Study On Genetic Polymorphism Of The Human Platelet Alloantigens And Its Applications

Human platelet alloantigens(HPA)are specific antigens carried by platelet glycoproteins.Currently,22 kinds of platelet alloantigens have been officially named by the Platelet Nomenclature Committee(PNC),including 6 known systems:HPA-1～5,15.These 22 antigens were distributed in the platelet glycoproteins:GPⅡb,GPⅢa,GPⅠb,GPⅠaCD109.In the view of immunology,HPA can induce alloantibodies bringing about alloimmune response,leading to alloimmune thrombocytopenia.In clinic,HPA is responsible for post-transfusion thrombocytopenic purpura(PTP),platelet transfusion refractoriness(PTR),neonatal immune thrombocytopenic purpura(NAITP),and graft versus host disease.Therefore,accurate detection and identification of HPA is of great significance for blood transfusion practice and clinical medicine.On the other hand,from the perspective of human genetics,the platelet-specific antigen belongs to codominant genetic system with double isoloci,and its gene shows single nucleotide polymorphism(SNP).There exists racial difference in the distribution of HPA polymorphism.Genetic polymorphism analysis of multiple HPA systems can accurately estimate genetic distance between different populations,and analyze human migration process.In order to reduce platelet transfusion alloimmunite reaction,with the support of research project "transfusion safety" from the shanghai health bureau and the grant from the shanghai natural science foundation,our group carried on a project of"study on human platelet alloantigens genotyping and platelet transfusion safety".Through a large investigation in HPA gene frequencies in China Hans,and study HPA which close related to platelet transfusion,then establish a useful HPA-typed plateletpheresis donor registry,we clinically developed the platelet-matched transfusion,which has been proved as a good treatment by now.As a part of above research project,this study is described as follow,1.We investigated allele frequency distribution of HPA-3 and HPA9w antigen in the Chinese Han population from 7 provinces,and compared their genetic polymorphism differences in people from different areas.Investigation of the distributions of HPA-3 and HPA-9w in 1000 Chinese donors was carried out by using a polymerase chain reaction with sequence specific primers(PCR-SSP)method.All participants in this study were informed,and the consent was obtained.Gene frequencies of 1000 Chinese Hans for HPA-3a and HPA-3b were 0.5935 and 0.4065 respectively,and all of HPA-9 were a / a homozygous.P values are greater than 0.05 by Hardy-weinberg test,which confirmed that the results coincided with the Hardy Weinberg equilibrium law,and the data of this investigation were reliable.Compared polymorphism distribution among different Han population,there was significant difference between Guangdong province and other 5 provinces:Shanxi,Heilongjiang, Zhejiang,Yunnan and Jiangsu(P＜0.05),but no difference was found between the remaining provinces(P＞0.05).In comparison to other ethnic groups,no significant differences were observed in the distributions of HPA-3 except the Tunisian Vietnamese and Australian.The chances of incompatibility in random platelet transfusion were 0.3661 for donor and recipient HPA-3 antigens,which provided a theoretical basis for further study on alloimmune thrombocytopenia and HPA-matched transfusion in clinic.2.Utilizing investigation findings of HPA genetic polymorphism in Chinese Han population provided by our research group,we analyzed and compared distributional difference of polymorphism of HPA-1～3,5 and 15 in different populations with the help of reference data,meanwhile estimated the genetic distance among Chinese and foreign people and mapped the phylogenetic tree using DISPAN software.This study demonstrated on one aspect that "Out-of-Africa Theory",confirmed the oriental migration route is from Southeast Asia(India)to Eastern Asia(China),and inferred occidental migration route is from southem Europe(Croatia,Spain)to northern part (Denmark,Ireland).