兰州地区汉族人群HLA-A、B和DRB1等位基因多态性分析

目的分析兰州地区汉族人群HLA-A、B和DRB1位点等位基因多态性特点。方法采用序列特异性引物聚合酶链反应技术对兰州地区200名健康无血缘关系的汉族个体HLA-A、B和DRB1基因座进行分型，并与西北、北方和南方汉族、西北回族、维吾尔族和藏族人群进行比较。结果兰州汉族人群中HLA-A基因座共检出14个等位基因，以A＊02，A＊11，A＊24，A＊33，A＊30，A＊01和A＊31基因最常见；HLA—B基因座共检出32个等位基因，以B＊40，B＊15，B＊46，B＊13，B＊51，B＊60，B＊58和B＊44基因最为常见；HLA-DRB1基因座共检出13个等位基因，最多见的基因依次为DRB1＊09．DRB＊15，DRB1＊12，DRB1＊04，DRB1＊11，DRB1＊07，DRB1＊08和DRB1＊14，接近北方汉族而与南方汉族有差异，与西北回族无明显差异，但与西北维吾尔族和藏族差异有统计学意义。结论兰州地区汉族人群HLA-A、B和DRB1位点等位基因多态性与南、北汉族人群存在不同程度的差异，与西北维吾尔族和藏族差异显著。     

HLA-B新的等位基因B*5136的确认和分析

目的研究HLA-B新的等位基因B＊5136的分子机理。方法先证者为浙江省脐带血造血干细胞捐献者。盐析法抽提样本DNA，常规PCR反应扩增先证者HLA-B基因第2～4外显子的编码序列，PCR产物经TOPO试剂盒克隆转染到质粒载体中，分离其两个等位基因，对所得的克隆用第2、3、4外显子引物进行双向测序分析。结果先证者HLA-B基因经TOPO克隆后得到两个等位基因，一个为HLA-B＊4601，另一个经BLAST HLA验证为新的等位基因，其序列已递交GenBank（AY601729，AY610730，AY601731）。新的等位基因与最接近的B＊5108等位基因比较，在第3外显子上有4个核苷酸的差异：第527位T→A，导致第177位氨基酸Val→Glu；第583位C→T，导致第195位氨基酸His→Tyr；在第559位C→A和第560位T→C，导致第187位氨基酸Leu→Thr。结论该脐血捐献者的HLA-B为新的等位基因，被世界卫生组织HLA命名委员会正式命名为HLA→B＊5136。     

Analysis of the HLA-A,-B allele polymorphism in 5844 umbilical cord blood samples taken from Han population of Shandong province

To investigate the HLA-A, -B allele polymorphism in Han population of Shandong province and to explore the possibility to find out the HLA-A, -B-matched cord blood donors for stem cell transplantation to be used in other area in China, 5844 umbilical cord blood samples were taken from Han population donors of Shandong province, and assayed with PCR-sequence-oligonucleotide (PCR-SSO) assay. In Shandong Han donors, 20 alleles at HLA-A locus and 46 alleles at HLA-B locus could be detected as revealed in the present study. Among the 20 alleles at HLA-A locus, the most prevalent five alleles included A * 02(0.3041), A * 11(0.1443), A * 24(0.1434), A * 30(0.0975) and A * 33(0.0859), while, the alleles with lower gene frequencies included A * 34(0.0006), A * 25 (0.0005), A*66(0.0005), A* 74(0.0004) and A* (0.0001). Of the 46 HLA-B alleles detected, the most prevalent five alleles were B * 13(0.1348), B * 51(0.0713), B * 62(0.0712), B * 61 (0.0676) and B * 60(0.0642); while alleles with lower gene frequencies included B * 77(0.0001), B * 76(0.0002), B * 47(0.0003), B * 42(0.0003) and B * 72(0.0004). In comparison with those of the other Han population in China, the HLA-A, -B gene frequencies in the umbilical cord blood of Shandong province possess unique distribution features among the investigated populations from various regions of the same race origin, and the differences in various regions of the same race were less than those among the different race. It is evident that the HLA-A,-B alleles of the umbilical cord blood taken in Shangdong province show high degree of polymorphism, and it might be part of those of Northern Han population in China. So, it is reasonable for patients of Northern Chinese to receive HLA class I -match transplant of cord blood stem cells for tissue and organ transplantation from Shangdong umbilical cord blood bank.     

Parkin基因启动子区-258T/G多态性与广西地区散发性帕金森病的相关性分析

Objective To investigate the association between the-258T/G polymorphism.in the pro-moter of parkin gene and the risk for sporadic parkinson's disease (SPD) in Guangxi Province, and in relationto the age of onset, of PD patients. Methods PCR-RFLP and sequence analysis were used to determine thegenotype of-258T/G polymorphism between all patients and healthy controls. Results The G allele was morecommon in patients than controls (55.20%:43.33% ,x2=6.898, P<0.05, OR=1.61, 95% CI: 1.13 ～2.30). The frequency of GG genotype was higher in patients than in controls (28.00 %: 18.33%, x2=7.159, P<0.05, OR=2.75, 95% CI : 1.31 ～ 5.77). The frequency of TG + GG genotype was higher in pa-tients than in controls (82.40%:68.33%, x2=6.551, P<0.05, OR=2.17.95%CI: 1.20 ～3.93). Afterbeing stratified by onset age, the frequencies of the G allele and GG genotype were significantly higher in pa-tients with onset age over 50 years than those in controls respectively. On the other hand, the frequency was notsignificantly different between the younger onset PD patients and the controls. Conclusion The parkin promot-er-258T/G polymorphism might be a risk factor for PD in Guangxi Province, and the G allele was increasedwith increasing age.     

汉族HLA-A等位基因与银屑病患者相关性研究

目的 探讨HLA-A等位基因与汉族人银屑病遗传易感性。方法 利用聚合酶链反应-序列特异性引物（PCR-SSP）法，对200例银屑病患者和204例健康人的HLA-A等位基因进行检测。结果 HLA-A*2601-05等位基因与汉族人银屑病呈正相关性（20.25%vs12.25%,RR=1.65,X^2=11.76,P=0.0006,Pc=0.0066),HLA-A*0201-17等位基因与汉族人银屑病呈负相关（4.25%vs9.80%,RR=0.43,X^2=10.26,P=0.0013,Pc=0.0143),HLA-A*2601-05等位基因仅与有家族史银屑病呈正相关（RR=2.04,X^2=12.49,P=0.0004,Pc=0.0044),HLA-A*2601-05等位基因与I型银屑病呈正相关（RR=1.68,X^2=11.67,P=0.0006,Pc=0.0066)。结论 HLA-A*2601-05可能是银屑病的易感基因或与易感基因相连锁。HLA-A*2601-05仅为有家族史银屑病和I型银屑病的危险基因。     

湖南汉族人群HLA-DP、-DQ位点等位基因多态性与鼻咽癌的相关性

目的 探讨湖南汉族人群HLA—DP、HLA—DQ位点等位基因多态性与鼻咽癌遗传易感性之间的关系。方法 应用聚合酶链反应—特异性寡核苷酸探针基因分型技术对87例湖南汉族鼻咽癌患者与91名健康对照作HLA—DPAl、—DPBl、—DQAl及—DQBl的基因分型，采用x^2检验比较两组各位点等位基因频率，单倍型频率分布的差异。结果 发现鼻咽癌组DPAl*0201、DPBl*1901、DQAl*0201较对照组明显降低，DPBl*0402、DQAl*0101较对照组明显升高；单倍型DPAl*0201—DPBl*1401及DQAl*0201—DQBl*0201较对照明显降低；但P值经Bonferroni校正后，差异均无显著性(Pc＞0．05)。结论 湖南汉族人群HLA—DP和—DQ位点与鼻咽癌无明显相关，与以往用受累同胞对方法在鼻咽癌家系中未能证实鼻咽癌易感基因与HLA—DP和—DQ位点连锁的结果一致。     

HLA-DRB1*0301等位基因与Graves病的关系

目的 探讨HLA-DRB1*0301等位基因在粤西湛江沿海地区Graves病(GD)发病中的作用.方法 选取65例初诊GD病人和正常对照50例并采用多聚酶链反应-序列特异性引物(PCR-SSP)技术检测HLA-DRB1*0301等位基因的表达频率.结果 初诊GD病人HLA-DRBl*0301等位基因的表达频率显著高于正常对照组(P＜0.005).结论 HLA-DRB1*0301等位基因可能是粤西湛江地区GD的易感基因.     

湖南汉族人群MICA基因多态性分析

为了解湖南地区汉族人群MICA基因第2、3和4外显子多态性分布特点,采用PCR-SSP方法对162名无亲缘关系湖南汉族人群MICA等位基因进行分析。结果显示:在湖南汉族人群中共检测出12个等位基因和28种基因型,各等位基因分布频率有差异,其中以MICA*00801基因频率最高(37.9%),其次为MICA*00201/020(20.1%)和MICA*010(17.3%),频率最低的是MICA*019和MICA*031。将MICA基因在湖南汉族人群中的分布与该基因在其他人群中的分布进行比较,显示MICA基因的分布在不同人群之间存在差异,可作为中国人群的遗传标志。     

Associations of IFN-γ rs2430561 T/A,IL28B rs12979860 C/T and ERα rs2077647 T/C polymorphisms with outcomes of hepatitis B virus infection：a meta-analysis

Several studies investigated associations of IFN-γ rs2430561 T/A,IL28 B rs12979860 C/T and ERα rs2077647 T/C gene polymorphisms with outcomes of hepatitis B virus（HBV） infection,but the results were controversial.Therefore,we performed a meta-analysis of all published observational studies to address this inconsistency.Literature was searched in online database and a systematic review was conducted based on the search results.A total of 24 studies were included and dichotomous data were presented as odds ratio（OR） with a 95%confidence interval（CI）.The rs2430561 T allele was associated with reduced persistent HBV infection risk（T vs.A：OR,0.690;95%CI,[0.490,0.971]）,while the rs2077647 T allele significantly increased the risk of persistent HBV infection（T vs.C：OR.1.678;95%CI,[1.212,2.3231）.Rs 2077647 CC might play a role in protecting individuals against HBV persistence（TT vs.CC：OR,4.109;95%CI,[2.609,6.473]）.Furthermore,carriers of the rs2430561 TT genotype were more likely to clear HBV spontaneously compared with those of the AA genotype（TT vs.AA：OR,0.555;95%CI,[0.359,0.856]）.For rs12979860 C/T polymorphism,no significant correlation with HBV infection outcomes was found.In subgroup analyses,the results were similar to those of overall analysis.However,for rs2077647 TT vs.TC＋CC,significantly increased risks were observed in the Asian and hospital-based population,but not in the overall analysis.IFN-γrs2430561 T/A and ERα rs2077647 T/C genetic polymorphisms were associated with outcomes of HBV infection,but no association was found between IL28 B rs12979860 C/T and HBV infection.     

五例样本HLA-C基因测序分型中等位基因丢失及其原因分析

目的 探讨HLA-C基因测序分型时等位基因漏检和丢失的原因,以提高HLA测序分型的成功率和准确性.方法 620份随机选择的深圳健康捐血者血样,采用AlleleSEQR HLA-C plus测序分型试剂盒进行检测,对无完全匹配、分型结果"异常"的标本,采用分子克隆和测序方法进行全长单倍体序列分析;对未检出新的碱基点突变的样本,进一步采用自行设计的PCR引物和AlleleSEQR试剂盒中的测序引物进行再测序,分析测序分型结果"异常"的原因.结果 620份经AlleleSEQR HLA-C测序分型的样本中,发现5例样本无完全匹配的基因型,与之最接近的多种等位基因型均存在单个碱基的不匹配;并且在第4外显子出现碱基杂合,但第2和第3外显子区域内无杂合碱基.经分子克隆和单倍体测序,以及采用自行设计的PCR引物和AlleleSEQR试剂盒中的测序引物再测序,证实了5例标本均存在Cw * 0706等位基因漏检和丢失现象,未发现新的碱基点突变.结论 HLA-C基因测序分型时,因PCR引物与模板DNA不匹配会导致等位基因的漏检和丢失.根据中国人群HLA-C分子全长序列特点,开发适合于中国人群的测序分型试剂十分必要.