小儿急性淋巴细胞白血病HLA-A,B等位基因多态性研究

 目的 研究北方汉族人群儿童急性淋巴细胞性白血病（ALL）患者与HLA-A,B等位基因多态性的遗传关联。方法 采用聚合酶链反应-序列特异性寡核苷酸探针（PCR-SSO）方法,对197例北方汉族儿童ALL患者和5 841例健康脐带血样本HLA-A,B等位基因多态性进行研究。结果 在HLA-A,B等位基因中,儿童ALL患者的A11,A24,B40,B15,B56,B67,B27等基因的基因频率都显著高于正常人群,而HLA-B48基因的基因频率显著下降（P＜0.05）。结论 HLA-A11,A24,B15,B58,B67,B27等基因对儿童ALL患者有遗传易感作用,尤其是B40与ALL具有强相关性;而HLA-B48基因对儿童ALL患者有遗传拮抗作用。     

人类白细胞抗原Ⅰ、Ⅱ类等位基因及单倍体多态性与中国南方汉族白血病的相关性

目的探讨人类白细胞抗原(HLA)Ⅰ类(A、B、C)、Ⅱ类(DRB1、DQB1、DPB1)等位基因和单倍体多态性与中国南方汉族急性淋巴细胞白血病(ALL)、急性髓系白血病(AML)以及慢性粒细胞白血病(CML)的相关性。方法收集深圳市血液中心845例中国南方汉族白血病患者(323例ALL、350例AML及172例CML)和745名中国南方汉族健康献血者的外周血样本。应用聚合酶链反应反向序列特异性寡核苷酸探针杂交(PCR-rSSO)及测序分型(PCR-SBT)方法对HLA-A、-B、-C、-DRB1、-DQB1和-DPB1进行基因分型,鉴定HLA等位基因前4位数。采用Arlequin 3.5软件分析HLA单倍体;从HLA低分辨水平(等位基因前2位数)及高分辨水平(等位基因前4位数)分别统计分析HLA等位基因和单倍体多态性与3种白血病的相关性。结果经Bonferroni校正,ALL组A*02(36.22%比28.26%,χ²=13.41,PC<0.01)及其单倍体A*02-B*46-C*01(15.35%比10.23%,χ²=10.90,PC=0.02)、DRB1*12(15.79%比11.10%,χ²=9.02,PC=0.03)、A*02:03(9.75%比5.32%,χ²=14.25,PC=0.002)及其单倍体A*02:03-B*38:02-C*07:02(3.80%比1.51%,χ²=10.41,PC=0.02)的频率均高于对照组,是ALL易感因素;AML组A*11-B*15-C*08-DRB1*15-DQB1*06-DPB1*02的频率高于对照组(1.34%比0.07%,χ²=12.54,PC=0.003),是AML易感单倍体;CML组A*02(36.63%比28.26%,χ²=9.33,PC=0.02)及其单倍体A*02-B*15-C*04(2.17%比0.29%,χ²=11.74,PC=0.02)、DRB1*03:01-DQB1*02:01-DPB1*02:01(1.86%比0.14%,χ²=13.10,PC=0.01)的频率均高于对照组,是CML易感因素;CML组DRB1*13的频率低于对照组(1.45%比5.25%,χ²=9.29,PC=0.03),是CML拮抗基因。结论在HLA低分辨及高分辨水平发现了白血病易感或拮抗HLA等位基因和单倍体,可为探究中国南方汉族白血病发病机制并制订有效治疗策略提供参考。     

B7-H4基因多态性与黑龙江省乳腺癌易感性的研究

 目的　探讨B7-H4基因 rs10754339、rs10801935和rs3738414等SNP位点多态性与黑龙江省妇女乳腺癌发病风险的相关性。方法　利用聚合酶链反应限制性片段长度多态性（PCR-RFLP）技术,对287例黑龙江省汉族女性乳腺癌患者和305名健康对照者进行B7-H4基因位点多态性检测,并确定常见单体型（频率≥1 %）,分析患者与健康对照差异,进而确定该基因与黑龙江省汉族妇女乳腺癌的相关性。结果　B7-H4基因3'-UTR区rs10754339位点的G等位基因、AA、AG基因型发生频率在乳腺癌组和健康对照组间差异有统计学意义（P＝0.030,OR 1.359,95 % CI 1.030～1.794;P＝0.018,OR 0.671,95 % CI 0.482～0.935;P＝0.029,OR 1.455,95 % CI 1.038～2.038）。5'-UTR区rs3738414位点的A等位基因、GG基因型和AG基因型发生频率在乳腺癌患者和健康对照组之间差异有统计学意义（P＝0.0008,OR 0.604,95 % CI 0.455～0.803;P＝0.001,OR 1.804,95 % CI 1.289～2.253;P＝0.005,OR 0.612,95 % CI 0.435～0.862）。AAA单体型和GAG单体型发生频率在乳腺癌患者和健康对照组之间差异有统计学意义（P＝0.0015,OR 0.614,95 % CI 0.456～0.828;P＝0.0003,OR 1.954,95 % CI 1.363～2.803）。结论　B7-H4基因多态性与黑龙江省汉族妇女乳腺癌发病存在一定相关性。     

SBT、SSOP法分析湖北土家族妇女HLA-A2超型各等位基因及与宫颈癌的关联

目的通过检测湖北土家族人群HLA-A2超型(包含A*0201、A*0202、A*0203、A*0204、A*0205、A*0206、A*0207、A*6802、A*6901)各等位基因,分析与宫颈癌关联的等位基因及其结构与功能特点.方法提取湖北土家族正常人群236名育龄妇女及59例原发性宫颈癌患者外周血DNA,采用SBT(sequence based typing)、SSOP(Sequence Specific Oligonucleotide Probes)HLA基因分型技术,对HLA-A2超型各等位基因型进行分型,比较宫颈癌病例组和正常对照组中HLA-A2超型中相应等位基因型构成比的差异,并分析相关等位基因的结构特点.结果有7种HLA-A2超型等位基因HLA-A*0201(17.3%)HLA-A*0202(9.5%)HLA A*0203(1.4%)HLA-A*0204(3.8%)HLA-A*0205(3.1%)HLA-A*0206(10.8%)HLA-A*0207/0215N(9.8%),其中HLA-A*0202和HLA A*0206在正常对照组和宫颈癌病人组的构成比有显著性差异(p＜0.05),HLA-A*0202(OR=0.24,95%CI=0.05～0.48)和HLA A*0206(OR=0.2,95%CI=0.67～1.07)对于宫颈癌发生的易感性有保护作用.结论湖北土家族人群HLA-A*0201所占比例最高达17.3%,HLA-A*0202和HLA-A*0206对于宫颈癌发生的易感性有保护作用.     

亚甲基四氢叶酸还原酶基因单核苷酸多态性与儿童急性淋巴细胞白血病的相关性

 【摘要】　目的　探讨亚甲基四氢叶酸还原酶基因（MTHFR）单核甘酸多态性与儿童急性淋巴细胞白血病（ALL）发病风险的关系。方法　分别收集45例ALL患儿（ALL组）及45名健康儿童（对照组）外周血各2 ml,提取基因组DNA,应用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）法,检测MTHFR C677T和A1298C基因型,比较不同基因型对儿童ALL发病风险的影响。采用Logistic回归模型计算比值比（OR）和95 %可信区间（95 % CI）。结果　对照组MTHFR 677CC、CT和TT基因型基因分布频率分别为31.1 %（14／45）、51.1 %（23／45）和17.7 %（8／45）,ALL组3种基因型分布频率分别为51.1 %（23／45）、40.0 %（18／45）和8.9 %（4／45）,两者比较差异有统计学意义（χ2＝7.48,P＝0.04）;MTHFR 677 T等位基因在ALL组中的检出率为48.8 %（22／45）,在对照组中的检出率为69.9 %（31／45）;T等位基因携带者发生ALL的风险是CC基因型的0.4倍（95 % CI 0.21～0.83）。对照组MTHFR 1298AA、AC和CC基因型基因分布频率分别为57.8 %、40.0 %和2.2 %,ALL组中3种基因型分布频率分别为18.8 %、44.4 %和6.8 %,两者比较差异无统计学意义（χ2＝11.23,P＝0.23）;MTHFR 1298 C等位基因ALL组中的检出率为42.2 %（19／45）,对照组中的检出率为51.1 %（23／45）;C等位基因的存在并不会提高儿童ALL发生的风险（OR＝1.3,95 % CI 0.21～0.83）。结论　MTHFR 677 T等位基因的存在会显著降低儿童发生ALL的风险,而MTHFR 1298各基因型与儿童ALL的发生均无明显相关性。     

PTEN、MLL基因在T淋巴母细胞淋巴瘤／白血病的表达及其意义

 目的　分析肿瘤抑制基因PTEN、混合系白血病（MLL）基因等在T淋巴母细胞淋巴瘤／白血病（T-LBL／ALL）的表达及意义。方法　选用76例T-LBL／ALL患者淋巴结存档蜡块,应用免疫组织化学EnVision法进行PTEN标记,用20例反应性增生淋巴结标本作正常对照。并用荧光原位杂交（FISH）技术检测MLL基因所在11q23染色体的断裂和扩增情况。结果　76例T-LBL／ALL中,PTEN的表达率为64.47 %（49／76）,低于淋巴结反应性增生的100 %（20／20）（χ2＝19.220,P＜0.05）。PTEN表达与临床分期、Ki-67、乳酸脱氢酶（LDH）呈负相关（P＜0.05）。76例T-LBL／ALL中,MLL基因发生11q23染色体断裂13例（17.11 %）,扩增18例（23.68 %）。MLL基因断裂组总体生存率（25.0 %）低于非断裂组（43.6 %）（χ2＝11.357,P＜0.05）。MLL基因扩增组总体生存率（17.1 %）低于非扩增组（42.7 %）（χ2＝4.533,P＜0.05）。结论　抑癌基因PTEN表达降低在T-LBL／ALL的发生发展中可能具有重要作用。MLL基因发生染色体11q23断裂和扩增有助于对T-LBL／ALL预后的判断,发生MLL基因断裂或扩增的T-LBL／ALL预后较差,提示MLL基因断裂或扩增可能为T-LBL／ALL的一种分子亚型。     

乙酰肝素酶Arg307Lys多态性与成年人急性白血病发病风险的关系

 目的　探讨乙酰肝素酶（HPSE）Arg307Lys 多态性与成年人急性白血病发病风险的关系。方法　按照1∶1配对病例对照研究方法,选择中国北方地区100例急性髓系白血病（AML）和25例急性淋巴细胞白血病（ALL）患者为病例组,100名中国北方地区健康人为对照组,采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法检测观察对象外周血HPSE Arg307Lys基因多态性。结果　成年ALL病例组和对照组Lys／Lys、Arg／Lys、Arg／Arg基因型分布频率分别为80 %、16 %、4 %和75 %、23 %、2 %,两组比较差异无统计学意义（χ2＝0.07,P＝0.79;χ2＝0.08,P＝0.78）。AML病例组Lys／Lys、Arg／Lys、Arg／Arg基因型频率分别为85 %、14 %、1 %,与对照组比较差异无统计学意义（χ2＝3.03,P＝0.08;χ2＝3.15,P＝0.08）。携带HPSE Arg307Lys突变基因（AA／AA+AG）的个体不增加AML及ALL的发病风险（AML：χ2＝3.13,P＝0.07,OR＝1.89,95 %CI 0.93～3.83;ALL：χ2＝0.27,P＝0.60,OR＝1.33,95 %CI 0.45～3.90）。结论　HPSE Arg307Lys与中国北方地区急性白血病的发生可能无关。     

急性淋巴细胞白血病患者 ASB2和 Jak3基因mRNA 表达的研究

目的：研究急性淋巴细胞白血病（ALL）患者骨髓中锚蛋白重复序列和抑制细胞因子信号盒蛋白2（ASB2）和 Janus 激酶3（Jak3）mRNA 的表达及其两者的相关性。方法收集初诊的48例 ALL患者（37例 B 细胞 ALL,11例 T 细胞 ALL）和34例非白血病患者（对照组）骨髓,采用实时荧光定量 PCR检测骨髓中 ASB2和 Jak3 mRNA 表达情况。结果B 细胞 ALL 和 T 细胞 ALL 患者骨髓中 ASB2 mRNA表达量相对于对照组分别升高了32．7倍和68．5倍,差异均有统计学意义（t ＝20．1,P ＜0．01;t ＝23．1, P ＜0．01）,Jak3 mRNA 表达量较对照组分别升高了2336．3和7131．5倍（t ＝70．2,P ＜0．01;t ＝90．4, P ＜0．01）。ASB2和 Jak3 mRNA 表达量具有相关性（r ＝0．523,P ＜0．001）。结论ASB2和 Jak3在 ALL患者骨髓中异常表达,且具有正相关性,两者可能共同参与白血病细胞的恶性增殖和异常分化。     

维吾尔族霍奇金淋巴瘤与HLA-DRB1、DPA1基因多态性的相关性研究

目的：探索人类白细胞抗原（HLA）DRB1和DPA1低分辨等位基因型与维吾尔族霍奇金淋巴瘤（HL）易感性的关系。方法：采用病例-对照研究（1∶2）和DNA直接测序分型（SBT）法,对40例维吾尔族HL患者和80名健康体检者进行HLA-DRB1及DPA1基因分型,分析其与HL发病的相关性。结果：对于HLA-DRB1和DPA1基因,病例组分别检出12和3个低分辨等位基因,对照组中分别检出13和4个低分辨等位基因;HLA-DRB1、DPA1基因座位上等位基因频率分布均满足Hardy-Weninberg遗传平衡检验（P > 0.05）。维吾尔族HL中HLA-DRB1*15、DPA1*03、DPA1*02-DRB1*13基因表达均高于维吾尔族健康对照组（P均<0.05）;而HLA-DRB1*07基因频率低于维吾尔族健康对照组（P < 0.05）。结论：HLA-DRB1、DPA1基因多态性可能与维吾尔族HL的发病存在关联,在揭示HL的发病机制方面有研究价值。     

急性白血病患者WT1基因表达水平及其临床意义

目的：探讨WT1基因与急性髓系白血病（AML）、急性淋巴细胞白血病（ALL）患者预后的关系及其用于微小残留病（MRD）监测的可能性。方法收集58例初发AML、32例初发ALL、40例AML-完全缓解（CR）、28例ALL-CR患者及31例同期三系增生活跃患者（对照组）骨髓单个核细胞,利用荧光定量聚合酶链反应（PCR）方法检测WT1基因的表达,建立WT1基因在各组间的表达阈值,以WT1拷贝数／ABL拷贝数×100%表示WT1基因的相对表达量。结果初发AML患者与对照组间WT1基因中位相对表达量差异有统计学意义[20.880%（3.550%～48.500%）比0.026%（0～0.240%）,Z＝-7.74,P＜0.0001]。AML-CR患者[0.102%（0～5.380%）]与初发AML患者间WT1基因中位相对表达量差异有统计学意义（Z＝-8.34,P＜0.0001）。此外,WT1基因表达高于阈值（20.880%）的AML患者第1个疗程CR率为60.7%（17／28）,而表达低的患者为76.7%（23／30）。AML患者复发时WT1表达升高。与对照组相比,初发ALL患者WT1基因中位相对表达量[0.350%（0.021%～10.780%）]升高（Z＝-2.58,P＜0.05）,但与ALL-CR患者[0.038%（0～2.800%）]相比,WT1基因中位相对表达量差异无统计学意义（P＝0.065）。结论 WT1基因在AML中的表达相对较高,其可能成为AML患者预后评估及MRD监测的有效指标,但并不适用于ALL患者。     

Susceptible and Protective Associations of HLA Alleles and Haplotypes with Cervical Cancer in South India

Background: Human leukocyte antigen (HLA) genes have been implicated in cervical cancer in several populations. Objectives: To study the predispositions of HLA alleles/haplotypes with cervical cancer. Materials and Methods: Clinically diagnosed and PAP smear confirmed cervical cancer patients (n 48) and age matched controls (n 47) were genotyped for HLA-A,-B,-DRB1* and DQB1* alleles by PCR-SSP methods. Results: The frequencies of alleles DRB1*04 (OR=2.57), DRB1*15 (OR=2.04), DQB1*0301 (OR=4.91), DQB1*0601 (OR=2.21), B*15 (OR=13.03) and B*07 (OR=6.23) were higher in cervical cancer patients than in the controls. The frequencies of alleles DRB1*10 (OR=0.22) and B*35 (OR=0.19) were decreased. Strong disease associations were observed for haplotypes DRB1*15-DQB1*0601 (OR=6.56; < 3.5.10-4), DRB1*14-DQB1*0501 (OR=6.51; <0.039) and A*11-B*07 (OR=3.95; <0.005). The reduced frequencies of haplotypes DRB1*10-DQB1*0501 (OR=0.45), A*03-B*35 (OR=0.25) and A*11-B*35 (OR= 0.06) among patients suggested a protective association. HLA-C* typing of 8 patients who possessed a unique three locus haplotype 'A*11-B*07-DRB1*04' (8/48; 16.66%; OR=6.51; <0.039) revealed the presence of a four locus haplotype 'A*11-B*07-C*01-DRB1*04' in patients (4/8; 50%). Amino acid variation analysis of susceptible allele DQB1*0601 suggested 'tyrosine' at positions 9 and 37 and tyrosine-non-tyrosine genotype combination increased the risk of cervical cancer. Conclusions: Strong susceptible associations were documented for HLA alleles B*15, B*07, DRB1*04, DRB1*15, DQB1*0301, DQB1*0601 and haplotypes DRB1*15-DQB1*0601 and DRB1*14-DQB1*0501. Further, protective associations were evidenced for alleles B*35 and DRB1*10 and haplotypes A*11-B*35 and DRB1*10-DQB1*0501 with cervical cancer in South India.     

Meningioma: is there an association with human leukocyte antigens?

The expression of human leukocyte antigen (HLA) alleles plays an important role in the development and recurrence of benign and malignant diseases. Association of single HLA alleles or haplotypes with neoplastic processes has been investigated previously, and correlation between HLA and solid tumors, such as head and neck cancers or uterine cervical squamous epithelial lesions, were reported. However, there is no published data on the influence of the HLA system on the development of symptomatic cerebral meningioma, a mostly benign intracranial tumor of mesenchymal origin in adults. The present investigation is comparing the frequency of single HLA alleles and haplotypes in 81 adult Caucasian patients with symptomatic central nervous system meningiomas to that of 157 area- and race-matched healthy controls. Both standard serological and molecular genetic (PCR) techniques were used for HLA typing. Our results suggest an association between single HLA alleles and occurrence of clinically symptomatic meningioma. Patients with HLA-A*02 had a 2.5-fold increased risk of meningioma (P = 0.02), and those with HLA-DQB1*05 had a 1.8-fold increased risk of meningioma (P = 0.05). Conversely, HLA-A*01, -B*08, and -DRB1*03 were associated with a 0.4-, 0.5-, and 0.5-fold, respectively, decreased risk of meningioma (P = 0.008, P = 0.05, and P = 0.04). Moreover, the occurrence rate of combinations and estimated haplotypes containing these HLA alleles was strikingly different in meningioma patients compared with controls: significantly increased for the haplotypes HLA-A*02:DRB1*04 (P = 0.02, relative risk = 2.5) and HLA-A*02:DRB1*04:DQB1*0302,DQB1*05 (P = 0.03, RR = 7.5), and significantly decreased for the haplotype HLA-A*01:B*08:DRB1*03 (P = 0.01, relative risk = 0.2). In conclusion, these data suggest that some single HLA alleles and haplotypes may protect from or predispose to developing symptomatic central nervous system meningioma during adult life. These associations may be indicative of the involvement of the immune system in the host antitumor surveillance, recognition, and destruction of de novo arising human tumor cells.     

Association of HLA class I and II alleles and extended haplotypes with nasopharyngeal carcinoma in Taiwan

BACKGROUND: Nasopharyngeal carcinoma (NPC), which occurs at a disproportionately high rate among Chinese individuals, is associated with Epstein-Barr virus (EBV). Human leukocyte antigen (HLA) polymorphisms appear to play a role in NPC, because they are essential in the immune response to viruses. We used high-resolution HLA genotyping in a case-control study in Taiwan to systematically evaluate the association between various HLA alleles and NPC. METHODS: We matched 366 NPC case patients to 318 control subjects by age, sex, and geographic residence. Participants were interviewed and provided blood samples for genotyping. High-resolution (polymerase chain reaction-based) genotyping of HLA class I (A and B) and II (DRB1, DQA1, DQB1, and DPB1) genes was performed in two phases. In phase I, 210 case patients and 183 control subjects were completely genotyped. In phase II, alleles associated with NPC in the phase I analysis were evaluated in another 156 case patients and 135 control subjects. Extended haplotypes were inferred. RESULTS: We found a consistent association between HLA-A*0207 (common among Chinese but not among Caucasians) and NPC (odds ratio [OR] = 2.3, 95% confidence interval [CI] = 1.5 to 3.5) but not between HLA-A*0201 (most common HLA-A2 allele in Caucasians) and NPC (OR = 0.79, 95% CI = 0.55 to 1.2). Individuals with HLA-B*4601, which is in linkage disequilibrium with HLA-A*0207, had an increased risk for NPC (OR = 1.8, 95% CI = 1.2 to 2.5) as did individuals with HLA-A*0207 and HLA-B*4601 (OR = 2.8, 95% CI = 1.7 to 4.4). Individuals homozygous for HLA-A*1101 had decreased risks for NPC (OR = 0.24, 95% CI = 0.13 to 0.46). The extended haplotype HLA-A*3303-B*5801/2-DRB1*0301-DQB1*0201/2-DPB1*0401, specific to this ethnic group, was associated with a statistically significantly increased risk for NPC (OR = 2.6, 95% CI = 1.1 to 6.4). CONCLUSIONS: The restriction of the association of HLA-A2 with NPC to HLA-A*0207 probably explains previously observed associations of HLA-A2 with NPC among Chinese but not Caucasians. The extended haplotypes associated with NPC might, in part, explain the higher rates of NPC in this ethnic group.     

HLA-A,HLA-B,HLA-DRB1 Polymorphisms and Risk of Cervical Squamous Epithelial Cell Carcinoma: A Population Study in China

Cervical cancer is the second most common cancer in women. HLA class I and II alleles polymorphismshave been shown to be associated with cervical cancer risk, but results have varied among different populations.In this study, the HLA-A, -B, and –DRB1 alleles among 100 southern Chinese women with cervical squamouscell carcinoma (SCC) were compared to 254 controls. Our results showed that B*51:01:02 allele frequencywas significantly higher in patients with SCC than in healthy controls (P = 3.17x 10-5, Pc = 0.005, OR = 26.7).Statistical analysis also revealed a significantly decreased frequency of B*51:01:01 (P = 7.01x 10-4, Pc = 0.03, OR= 0.12) in patients with SCC when compared with healthy controls. These results indicate that HLA-B*51:01:02may confer susceptibility to SCC and HLA-B*51:01:01 may contribute to resistance to the development of SCCin Chinese women. None of the HLA-A-B or HLA-A-B-DRB1 haplotypes were significantly different in casesand controls after multiple testing corrections, indicating the individual allele associations to be independent ofthe identified haplotypes. These results support the hypothesis that some HLA-B alleles could be involved withsusceptibility for developing SCC.     

Selected class I and class II HLA alleles and haplotypes and risk of high-grade cervical intraepithelial neoplasia

Human leukocyte antigens (HLAs) present foreign antigens to the immune system and may be important determinants of cervical neoplasia. Previously published associations between HLA and cervical neoplasia exhibit considerable variation in findings. The biomarkers of cervical cancer risk (BCCR) case-control study addressed the role of specific HLA alleles as cofactors in the development of high-grade cervical intraepithelial neoplasia (HG-CIN) based on the most consistent evidence from published literature. Cases (N = 381) were women with histologically-confirmed HG-CIN attending colposcopy clinics and controls (N = 884) were women from outpatient clinics with normal cytological screening smears. Subjects were mainly of French-Canadian descent. Cervical specimens were tested for human papillomavirus (HPV) DNA and HLA genotypes by PGMY L1 consensus primer PCR and a PCR sequence-specific primer method, respectively. Unlike other studies, the DQB1*03 and DRB1*13 allele groups were not associated with risk of HG-CIN. The B7-DRB1*1501-DQB1*0602 haplotype was associated with a 41% overall reduction in HG-CIN risk (odds ratio [OR] = 0.59; 95% confidence interval [CI]: 0.36-0.96), and an 83% reduction in risk of HG-CIN among HPV 16 or HPV 18-positive subjects (OR = 0.17; 95%CI: 0.05-0.54). Paradoxically, however, the same haplotype was associated with HPV 16/18 infection risk among controls (OR = 8.44, 95%CI: 1.12-63.73). In conclusion, the B7-DRB1*1501-DQB1*0602 haplotype was protective against HG-CIN, especially in individuals infected with oncogenic HPV, but the mechanism of the association seems to involve multiple steps in the natural history of HPV and CIN.     

Positive and negative associations of human leukocyte antigen variants with the onset and prognosis of adult glioblastoma multiforme.

Associations of genetic factors with malignant gliomas have been modest. We examined the relationships of human leukocyte antigen (HLA) and related polymorphisms to glioblastoma multiforme in adult Caucasians (non-Hispanic Whites) from the San Francisco Bay area. For 155 glioblastoma multiforme patients and 157 control subjects closely matched by ethnicity, age, and gender, PCR-based techniques resolved alleles at HLA-A, -B, -C, and -DRB1 loci along with short tandem repeat polymorphisms of MICA exon 5 and TNFb. By multivariable logistic regression, B*13 and the B*07-Cw*07 haplotype were positively associated with glioblastoma multiforme (P=0.01 and <0.001, respectively), whereas Cw*01 was the only variant showing a negative association (P=0.05). Among glioblastoma multiforme patients, progression to death after diagnosis was slower in those with A*32 (relative hazard, 0.45; P<0.01) and faster in those with B*55 (relative hazard, 2.27; P<0.01). Thus, both the occurrence and the prognosis of glioblastoma multiforme could be associated with specific but different HLA genotypes. B*07 and the B*07-Cw*07 haplotype are much more common in Caucasians than other ethnic groups in the U.S., which may partially explain the higher incidence of glioblastoma multiforme in Caucasians.     

Human Leukocyte Antigen (HLA)-DRB1*14 Is Associated with a High Incidence of Acute Lymphocytic Leukemia

Background: Genetic background and environmental factors play an interactive role in the development of acute lymphocytic leukemia (ALL), and the human leukocyte antigen (HLA) system was noted as an important genetic factor in ALL. Material and Methods: Due to the high diversity of HLA alleles, our present study assessed the possibility of an association of HLA molecules in ALL patients living in Jiangsu Province, Eastern China. HLAA, -B, and -DRB1 allele distributions in 156 ALL patients (aged 3-54 years) were analyzed and compared with unrelated healthy hematopoietic stem cell donors from the same ethnic and geographic background. Results: No significance was found at HLA-A, -B loci between the ALL group and the control group. However, a significant difference was discovered at HLA-DRB1*14 (8.65% in the ALL group versus 4.8% in the control group, pC < 0.05), with an odds ratio of 1.87 (95% confidence interval 1.26- 2.80). Conclusion: HLA-DRB1*14 may be associated with susceptibility to ALL acquisition among the Jiangsu Han population.     

Human leukocyte antigens in Indian patients with chronic myeloid leukemia

In chronic myeloid leukemia (CML), experimental studies using synthetic peptides identical to the bcr-abl fusion region have revealed the capability of specific peptides to bind to human leukocyte antigen (HLA) class I molecules (HLA-A2, A3, A11, B8) and class II molecules (HLA-DR1, DR2, DR3, DR4 and DR11). Individuals expressing HLA-A3, B8 or DR4 have a diminished risk for the development of CML in Caucasian populations. A statistically significant increase in the frequency of Cw3 and Cw4 antigens in Caucasians and European CML patients has been reported. However, HLA associations in CML have not been reported in India. In lieu of the allelic diversity of HLA in the Indian population, the present study assessed the possibility of an association of HLA molecules in Indian patients with CML. HLA A, B, C and DRB1 antigen associations in 180 clinically diagnosed Indian CML patients (aged 17 - 54 years) were analysed and compared with age-matched (n = 100) healthy individuals from the same ethnic background. In the HLA class I antigen distribution, a significant decrease was observed in HLA-A11 (25.6% versus 39%; P = 0.027, odds ratio (OR) = 0.54, 95% confidence interval (CI) = 0.31 - 0.94) and HLA-Cw6 (7.8% versus 20%; P = 0.005, OR = 0.34, 95% CI = 0.15 - 0.74). Among the DRB1 alleles, HLA-DRB1*13 (7.8% versus 17%; P = 0.031, OR = 0.41, 95% CI = 0.18 - 0.93) was decreased in CML patients. However, the differences for HLA-A11 (P(c) = 0.351) and DRB1*13 (P(c) = 0.403) did not remain significant after the application of a correction factor for the P-value. These results suggest that the development of CML is apparently associated with HLA phenotypes specific to each population and indicate that expression of HLA-Cw6 may result in a protective effect on CML acquisition in the Indian population.