According to many reports, the sole allele found in HPA4, 6, and 9 is usually a, thus leading to the aa genotype in all participants in this study. analysis shows that the HPA2 and HPA5 have the greatest differences in genotype distribution between the Iranians and other nations, although similar to other populations, the sole allele found in HPA4, 6, and 9 is usually a. Fidarestat (SNK-860) Despite other HPAs, the most frequent allele in HPA15 is usually b, which is also abundant in HPA3. Hierarchical clustering indicates the highest degree of global similarity in HPA genotype frequency among Iranian, Argentinian, Brazilian, and German Turkish populations. Our findings can be applied to decrease the risk of alloimmunizations and platelet disorders, especially in neonates. strong class=”kwd-title” Subject terms: Classification and taxonomy, Structural variation, Coagulation system, Immunogenetics, Genetics research Introduction Platelets are tiny, essential blood components that were previously considered only in homeostasis by adherence to damaged vessels, thus creating clots with fibrin to prevent bleeding. Nowadays, they have Fidarestat (SNK-860) been assigned a much greater diversity of roles beyond clotting, such as in inflammation, innate and adaptive immunity1,2, proving these small objects to be critical in a wide range of diseases1. Most platelet functions are performed by binding to other cells through membranous glycoproteins (GPs). On these GPs, there are polymorphic amino acid sequences called human platelet antigens (HPAs), which are considered alloantigens due to their polymorphism3. So far, 41 types of HPA have been serologically identified, the naming of which is usually in the order of recognized identification4. Twelve antigens, including HPA-1a/1b, -2a/2b, -3a/3b, -4a/4b, -5a/b, and -15a/b are biallelic and located on GPIIIa, GPIba, GPIIb, GPIIIa, GPIa and CD109, respectively5. HPAs are inherited in a codominant autosomal way, and the most frequent allele is called a6,7. Their polymorphism is mainly because of the alteration of an Fidarestat (SNK-860) amino acid within their structure, following a single nucleotide polymorphism (SNP). One amino acid alteration can cause a change in the tertiary structure of the antigen, leading to new epitope creation capable of inducing the alloantibodies production3. Incompatibility in platelet antigens between mother and fetus during pregnancy or donor and recipient in case of blood transfusion can induce alloantibodies which may destroy platelets, thus creating thrombocytopenia and various hemorrhagic disorders, including fetal and neonatal alloimmune thrombocytopenia (FNAIT), post-transfusion purpura Fidarestat (SNK-860) (PTP) and multi-transfusion platelet refractoriness (MPR)5,8,9. Thrombocytopenia is usually a common, fatal complication in hematological diseases, which proves the importance of HPAs in clinical researches more than before. The most immunogenic HPAs are HPA1a and HPA5b, which are responsible for inducing more than 90% of antiplatelet alloantibodies10. The frequency of HPAs varies among populations, and thorough knowledge of HPA frequencies among different populations can play an important role in reducing antigen differences between donor and recipient, hence diminishing the risk of alloimmunization. In fact, determining HPA allele and genotype frequency among populations can provide a significant basis in reducing the problems associated with the HPA-mediated alloreactions in suspected or highly alloimmunized individuals. This study represents the first report of HPA1-6, HPA9, and HPA15 allele and genotype frequency Rabbit Polyclonal to ACTN1 within the Iranian population, with a comparison of such frequencies to those reported in former studies. Results Intra-population study The allele and genotype frequencies of HPA1-6, 9, and 15 in 300 healthy Iranian subjects are illustrated in Table?1. The distribution of the genotypes for all those HPA genes does not show any significant deviation from the Hardy-Weinberg equilibrium (HWE), except for HPA5, which is different from HWE (p-value=0.011, X2?=?6.33). In contrast to other HPAs, the most frequent allele seen in HPA15 is usually b (54%), with the highest ratio of ab and bb genotype frequencies (49.3 and 29.4%, respectively). HPA3 has also a high proportion of allele b (41.3%), with a high frequency of ab and bb genotypes (43.3 and 19.7%, respectively). The greatest amount of a allele can be observed in HPA4, 6, and 9, which comprises all alleles, without any b allele. Accordingly, all the genotypes in HPA4, 6, and 9 are aa, and no ab or bb genotypes is usually detected. The only HPA having the allele b, but no homozygous bb genotype, is usually HPA1, in which all the allele b is in the heterozygous form. Table 1 Allele and genotype distribution of HPA1-6, 9 and 15 in the Iranian population. thead th rowspan=”1″ colspan=”1″ HPA /th th Fidarestat (SNK-860) rowspan=”1″ colspan=”1″ Alleles/genotypes /th th rowspan=”1″ colspan=”1″ Healthy Control N (%) /th th rowspan=”1″ colspan=”1″ Pa /th /thead HPA1a541.