频率差异无统计学意义(P>0.05)。结论HLA-DRB1*04是决定HBV感染结局的因素之一,但不影响HBV在体内复制。     

HLA-DRB1等位基因与吉林地区汉族乙肝疫苗免疫应答的关联研究

目的:探讨HLA-DRB1等位基因与吉林地区汉族乙肝疫苗免疫应答的关联性。方法:采用聚合酶链反应-序列特异性引物(PCR-SSP)分型技术,对84例乙肝疫苗无或低应答者HLA-DRB1等位基因进行检测,与78例乙肝疫苗中或强应答者人群进行对照。结果:①HLA-DRB1*14等位基因频率在无或低应答组为23.8%,中或强应答组为5.13%,两组之间比较有统计学差异(P<0.05);②HLA-DRB1*12、HLA-DRB1*15等位基因频率分别在无或低应答组为4.76%和7.14%,在中或强应答组为23.1%和24.4%,两组之间比较也存在统计学差异(P<0.05)。③等位基因HLA-DRB1*07(2.38%和5.12%),HLA-DRB1*08(9.52%和8.97%),HLA-DRB1*09(7.14%和10.3%),HLA-DRB1*11(7.14%和7.69%),HLA-DRB1*13(4.76%和6.41%)及HLA-DRB1*16(4.76%和5.13%),在无或低应答组和在中或强应答组之间基因频率分布没有统计学差异(P>0.05)。结论:吉林地区汉族乙肝疫苗接种后,①HLA-DRB1*14等位基因可能与无或低应答相关;②HLA-DRB1*12、15等位基因可能与中或强应答相关;③未检测到HLA-DRB1*07、08、09、11、13、16等位基因与免疫应答水平之间有明显的相关性。     

Grave 病与 HLA-DQA1 和 HLA-DQB1等位基因多态性的相关性分析

目的 探索Grave病(Graves'disease,GD)与HLA-DQA1和HLA-DQB1等位基因多态性之间关系.方法 选取就诊于我院的Grave病患者为研究对象.使用PCR-SBT方法对Grave病患者及正常对照组进行测序分析,使用SPSS 19.0统计软件进行分析GD患者组与对照组间差异性.结果 GD患者的HLA-DQAl* 01:01、*01:03、* 03:03、* 05:03的频率显著高于对照组,HLA-DQA1* 02:01、*05:05的基因频率明显低于正常对照组,P均＜0.05,差异具有统计学意义.HLA-DQB1* 04:01、*06:01的频率显著高于对照组,HLA-DQB1 * 02:02、*05:01的基因频率明显低于正常对照组,P均＜0.05,差异具有统计学意义.结论 HLA-DQAl* 01:01、* 01:03、* 03:03、* 05:03和 HLA-DQB1 * 04:01、* 06:01 可能为 GD的危险因素.HLA-DQA1* 02:01、*05:05和 HLA-DQB1 * 02:02、* 05:01 可能为 GD 的保护因素.     

焦虑对体液免疫功能影响及其与HLA-DQB1等位基因的关系

目的:研究焦虑对体液免疫功能的影响及其与HLA-DQB1等位基因多态性的关系.方法:随机挑选某医院健康体检住院医生31名,选用状态-特质焦虑量表(STAI)来测量其焦虑状况,实验室检测IgG、IgA、IgM以及补体C3、C4水平,并利用PCR扩增各研究对象HLA-DQB1*02、*03、*04、*05和*06五个位点基因多态性.结果:状态焦虑 (Ta)和特质焦虑 (Tc)均同补体C3呈正相关,有统计学意义.HLA-DQB1*02位点阳性和阴性的个体状态焦虑的差异有统计学意义(P＜0.05),而补体C3的差异不具有统计学意义(P＞0.05).HLA-DQB1* 04位点阳性和阴性的个体状态焦虑和特质焦虑的差异都有统计学意义(P＜0.05),而补体C3的差异不具有统计学意义(P＜0.05).结论:焦虑可以引起某些体液免疫功能指标的改变并与HLA-DQB1等位基因表型有关.     

HLA-DQB1基因多态性与新疆维吾尔族人群结核病易感性的相关性研究

目的:探讨人类白细胞抗原(HLA)-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:采用病例一对照的研究方法,应用聚合酶链反应一序列特异性引物(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-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:肺结核病例组中HLA-DQB1*0201基因频率显著高于健康对照组,两组的GF分别为40.13%、19.15%,差异有统计学意义(P<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,两组的GF分别为6.16%、10.27%,但P值经过校正后无显著性差异(P0.05).结论:HLA-DQB1*0201等位基因与新疆维吾尔族人群结核病强相关,DQB1*0201可能是其易感基因.     

Human leukocyte antigen-DRB1*1501 and DQB1*0602 alleles are cervical cancer protective factors among Uighur and Han people in Xinjiang,China

Human papillomavirus (HPV) infection is a major risk factor for cervical cancer. However, only some high risk human papillomavirus (HR-HPV)-infected women progress to cervical cancer, host immunogenetic factors human leukocyte antigen (HLA) may account for viral antigens presenting individually or together in the progression to cervical cancer. This study examined the association between the development of invasive cervical cancer (ICC) and the determinant factors including HLA-DRB1*1501 and DQB1*0602, HR-HPV infection among Chinese Uighur and Han populations. Blood samples, cervical swabs and biopsies were obtained from 287 patients with ICC (192 Uighurs and 95 Hans) and 312 healthy controls (218 Uighurs and 94 Hans). HPV DNA was detected by PCR and HLA-DRB1*1501 and DQB1*0602 alleles were performed using PCR-SSP method. HPV16 infection rates was significantly higher among Uighur and Han with ICC as compared to healthy controls (OR = 58.317; 95% CI: 39.663-85.744; OR = 33.778; 95% CI: 12.581-90.691; P < 0.05 for all). HLA-DRB1*1501 (OR = 0.305; 95% CI: 0.115-0.813; P < 0.05) and HLA-DRB1*1501-DQB1*0602 haplotype frequencies (OR = 0.274; 95% CI: 0.086-0.874; P < 0.05) were significantly reduced in Han ICC. The HLA-DQB1*0602 frequency significantly decreased among Uighur women with ICC (OR = 0.482; 95% CI: 0.325-0.716; P < 0.05). Similar tendencies were observed for DQB1*0602 with HPV16-positive ICC (OR = 0.550; 95% CI: 0.362-0.837; P < 0.05). This study suggests that HLA-DRB1*1501 and DQB1*0602 alleles may influence the immune response to HPV16 infection and decrease the risk of ICC among Uighurs and Hans in Xinjiang, China.     

HLA class-I and class-II allele frequencies and two-locus haplotypes in Melanesians of Vanuatu and New Caledonia

HLA class-I and class-II allele frequencies and two-locus haplotypes were examined in 367 unrelated Melanesians living on the islands of Vanuatu and New Caledonia. Diversity at all HLA class-I and class-II loci was relatively limited. In class-I loci, three HLA-A allelic groups (HLA-A*24, HLA-A*34 and HLA-A*11), seven HLA-B alleles or allelic groups (HLA-B*1506, HLA-B*5602, HLA-B*13, HLA-B*5601, HLA-B*4001, HLA-B*4002 and HLA-B*2704) and four HLA-C alleles or allelic groups (HLA-Cw*04, HLA-Cw*01, HLA-Cw*0702 and HLA-Cw*15) constituted more than 90% of the alleles observed. In the class-II loci, four HLA-DRB1 alleles (HLA-DRB1*15, HLA-DRB1*11, HLA-DRB1*04 and HLA-DRB1*16), three HLA-DRB3-5 alleles (HLA-DRB3*02, HLA-DRB4*01 and HLA-DRB5*01/02) and five HLA-DQB1 alleles (HLA-DQB1*0301, HLA-DQB1*04, HLA-DQB1*05, HLA-DQB1*0601 and HLA-DQB1*0602) constituted over 93, 97 and 98% of the alleles observed, respectively. Homozygosity showed significant departures from expected levels for neutrality based on allele frequency (i.e. excess diversity) at the HLA-B, HLA-Cw, HLA-DQB1 and HLA-DRB3/5 loci on some islands. The locus with the strongest departure from neutrality was HLA-DQB1, homozygosity being significantly lower than expected on all islands except New Caledonia. No consistent pattern was demonstrated for any HLA locus in relation to malaria endemicity.     

HLA-DRB1*1602 allele is positively associated with HPV cervical infection in Bolivian Andean women

Incidence of cervical cancer is high among Bolivian Andean women. Human papillomavirus (HPV) infection is known as the major risk factor of cervical cancer. The host immune system plays an important role in the outcome of HPV infection and associated malignancies. In order to study the immunogenetic background of Bolivian Andean women with regard to HPV infection status, we compared HLA class I and class II allele frequencies between 37 HPV positive and 68 HPV negative Bolivian women. Demographic variables, including distribution of Andean ethnicities, were similar in both groups. Comparison of HLA class I allele frequencies between both groups indicated no significant difference. In contrast, HLA class II DRB1*1602 allele, an Amerindian allele, was significantly higher in the HPV positive women compared with HPV negative controls (chi(2) = 5.2, p < 0.05, odds ratio = 3.17; 95% confidence interval = 1.4-8.8). HPV types present in the HPV positive group were HPV-18, -16, -31, -33, and -58. These results suggest that HLA class II DRB1*1602 may confer susceptibility to infection with genetically related HPV types. This is the first report of an HLA class II association with HPV infection in an Andean population.     

Protective association of HLA-DRB1*13:02, HLA-DRB1*04:06, and HLA-DQB1*06:04 alleles with cervical cancer in a Korean population

Human leukocyte antigen (HLA) class II alleles have been previously associated with cervical cancer. However, these associations vary widely across racial and ethnic groups. Therefore, we evaluated the effect of HLA class II alleles on cervical cancer in a Korean population. HLA-DRB1, HLA-DQB1, and HLA-DQA1 alleles were analyzed in 457 cervical cancer patients and compared to those of 926 control subjects. The odds ratio (OR) of each allele between the patients and controls was calculated using the logistic regression model. Patients, had significantly lower frequencies of HLA-DRB1 and HLA-DQB1 alleles than control subjects: HLA-DRB1*13:02:01 (4.4% vs 8.8%; OR 0.48, 95% confidence interval (CI) 0.27–0.84; p = 0.001), HLA-DRB1*04:06 (2.1% vs 4.7%; OR 0.44, 95% CI 0.20–0.97; p = 0.033), and HLA-DQB1*06:04:01 (2.3% vs 5.0%; OR 0.46, 95% CI 0.22–0.94; p = 0.021). No significant association was observed for HLA-DQA1. Protective associations between HLA-DRB1*13:02, HLA-DRB1*04:06, and HLA-DQB1*06:04 alleles and cervical cancer were found in the Korean population     

南疆维吾尔族妇女宫颈癌与HPV感染及HLA-DRB1基因多态性的关系研究

目的 探讨人乳头状瘤病毒(human papilloma virus,HPV)感染及人类白细胞抗原(HLA)-DRB1基因多态性与南疆维吾尔族宫颈癌的关系.方法 采用导流杂交基因芯片技术及聚合酶链反应序列特异性寡核苷酸探针(polymerase chain reaction sequence-specific oligonucleotide,PCRSSO)法对200例南疆维吾尔族宫颈癌患者及200例正常妇女的宫颈组织检测HPV的21种型别(包括13种高危型:16,18,31,33,35,39,45,51,52,56,58,59,68;5种低危型:6,11,42,43,44;3种中国人群常见型:53,66,CP8304型)及HLA-DRB1的13个等位基因.结果 (1)200例官颈癌组织中HPV阳性者共177例(包括单一感染及多重感染),阳性率为88.5%;200例对照组中HPV阳性的标本为14例,阳性率为7.0%.HPV16在HPV阳性的宫颈癌中占的比例最高,其出现的频率为90.96%,其次为HPV18(5.08%)、HPV68(3.95%)、HPV45(3.39%)、HPV58(3.39%)、HPV39(1.69%)、HPV31(1.69%)、HPV56(1.13%)等.比较两组HPV总感染率及HPV16的阳性率,宫颈癌组明显高于对照组,两者差异有统计学意义(P＜0.0001).(2)官颈癌中HLA-DRB1*15阳性者HPV16的感染率高于阴性者,差异有统计学意义,说明携带HLA-DRB1*15等位基因的妇女更容易被HPV16感染.官颈癌中HLA-DRB1*12阳性者中HPV16的阳性率明显低于HLA-DRB1*12阴性者,说明HLA-DRB1*12对HPV16感染有保护作用.结论 南疆维吾尔族宫颈癌患者及正常人群中以HPV16感染为主,比例很高;其次为HPV18、HPV68,HPV68在第3位与文献报道不同,可能是南疆维吾尔族较易感染的类型.HLA-DRB1*15可能与维吾尔族妇女对官颈癌的遗传易感性及对HPV16感染易感性有关;HLA-DRB1*12为HPV16感染的保护基因.维吾尔族妇女官颈癌易感基因及保护基因的检测在宫颈癌高危人群的检测及群体遗传干预工作中有一定的指导意义.

Abstract：

Objective To investigate the relationships between the HPV infection and race susceptibility in the carcinogenesis of Uighur women with cervical cancer from the southern Xinjiang, one of the high risk region of cervical cancer in China. Methods To detect 21 subtypes of HPV and the 13 alleles of HLA from 200 cervical cancer cases and 200 normal tissues, by using flow-through hybridization and gene chip (HybriMax) method and polymerase chain reaction sequence-specific oligonucleotide method (PCRSSO). Results ( 1 )The proportion of HPV positive in cervical cancer and control group were 88.5% and 7.0% respecfively;HPV16 was the most common type in HPV positive cervical cancer patients with the rate of 90.96%, following were HPV18 (5.08%), HPV68(3.95% ),HPV45 (3.39%), HPV58 (3.39%),HPV39( 1.69% ), HPV31 ( 1.69% ), HPV56( 1.13% ). In cervical cancer and control group, the positive rate of HPV and HPV16 were significantly higher than that in control group. (2) In cervical cancer group the frequency of HLA-DRB1 * 15 in HPV positive cervical cancer cases was significantly higher than that among the HPV negative cases. While the frequency of HLA-DRB1 * 12 in HPV positive eervical caneer eases was significantly lower than that in the HPV negative e asea. Conclusion HPV16 was the most common type in both cervical cancer and control groups, the frequency of HPV16 in cervical carcinomas was very high, following HPV18 and HPV68, and HPV68 ranked third which was different from the results of other reports,this indicates that Uighur women are infected with this type more common. It appears that HLA-DRB1 * 15may be related to the susceptibility to cervical cancer and the HPV16 infection among the Uighur women,while the HLA-DRB1 * 12 the protective gene to HPV16 infection in Uighur women. The study of HLA alleles in the carcinogenesis of cervical carcinomas may play an important role in the gene intervention research of cervical cancer.     

Human leukocyte antigen class II alleles and risk of cervical cancer in China

Human leukocyte antigen (HLA) class II alleles have been associated with an increased or decreased risk of developing cervical cancer through infection with oncogenic forms of human papillomavirus (HPV). To verify whether HLA class II allelic polymorphism is related to cervical cancer in China, 133 cervical cancers and 98 healthy controls were analyzed for HLA typing. Our results showed that DPB1*1301 allele frequency was significantly higher in the cervical cancers compared with healthy controls (OR, 3.793; p = 0.002; Pc = 0.04). A significant relationship was found between DRB1*150101-DQB1*0602 haplotype (OR, 0.180; p < 0.0001; Pc < 0.003), DRB1*070101-DQB1*0201 haplotype (OR, 0.110; p = 0.001; Pc = 0.03), and decreased risk for cervical cancer. Similar tendencies were observed for DRB1*150101-DQB1*0602 haplotype with HPV16 positive cervical cancers (OR, 0.182; p = 0.001; Pc = 0.021), and for DRB1*070101-DQB1*0201 haplotype (OR, 0.144; p =0.003; Pc = 0.063). These results indicate that HLA-DPB1*1301 may confer susceptibility to cervical cancer, and the haplotypes DRB1*150101-DQB1*0602 and DRB1*070101-DQB1*0201 may contribute to the resistance to the development of cervical cancer among Chinese women. The study suggests that specific HLA class II alleles and haplotypes may influence the immune response to specific HPV-encoded epitopes and affect the risk of cervical cancer in a Chinese population from an area with a high incidence of this neoplasia.     

HLA-class II genes in Mexican Amerindian Mayas: relatedness with Guatemalan Mayans and other populations

We analyzed the HLA class II allele frequencies in 50 healthy unrelated Mayan individuals. The relationship with other worldwide populations was studied by using HLA data from 71 different populations. The most frequent alleles were HLA-DRB1*04, HLA-DRB1*01, HLA-DQB1*0302 and HLA-DQB1*0501. When comparisons with other Mexican Amerindian groups were made, some differences were observed. Mayans showed an increased frequency of HLA-DRB1*01 when compared to Nahuas, Mayos, Teenek and Mazatecans (p < 0.05), whereas the HLA-DRB1*04 was increased in Mayans when compared to Nahuas (p < 0.05). The analysis of HLA-DQB1 alleles showed an increased frequency of DQB1*0302 in Mayans when compared to Nahuas and Mazatecans (p < 0.05), whereas the frequency of HLA-DQB1*0301 was decreased in Mayans when compared to Nahuas, Mayos, Teenek and Mazatecans (p < 0.05). Decreased frequency of HLA-DQB1*0501 in Mayans when compared to Nahuas was found. Neighbour Joining dendrogram shows that Mexican Mayans are genetically close to some of the most ancient groups living in Mexico and some South American Amerindians. However, Guatemalan Mayans do not cluster together with Mexican Mayas showing that languages do not correlate with genes, particularly in Amerindians. The data corroborate the restricted polymorphism of HLA-DRB1 and DQB1 alleles and the high frequency of HLA-DRB1*04 and HLA-DQB1*0302 in Mayans from Mexico.     

HPV16 E6 variants and HLA class II polymorphism among Chinese women with cervical cancer

Infection with human papillomavirus type 16 (HPV16) confers a high risk for the development of cervical cancer. Variants of this virus may interact differentially with host genetic factors, possibly affecting the disease pathogenesis. This study was designed to investigate the association between HPV16 E6 variants and human leukocyte antigen (HLA) polymorphism within a Chinese population. Peripheral blood from HPV16 positive Chinese women with cervical carcinoma, who had previously been tested for HPV16 E6 variants, was used for HLA class II typing. It was found that there was a significant positive association between DQB1*060101 allele and HPV16 As variant-positive cervical cancers (OR, 4.47; Pc=0.0018). A negative relationship was found between DRB1*150101-DQB1*0602 haplotype and decreased risk for HPV16 As variant-positive cervical cancers (OR=0.31; P=0.037). Similar tendency was observed for the haplotype DRB1*070101-DQB1*0201 with HPV16 As variant-positive cervical cancers (OR=0.16, P=0.024). Additionally, as for the HPV16 E6 prototype-positive cervical cancers, a significant positive association was found in DQB1*060101 allele (OR=5.95; P=0.002; Pc=0.036), and similar trends were observed for DQB1*030201 (OR=10.87, P<0.0001; Pc=0.0018), and DPB1*1301(OR=7.40, P=0.002; Pc=0.04). It was found that there was no significant association between DRB1-DQB1 haplotype and HPV16 prototype-positive cervical cancers. These data indicate that host genetic factors, such as HLA polymorphism, may determine the potential oncogenicity of the HPV16 E6 variant. The results suggest that a specific match between E6 variant proteins and HLA class II alleles may contribute to HPV16-related cervical carcinogenesis in a certain Chinese population.