Article

Letter to the Editor

Ann Lab Med 2020; 40(6): 493-499

Published online November 1, 2020 https://doi.org/10.3343/alm.2020.40.6.493

Copyright © Korean Society for Laboratory Medicine.

Human Platelet Antigen Datasets for Malays, Chinese, and Indians in Peninsular Malaysia

Che Ghazali Norul Hajar, M.DSc.1 , Zulkifli Zefarina, M.D., M.Path.2 , Nor Suhaila Md. Riffin, M.D., M.Path.3 , Tuan Hulwani Tuan Mohammad, M.D., M.Path.4 , Mohd Nazri Hassan, M.D., M.Path.2 , Ameer Mohamed Dafalla, Ph.D.5 , Gehad ElGhazali, M.D., M.Path.6 , Geoffrey Keith Chambers, Ph.D.7 , and Hisham Atan Edinur, Ph.D.1

1School of Health Sciences, Universiti Sains Malaysia, Health Campus, Kubang Kerian, Kelantan, Malaysia; 2Hospital Universiti Sains Malaysia, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia; 3Hospital Sultan Haji Ahmad Shah, Temerloh, Pahang, Malaysia; 4Hospital Seberang Jaya, Perai, Pulau Pinang, Malaysia; 5HLA Laboratory, National Cancer Institute, University of Gezira, Wad Medani, Sudan; 6Department of Immunology, Pathology and Laboratory Medicine Services, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates; 7School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand

Correspondence to: Hisham Atan Edinur, Ph.D.
School of Health Sciences Health Campus, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia
Tel: +60 9-7677641, Fax: +60 9-7677515, E-mail: edinur@usm.my

Received: January 31, 2020; Revised: March 7, 2020; Accepted: May 21, 2020

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Dear Editor,

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.

We are grateful to the volunteers and patients who contributed to this study. We specifically thank all the nurses and doctors who helped collect the blood samples.

HPA allele frequency distribution in the present and previous studies

Population(N)1a1b2a2b3a3b4a4b5a5b6a6b15a15b
Malays (present study)970.9850.0150.9690.0310.5100.4901.0000.0000.9900.0100.9900.0100.4790.521
Chinese (present study)771.0000.0000.9800.0200.5910.4101.0000.0000.9870.0130.9940.0060.5260.474
Indians (present study)470.9790.0210.9690.0310.5210.4791.0000.0000.9590.0410.9900.0100.3750.625
Banjar [3]301.0000.0000.9500.0500.6160.3840.9500.0500.9500.0500.9800.0200.4800.520
Bugis [3]371.0000.0001.0000.0000.5540.4461.0000.0000.9500.0500.9100.0900.6200.380
Champa [3]510.9800.0200.9700.0300.6770.3231.0000.0000.9900.0100.9800.0900.4800.520
Jawa [3]391.0000.0001.0000.0000.6280.3721.0000.0000.9600.0401.0000.0000.4500.550
Kelantan [3]351.0000.0000.9400.0600.5710.4291.0000.0001.0000.0000.9900.0100.4900.510
Orang Kanaq [4]111.0000.0001.0000.0000.8180.1821.0000.0001.0000.0001.0000.0000.9090.091
Batek [4]271.0000.0001.0000.0000.5000.5001.0000.0000.8520.1481.0000.0000.0001.000
Lanoh [4]251.0000.0001.0000.0000.6400.3601.0000.0001.0000.0001.0000.0000.2600.740
Kensiu [4]360.9580.0421.0000.0000.8750.1251.0000.0000.8470.1531.0000.0000.3610.639
Che Wong [4]261.0000.0001.0000.0000.4230.5771.0000.0000.7880.2121.0000.0000.5000.500
Semai [4]400.9880.0121.0000.0000.6710.3291.0000.0000.8900.1101.0000.0000.5240.476
Malays [6]2000.9750.0250.9630.0370.5030.4970.9950.0050.9500.0500.9930.0070.5150.485
Chinese [6]2001.0000.0000.9670.0330.5730.4270.9980.0020.9830.0170.9830.0170.4980.502
Indians [6]2000.8850.1150.9600.0400.6200.3800.9950.0050.9400.0600.9950.0050.4080.592

Homogeneity between pairs of population groups in Peninsular Malaysia

HPA-1

MalaysChineseIndiansBanjar [3]Bugis [3]Champa [3]Jawa [3]Kelantan [3]O. K. [4]Batek [4]Lanoh [4]Kensiu [4]C. W. [4]Semai [4]Malays [6]Chinese [6]Indians [6]
Malays*0.257NANA0.558NA0.5570.568NANANA0.340NANANANA<0.000
Chinese0.088*0.145NANA0.158NANANANANA0.032NA0.344NANA<0.000
Indians1.0000.294*0.5200.501NA0.4990.507NA0.5340.5440.6500.538NANANA0.004
Banjar [3]0.4410.0630.669*NA0.530NANANANANA0.241NANANANA0.003
Bugis [3]0.1841.0000.2540.085*0.508NANANANANA0.114NANANANA<0.000
Champa [3]0.2091.0000.3490.1931.000*0.5040.516NA0.539NA0.6450.545NANANA0.003
Jawa [3]0.1831.0000.2490.076NA1.000*NANANANA0.108NANANANA0.001
Kelantan [3]0.4530.0340.4501.0000.0520.1600.046*NANANA0.239NANANANA<0.000
O. K. [4]1.0001.0001.0000.551NA1.000NA0.557*NANANANANANANA0.162
Batek [4]0.3401.0000.5460.239NA1.000NA0.127NA*NA0.252NANANANA0.004
Lanoh [4]0.3431.0000.5450.241NA1.000NA0.135NANA*0.263NANANANA0.008
Kensiu [4]0.1901.0000.2550.088NA1.000NA0.052NANANA*NANANANA0.159
C.W [4]0.3381.0000.2550.242NA1.000NA0.131NANANANA*NANANA0.005
Semai [4]0.1781.0000.2490.076NA1.000NA0.043NANANANANA*NANA0.004
Malays [6]0.8120.0351.0000.713NA0.079NA0.4980.6230.2230.3860.1390.2300.086*NA<0.000
Chinese [6]0.8570.2000.7820.4920.3430.2720.3520.3600.7050.4390.6600.6620.3500.5430.857*<0.000
Indians [6]1.0000.1061.0000.5420.2690.1960.2800.4260.6410.4590.4380.2710.4590.2771.0000.836*
HPA-2

HPA-3

MalaysChineseIndiansBanjar [3]Bugis [3]Champa [3]Jawa [3]Kelantan [3]O. K. [4]Batek [4]Lanoh [4]Kensiu [4]C. W. [4]Semai [4]Malays [6]Chinese [6]Indians [6]
Malays*0.1320.2510.186<0.0010.0020.1160.6000.0160.8710.038<0.0010.4190.0160.7110.1900.018
ChineseNA*0.5220.960<0.0010.2630.8990.8910.1920.1930.467<0.0010.0480.3760.1360.8720.784
IndiansNANA*0.5840.0190.1300.4020.5260.0600.2360.381<0.0010.1390.3760.4340.3880.297
Banjar [3]0.0130.0190.075*0.0140.6381.0000.8040.3320.2060.7220.0030.0630.6750.2390.7610.297
Bugis [3]NANANA0.085*0.0250.0060.0010.016<0.0010.160<0.001<0.0010.002<0.001<0.0010.955
Champa [3]NANANA0.047NA*0.6020.1860.5720.0140.9000.0120.0030.5900.0010.0600.009
Jawa [3]NANANA0.077NANA*0.7000.3460.150.6610.0020.0380.7430.1050.6580.099
Kelantan [3]NANANA0.095NANANA*0.1050.6050.337<0.0010.1720.3480.5540.9690.964
O. K. [4]NANANA0.551NANANANA*0.0250.3730.4670.0030.6720.0080.1010.694
Batek [4]NANANA0.238NANANANANA*0.050<0.0010.6670.0480.6300.2800.216
Lanoh [4]NANANA0.240NANANANANANA*0.0090.0150.4480.0560.2570.279
Kensiu [4]NANANA0.089NANANANANANANA*<0.0010.020<0.001<0.001<0.001
C.W [4]NANANA0.242NANANANANANANANA*0.0060.3410.0690.009
Semai [4]NANANA0.073NANANANANANANANANA*0.0080.1840.523
Malays [6]NANANA0.002NANANANANANANANANANA*0.1270.009
Chinese [6]NANANANANANANANANANANANANANA0.368*0.396
Indians [6]NANANANANANANANANANANANANANA0.368*
HPA-4

HPA-5

MalaysChineseIndiansBanjar [3]Bugis [3]Champa [3]Jawa [3]Kelantan [3]O. K. [4]Batek [4]Lanoh [4]Kensiu [4]C. W. [4]Semai [4]Malays [6]Chinese [6]Indians [6]
Malays*1.0000.0931.0000.0491.0000.1421.0001.000<0.001<0.0011.000<0.0011.0000.7230.7230.008
Chinese1.000*0.2001.0000.0881.0000.3331.0001.000<0.001<0.0011.000<0.0010.5461.0001.0000.038
Indians1.0001.000*0.1540.7230.1931.0000.1341.0000.0230.0100.2920.0030.1250.2330.2290.834
Banjar [3]0.5560.4841.000*0.1221.0000.254NANA0.001<0.001NA<0.001NA0.5960.5980.203
Bugis [3]0.0010.0010.0180.068*0.1580.7090.1160.5590.0990.0450.1400.0120.0490.0710.0711.000
Champa [3]1.0001.0001.0001.0000.009*0.3181.0001.000<0.001<0.0011.000<0.0011.0001.0001.0000.098
Jawa [3]0.1430.1090.3210.6280.1900.312*0.2411.0000.0420.0180.2710.0040.1150.2140.2120.813
Kelantan [3]1.0001.0001.0000.4590.0111.0000.240*NA<0.001<0.001NA<0.001NA0.5970.5950.093
O. K. [4]1.0001.0001.0001.0000.1771.0001.000NA*0.074NA0.0460.018NA1.0001.0000.635
Batek [4]1.0001.0001.0001.0000.0161.0000.267NANA*0.0041.0000.568<0.001<0.001<0.0000.028
Lanoh [4]1.0001.0001.0001.0000.0361.0000.275NANANA*0.001<0.001NA1.0001.0000.242
Kensiu [4]1.0001.0001.0000.4550.0101.0000.241NANANANA*0.589<0.001<0.001<0.0000.013
C.W [4]1.0001.0001.0001.0000.0351.0000.265NANANANANA*<0.001<0.001<0.0000.002
Semai [4]1.0001.0001.0000.4280.0041.0000.113NANANANANANA*0.6040.6010.295
Malays [6]0.7220.4481.0001.0000.0021.0000.211NANANANANANANA*1.0000.003
Chinese [6]0.7240.4501.0001.0000.0021.0000.210NANANANANANANA1.000*0.003
Indians [6]0.6021.0000.4740.344<0.0010.4920.032NANANANANANANA0.1690.175*
HPA-6

HPA-15

MalaysChineseIndiansBanjar [3]Bugis [3]Champa [3]Jawa [3]Kelantan [3]O. K. [4]Batek [4]Lanoh [4]Kensiu [4]C. W. [4]Semai [4]Malays [6]Chinese [6]Indians [6]
Malays*0.5030.2170.0870.0490.4070.7320.007<0.001<0.0010.0190.1440.0130.2550.6870.9040.176
Chinese**0.0330.0220.0650.1270.5210.001<0.001<0.0010.0020.0470.0700.0910.7230.6380.012
Indians***0.1200.0070.3080.3750.029<0.001<0.0010.4430.6060.0030.1470.0410.0700.866
Banjar [3]****0.3000.6260.0460.8620.013<0.0010.0800.020<0.0010.7940.0500.0490.109
Bugis [3]*****0.2600.0310.1160.080<0.0010.0020.003<0.0010.4750.0770.0450.004
Champa [3]******0.2470.2270.002<0.0010.0630.082<0.0010.8620.2400.2570.340
Jawa [3]*******0.006<0.001<0.0010.0570.5410.0890.1100.4480.6030.309
Kelantan [3]********0.013<0.0010.0310.003<0.0010.4280.0020.6030.011
O. K. [4]*********<0.001<0.001<0.001<0.001<0.0010.001<0.001<0.001
Batek [4]**********<0.001<0.001<0.001<0.001<0.001<0.001<0.001
Lanoh [4]***********0.352<0.0010.0330.0020.0030.183
Kensiu [4]************0.0260.0300.0370.0660.323
C.W [4]*************<0.0010.0100.0090.001
Semai [4]**************0.1880.1720.136
Malays [6]***************0.8750.006
Chinese [6]****************0.014
Indians [6]*****************

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