Human platelet antigens (HPAs) are genetically inherited polymorphic glycoproteins expressed on the platelet membrane [1]. HPAs are transfusion and gestation compatibility determinants, and HPA alloantibodies have been reported in post-transfusion purpura, platelet transfusion refractoriness, and neonatal alloimmune thrombocytopenia (NAIT) cases [2].

Previously, we reported HPA allele frequency data for Malay subethnic groups [3] and Orang Asli [4] in Peninsular Malaysia. These earlier studies have provided a valuable preliminary source of genetic information for health assessments and population genetics. However, a complete picture of the genetic structure in Peninsular Malaysia should also include data from Malays (i.e., Deutero-Malays), Chinese, and Indians, as they represent >75% of the total population [5]. There are some HPA data for Malays, Chinese, and Indians reported by Tan, et al. [6]; the present HPA data can be compared with those data.

We typed HPA-1 to −6 and HPA-15 loci in blood samples obtained with informed consent from a total of 222 individuals registered as voluntary, non-remunerated blood donors at the Hospital Universiti Sains Malaysia (Kelantan), Hospital Seberang Jaya (Pulau Pinang), and Temerloh Hospital (Pahang) in Malaysia. The individuals were un-admixed with no history of intermarriage with other ethnic groups for three generations. The ethnicity classes of these samples were assigned as Malay (N=97), Chinese (N=77), and Indian (N=48) based on individual pedigree information. Our proposed study was reviewed and approved by the Human Ethical Committee, Universiti Sains Malaysia, Malaysia, and the Medical Research and Ethics Committee, Ministry of Health, Malaysia. The HPA typing and data analysis were performed as previously described by Wan Syafawati, et al. [3] and Syafawati et al. [4]. Briefly, isolated genomic DNA was amplified using polymerase chain reaction and sequence-specific primers (PCR-SSP) for HPA-1 to −6 and −15. Amplified products were then separated using agarose gel electrophoresis (2% agarose gels stained with ethidium bromide) and visualised using a UV photometer (Quantum ST4-1000/20M, VilberLourmat, Deutschland GmbH, Eberhardzell, Germany). The separated band patterns (amplified allele-specific HPA products and human growth hormone) were then compared with a 100 base pair DNA size standard (Bioline, London, UK). HPA allele frequencies were determined by dividing the allele count numbers by the total numbers of chromosomes (2n) tested. Genetic differentiations between pairs of HPA population datasets were evaluated using Arlequin version 3.0 software [7] and were considered statistically significant at P<0.05.

The present and previously reported HPA datasets of various population groups in Peninsular Malaysia are shown in Table 1 [3, 4, 6]. These HPA datasets reveal that Malays and Chinese differ significantly (P<0.05) from Indians (Table 2). However, no significant differences were observed between the HPA datasets of Malays and Chinese. Importantly, Malays, Chinese, and Indians are the modern-day descendants of ancestrally unrelated ethnic groups in Peninsular Malaysia; the inability of the HPA datasets to differentiate between Malays and Chinese needs to be resolved using more informative genetic markers, including genome-wide single nucleotide polymorphisms and whole genome sequencing data [8]. In addition, some of the ancestral relationships might also be obscured by demographic processes such as natural selection and founder effects. Of these forces, natural selection is expected to have a greater effect on genes that are important in the medical field such as HPA, compared with other regions in the human genome [1]. For example, some differences observed between ancestrally related Proto-Malays (Orang Kanaq), Malay subethnic groups, and Malays could possibly be attributed to gene flow via admixture and historical events at the population level (as mentioned earlier), rather than different origins (Table 2) [8].

In our view, HPA datasets for various population groups in Peninsular Malaysia (Tables 1 and 2) also have significant value for health and have been identified as genetic risk factors for many diseases [9]. The risk of HPA alloimmunization in Peninsular Malaysia might be expected to be most frequently associated with alloantibodies against HPA-3 and HPA-15 products, as these are the most polymorphic loci observed within and between population groups in Peninsular Malaysia (Tables 1 and 2). Our hypothesis regarding HPA alloimmunization risk is supported by the presence of HPA-1a, -3a, -5a, and -15b alloantibodies in most of the NAIT cases and multi-transfused thrombocytopenia patients in Malaysia [10]. Therefore, implementation of HPA typing could reduce the incidence of HPA alloimmunization cases in Malaysia.

In conclusion, to the best of our knowledge, our study is the first complete representative collection of HPA datasets for all population groups in Peninsular Malaysia. These datasets can be used for developing better healthcare services and as a reference standard for identifying genetic risk factors for many diseases associated with HPAs.