血小板特异性基因(HPA-1～17)在广州地区人群中分布的多态性研究

目的:调查在广州地区人群中HPA-1～17基因的多态性及其表达频率。方法:采用序列特异性引物-聚合酶链反应(SSP-PCR)对500名健康的血小板捐献者的HPA基因进行分型。结果:广州地区健康的血小板捐献者中表达出HPA-a基因中的1a～17a基因;各基因独立的分布频率中,HPA-1a(99.8%)、2a(99.85%)、3a(56.3%)、4a(99.9%)、5a(98.8%)、6a(98.6%)、15a(55.1%),HPA-7a～14a、16a、17a均为100%。仅表达HPA-b基因中的1b、2b、3b、4b、5b、6b和15b,分布频率为HPA-1b(0.2%)、2b(0.15%)、3b(43.7%)、4b(0.1%)、5b(1.2%)、6b(1.4%)、15b(44.9%);未表达HPA-7b、8b、9b、10b、11b、12b、13b、14b、16b和17b;说明HPA-1a～17a和HPA-3b、15b在广州地区为高频率基因。在与中国汉族不同地区HPA基因多态性分布的比较分析中发现,广州地区人群中HPA基因频率与北京地区人群的差异较明显;在与部分国家民族人群的比较分析中发现,广州地区人群中HPA基因频率与欧洲、美国、英国和埃及人群有较明显差异,而与日本和泰国人群的差异较小。文中调查和分析了HPA基因组合型及其频率,发现广州地区HPA基因有40种组合型,其中仅有5种基因组合型频率10%(占25%),另外35种基因组合型的频率均9%(占75%)。结论:数据提示广州地区人群中HPA基因遗传距离较接近。HPA基因表达和分布频率在中国汉族人群中存在南北差异。与不同亚洲以外的种族和国家之间亦表现出基因表达和分布的差异。HPA基因多态性研究数据有利于指导地区性血小板供者库库容的设计,配合临床开展选择适合性血小板输注,避免同种免疫造成的血小板输注无效,且对开展HPA相关临床研究具有重要意义。     

海南岛黎族人血小板1～17抗原系统基因多态性研究

目的 调查海南岛黎族人群血小板抗原基因(human platelet alloantigens,HPA)1～17等位基因多态性,分析不同民族的差异,评估其在随机输血中供受者HPA不配合比例,为黎族人群临床血小板输注提供实验依据.方法 采用聚合酶链反应-序列特异性引物方法 对180名黎族人HPA-1～17抗原系统34个等位基因分型.结果 黎族人HPA的等位基因频率分别为:HPA-2a:0.9972,-2b:0.0028,-3a,0.4889,3b:0.5111,5a:0.9667,-5b:0.0333,-6a:0.9972,-6b:0.0028,-15a:0.4250,-15b:0.5750,其余HPA-1、-4、7、-14、-16、-17系统未检出相应HPA-b等位基因.结论 本研究结果 揭示了黎族人HPA-1～17基因型和等位基因频率分布概况,提示黎族人HPA基因频率分布具有黎族人独有的特点.在随机血小板输注中,HPA不配合的机会依次为:HPA-3为37.49%、HPA-15为36.93%、HPA-5为6.23%,只需检测供、受者HPA-3、-5、-15基因相合,就可基本达到血小板匹配性输注.     

海南岛黎族人血小板1～17抗原系统基因多态性研究

目的 调查海南岛黎族人群血小板抗原基因(human platelet alloantigens,HPA)1～17等位基因多态性,分析不同民族的差异,评估其在随机输血中供受者HPA不配合比例,为黎族人群临床血小板输注提供实验依据.方法 采用聚合酶链反应-序列特异性引物方法 对180名黎族人HPA-1～17抗原系统34个等位基因分型.结果 黎族人HPA的等位基因频率分别为:HPA-2a:0.9972,-2b:0.0028,-3a,0.4889,3b:0.5111,5a:0.9667,-5b:0.0333,-6a:0.9972,-6b:0.0028,-15a:0.4250,-15b:0.5750,其余HPA-1、-4、7、-14、-16、-17系统未检出相应HPA-b等位基因.结论 本研究结果 揭示了黎族人HPA-1～17基因型和等位基因频率分布概况,提示黎族人HPA基因频率分布具有黎族人独有的特点.在随机血小板输注中,HPA不配合的机会依次为:HPA-3为37.49%、HPA-15为36.93%、HPA-5为6.23%,只需检测供、受者HPA-3、-5、-15基因相合,就可基本达到血小板匹配性输注.     

海南岛黎族人血小板1～17抗原系统基因多态性研究

目的 调查海南岛黎族人群血小板抗原基因(human platelet alloantigens,HPA)1～17等位基因多态性,分析不同民族的差异,评估其在随机输血中供受者HPA不配合比例,为黎族人群临床血小板输注提供实验依据.方法 采用聚合酶链反应-序列特异性引物方法 对180名黎族人HPA-1～17抗原系统34个等位基因分型.结果 黎族人HPA的等位基因频率分别为:HPA-2a:0.9972,-2b:0.0028,-3a,0.4889,3b:0.5111,5a:0.9667,-5b:0.0333,-6a:0.9972,-6b:0.0028,-15a:0.4250,-15b:0.5750,其余HPA-1、-4、7、-14、-16、-17系统未检出相应HPA-b等位基因.结论 本研究结果 揭示了黎族人HPA-1～17基因型和等位基因频率分布概况,提示黎族人HPA基因频率分布具有黎族人独有的特点.在随机血小板输注中,HPA不配合的机会依次为:HPA-3为37.49%、HPA-15为36.93%、HPA-5为6.23%,只需检测供、受者HPA-3、-5、-15基因相合,就可基本达到血小板匹配性输注.     

广州汉族配偶人类血小板抗原基因分型的调查

目的调查配偶之间人类血小板抗原（HPA）的不配合率并评估其在新生儿同种免疫性血小板减少症（NAIT）中的作用。方法采用SSP法对200对广州汉族配偶进行了HPA-1～-16基因分型。结果配偶双方HPA-1～-6及HPA-15均在同-HPA位点具有不同基因型．HPA-7～-14及HPA-16均为a／a纯合子。得到HPA-1～-16的等位基因频率。HPA．15、HPA-3、HPA-2、HPA-6、HPA-5、HPA-1和HPA一4的不配合率为别为37．42％、37．02％、8．02％、3．84％、2．44％、0．75％和0．24％,其余HPA位点的不配合率为0。结论HPA-5可能是广州汉族人群NAIT最重要的一个HPA系统。HPA-15、HPA-3、HPA-2、HPA-6和HPA-4也分别具有其免疫学意义,这为HPA的抗体检测以及NAIT的诊断治疗提供了实验依据。     

汉族人群血小板同种抗原HPA-3、HPA-9w多态性分布

目的研究我国不同汉族人群血小板同地区种抗原HPA-3、HPA-9w多态性。方法采用聚合酶链反应-序列特异性引物(polymerase chain reaction-sequence specific primers,PCR-SSP)技术对1000名来自不同省份汉族无关献血者进行HPA-3、HPA-9w抗原基因分型。结果在调查的1000名汉族人群中HPA-3a、HPA-3b基因频率分别为0.5935和0.4065,HPA-9全为a/a纯合子。经χ2检测,符合Hardy-Weinberg平衡。不同地区汉族人群之间比较,广东省与陕西、黑龙江、浙江、云南、江苏5省的HPA-3多态性分布差异有统计学意义,其余省份之间多态性分布差异无统计学意义。中国汉族人群与越南人、澳大利亚人HPA-3的多态性分布差异有统计学意义。结论在随机输血中供受者HPA-3抗原不配合比例达0.3661,这为研究同种免疫血小板减少症、开展血小板同型输注提供了理论基础。     

中国山东地区汉族人群血小板特异性抗原-15基因多态性分析

目的:分析山东地区汉族人群血小板特异性抗原(HPA)15基因多态性分布特点。方法:采用PCR-序列特异性引物(PCR-SSP)技术对108例无血缘关系汉族人进行HPA-15基因分型,计算等位基因频率、基因型频率并与其他种族、地区人群相关资料比较。结果:等位基因HPA-15a和HPA-15b分布频率分别为0.5139和0.4861;基因型HPA-15a15b、-15a15a、-15b15b频率依次为0.2407、0.2130、0.5463;HPA-15基因分布与越南、德国、奥地利人近似,而与印地安人差异有显著性(P<0.05)。结论:山东地区汉族人HPA-15基因存在多态性,并具有明显的种族和地域性差异。     

血小板特异性抗体及HLA抗体引起血小板输注无效的研究

目的分析血小板输注无效（PTR）患者血小板同种抗体,并对其HPA及HLA-Ⅰ类抗原进行基因分型,探讨血小板输注无效与血小板同种抗原／HLA—Ⅰ类抗原相关性。方法应用ELISA方法对17例血小板输注无效患者血清中的血小板抗体进行检测;运用PCR—SSP方法,采用HPA分型试剂盒检测血小板同种抗原7个抗原系统HPA-1、2、3、4、5、6、15,以及HLA分型试剂盒对HLA—A／B抗原进行基因分型。结果6名患者单独表达HLA抗体,4名患者表达血小板特异性糖蛋白抗体,3例HLA抗体和血小板特异性糖蛋白抗体共同表达．其中以GPⅡb／Ⅲa为主。对17例患者HPA系统和HLA-Ⅰ类抗原基因分型,发现HPA-3系统中a的基因频率高达0．676,b为0．324;HLA—A＊02、HLA—A＊24、HLA—A＊11和HLA—B＊60、HLA—B＊13、HLA—B＊46多见。结论HLA抗体和血小板特异性糖蛋白抗体表达引起血小板输注无效,了解胛R与HPA／HLA—Ⅰ类抗原的相关性对指导临床血小板配合性输注具有重要意义。     

山西省部分地区汉族人群血小板特异性抗原基因多态性研究

目的研究山西省汉族人群血小板特异性抗原(HPA)基因多态性分布特点,丰富血小板人类遗传学资料,同时为山西地区患者血小板配型提供参考依据。方法本研究使用序列特异性引物-聚合酶链式反应(SSP-PCR)方法,对山西150例汉族成年人进行血小板特异性抗原基因分型检测。结果山西汉族人群血小板特异性抗原HPA 1-17位点中,HPA 1-6,157个位点呈现多态性,基因频率分别是1a 0.997、1b 0.003、2a 0.980、2b 0.020、3a 0.563、3b 0.437、4a0.997、4b 0.003、5a 0.960、5b 0.040、6a 0.970、6b 0.030、15a 0.490、15b 0.510。结论山西省汉族人群血小板特异性抗原有其特有的地域特点,人类血小板特异性抗原基因有明显的地域种族多态性分布规律。     

汉族人血小板GPⅡb HPA-3基因多态性与冠心病的相关性研究

目的： 观察血小板膜糖蛋白（GP）Ⅱb人类血小板抗原-3（HPA-3）基因多态性,在北京河北地区汉族人中各基因型的分布频率,分析该多态性与冠心病易感性的相关性。方法: 本研究采用病例对照设计,筛选符合冠心病、健康人入选标准的212例冠心病患者及106例健康对照人群为研究对象,记录冠脉造影病变支数,采用TaqMan探针技术检测HPA-3基因多态性。结果: 大于45岁的人群中,至少含有1个HPA-3b等位基因者较HPA-3a/3a原生型纯合子,冠心病人(72.4%/27.6%)多于健康人(57.1%/42.9%),不同基因型在冠心病组和健康对照组两组间的分布具有显著差异(P<0.05);冠心病患者不同病变支数基因型构成无显著差异(P＞0.05)。以是否患冠心病为因变量的二分类Binary Logistic回归分析,校正年龄、性别、体重指数对冠心病的影响后,结果显示HPA-3多态位点基因型与冠心病发病密切相关,含有至少1个HPA-3b等位基因者较HPA-3a/HPA-3a纯合型发生冠心病的危险性是2.105倍。结论: GPⅡb的HPA-3多态位点是汉族人冠心病发病的独立危险因素,尤其在年龄＞45岁的人群中表现明显。     

Genetic landscape of human platelet antigen variants in the Indian population analysed from 1029 whole genomes

Genetic variants in human platelet antigens (HPAs) considered allo- or auto antigens are associated with various disorders, including neonatal alloimmune thrombocytopenia, platelet transfusion refractoriness and post-transfusion purpura. Although global differences in genotype frequencies were observed, the distributions of HPA variants in the Indian population are largely unknown. This study aims to explore the landscape of HPA variants in India to provide a basis for risk assessment and management of related complications. Population-specific frequencies of genetic variants associated with the 35 classes of HPAs (HPA-1 to HPA-35) were estimated by systematically analysing genomic variations of 1029 healthy Indian individuals as well as from global population genome datasets. Allele frequencies of the most clinically relevant HPA systems in the Indian population were found as follows, HPA-1a – 0.884, HPA-1b – 0.117, HPA-2a – 0.941, HPA-2b – 0.059, HPA-3a – 0.653, HPA-3b – 0.347, HPA-4a – 0.999, HPA-4b – 0.0010, HPA-5a – 0.923, HPA-5b – 0.077, HPA-6a – 0.998, HPA-6b – 0.002, HPA-15a – 0.582 and HPA-15b – 0.418. This study provides the first comprehensive analysis of HPA allele and genotype frequencies using large scale representative whole genome sequencing data of the Indian population.     

Human platelet antigens: typing by PCR using sequence-specific primers and their distribution in blood donors resident in Wales.

We developed and validated HPA-1 to HPA-6 typing by PCR-SSP using a combination of established, modified and newly designed sequence-specific primers. We confirmed that the PCR primer mixtures functioned under the same PCR conditions as our standard HLA-A, -B, -C, -DR, -DQ PCR-SSP typing system. This allows concurrent testing for both HPA and HLA specificities and is therefore the system of choice for both clinical and large-scale blood donor panel HPA and HLA typing by PCR-SSP. Test validation included typing a population of blood donors living in Wales. These HPA frequencies were consistent with those of other European Caucasoid populations. HPA-4b and -6b were absent and HPA-5b, which shows some frequency variation, had a phenotype frequency of 18.9% (allele frequency 0. 0973), being close to that of the Dutch (19.7%) and Austrian (20.4%) populations and almost twice that found in Finns (10.0%). HPA genotype frequencies showed a good fit to Hardy-Weinberg equilibrium, further supporting the validity of our typing method.     

Human platelet antigens: typing by PCR using sequence-specific primers and their distribution in blood donors resident in Wales

We developed and validated HPA-1 to HPA-6 typing by PCR–SSP using a combination of established, modified and newly designed sequence-specific primers. We confirmed that the PCR primer mixtures functioned under the same PCR conditions as our standard HLA-A, -B, -C, -DR, -DQ PCR–SSP typing system. This allows concurrent testing for both HPA and HLA specificities and is therefore the system of choice for both clinical and large-scale blood donor panel HPA and HLA typing by PCR–SSP. Test validation included typing a population of blood donors living in Wales. These HPA frequencies were consistent with those of other European Caucasoid populations. HPA-4b and -6b were absent and HPA-5b, which shows some frequency variation, had a phenotype frequency of 18.9% (allele frequency 0.0973), being close to that of the Dutch (19.7%) and Austrian (20.4%) populations and almost twice that found in Finns (10.0%). HPA genotype frequencies showed a good fit to Hardy–Weinberg equilibrium, further supporting the validity of our typing method.     

Gene frequencies of human platelet antigens in the Macedonian population

Human platelet antigen (HPA) systems consist of more than 12 bi-allelic antigen polymorphisms. Due to these polymorphisms, platelet-membrane glycoproteins can be recognized as alloantigens or autoantigens and can cause conditions such as fetomaternal alloimmune thrombocytopenia, post-transfusion refractoriness to platelets, and post-transfusion throbocytopenic purpura. The purpose of this study was to investigate the distribution of HPA-1, -2, -3, and -5 in Macedonian population by using the polymerase chain reaction and restriction fragment length polymorphism. The allele frequencies were 0.865 for HPA-1a, 0.135 for HPA-1b, 0.852 for HPA-2a, 0.148 for HPA-2b, 0.578 for HPA-3a, 0.422 for HPA-3b, 0.909 for HPA-5a, and 0.091 for HPA-5b. Results of our study were not significantly different from those reported in the other European studies. Our population displayed the highest frequency for HPA-2b allele (0.148) reported among European population.     

Genotyping for human platelet-specific antigens HPA-1, -2, -3, -4 and -5 in the Slovenian population reveals a slightly increased frequency of HPA-1b and HPA-2b as compared to other European populations

Typing of human platelet alloantigens (HPA) is necessary in various clinical situations. The purpose of this study was to type a random sample of the Slovenian population for HPA alleles, in order to obtain genetic population data. A total of 152 unrelated Slovenian blood donors were genotyped for HPA-1, -2, -3, -4 and -5 alleles using a simple method that enables simultaneous and complete determination of HPA genotypes. Ten different polymerase chain reactions employing sequence-specific priming (PCR-SSP), which worked in identical cycling conditions, were used. The allele frequencies were 0.809 for HPA-1a, 0.191 for HPA-1b, 0.891 for HPA-2a, 0.109 for HPA-2b, 0.591 for HPA-3a, 0.407 for HPA-3b, 0.997 for HPA-4a, 0.00 for HPA-4b, 0.934 for HPA-5a and 0.066 for HPA-5b. When compared to results of studies of various other Caucasian populations, our population displayed a slightly but not significantly higher proportion of the HPA-1b and 2b alleles.     

Genotyping for human platelet-specific antigens HPA-1, -2, -3, -4 and -5 in the Slovenian population reveals a slightly increased frequency of HPA-1b and HPA-2b as compared to other European populations.

Typing of human platelet alloantigens (HPA) is necessary in various clinical situations. The purpose of this study was to type a random sample of the Slovenian population for HPA alleles, in order to obtain genetic population data. A total of 152 unrelated Slovenian blood donors were genotyped for HPA-1, -2, -3, -4 and -5 alleles using a simple method that enables simultaneous and complete determination of HPA genotypes. Ten different polymerase chain reactions employing sequence-specific priming (PCR-SSP), which worked in identical cycling conditions, were used. The allele frequencies were 0.809 for HPA-1a, 0.191 for HPA-1b, 0.891 for HPA-2a, 0.109 for HPA-2b, 0.591 for HPA-3a, 0.407 for HPA-3b, 0.997 for HPA-4a, 0.00 for HPA-4b, 0.934 for HPA-5a and 0.066 for HPA-5b. When compared to results of studies of various other Caucasian populations, our population displayed a slightly but not significantly higher proportion of the HPA-1b and 2b alleles.     

Human platelet alloantigens (HPAs): PCR-SSP genotyping of a UK population for 15 HPA alleles.

Alloimmunization to human platelet alloantigens (HPAs) is responsible for neonatal alloimmune thrombocytopenia (NAIT), post-transfusional purpura (PTP) and platelet transfusion refractoriness. HPAs may also have a role as histocompatibility antigens in transplantation as well as associations with cardiac disease. We have developed a polymerase chain reaction-sequence-specific primer (PCR-SSP) assay capable of detecting 15 HPA allelic variants. As part of the validation of the assay, 134 UK renal donors were genotyped to determine HPA allele frequencies in the UK population. The HPA allele frequencies obtained are consistent with those of the other European studies: GP1A*1 (HPA-5a) and GP1A*2 (HPA-5b), 0.914 and 0.086, respectively; GP1BA*1 (HPA-2a) and GP1BA*2 (HPA-2b), 0.925 and 0.075; GP2B*1 (HPA-3a) and GP2B*2 (HPA-3b), 0.627 and 0.373; GP3A*1 (HPA-1a) and GP3A*2 (HPA-1b), 0.840 and 0.161. The rare alleles GP2B*3 (HPA-9bw) and GP3A*3 to *8 (HPA-4b, -6b, -7bw, -8bw, -10bw and -11bw, respectively) were all absent. This comprehensive HPA genotyping assay allows rapid, accurate and reproducible results at low cost.     

HPA polymorphism in sub-Saharan African populations: Beninese, Cameroonians, Congolese, and Pygmies

The frequency of human platelet antigen-1 (HPA-1) to HPA-11w (excluding HPA-8w) and HPA-15 systems was studied in four sub-Saharan populations: Beninese, Congolese (Democratic Republic of Congo Kinshasa), Cameroonians, and Aka pygmies (Central African Republic). No report of HPA prevalence has previously been published concerning these populations which are characterized by the highest HPA-2b gene frequencies of any reported to date (Aka 0.393, Benin 0.292, Cameroon 0.237, and Congo 0.224) and at lesser degree HPA-5b (Aka 0.405, Congo 0.268, Cameroon 0.254, and Benin 0.182). This study is of great importance (i) particularly in the context of the diversity caused by the population migrations, we may observe today in our hospitals (ii) to confirm that the Pygmy population with distinctive frequencies (absence of the HPA-1b, HPA-2b, and HPA-5b highest frequencies) is an isolated population.     

Human platelet alloantigen systems in three Chinese ethnic populations

Knowledge of the prevalence of human platelet antigens (HPA) in different populations is important for effective diagnosis and management of immune-mediated platelet disorders. The purpose of this study was to determine HPA gene frequencies in the majority Han ethnic population of China and in ethnic She and Tajik minority populations. Using PCR sequence specific primers, HPA- 1, -2, -3, -4, -5, and -6, we determined genotypes for ethnic Han, She, and Tajik blood donors. HPA gene frequencies for Chinese Han were found to be similar to those of She, reflecting the historic affinities of these two populations. HPA gene frequencies for Tajik were closer to those for Caucasians than to Chinese Han, She, or other Asian populations, reflecting their disparate origin and historic geographic isolation. HPA gene frequencies in these Chinese populations reflect their historic origins. Knowledge of these findings may be used to better understand and treat immune-mediated platelet disorders in these populations.