Literature DB >> 26131415

Allele and Haplotype Frequencies of Human Leukocyte Antigen-A, -B, -C, -DRB1, and -DQB1 From Sequence-Based DNA Typing Data in Koreans.

Ji Won In1, Eun Youn Roh1, Sohee Oh2, Sue Shin1, Kyoung Un Park1, Eun Young Song3.   

Abstract

BACKGROUND: Data on allele frequencies (AFs) and haplotype frequencies (HFs) of HLA-C and -DQB1 are limited in Koreans. We investigated AFs and HFs of HLA-A, -B, -C, -DRB1, and -DQB1 in Koreans by high-resolution sequence-based typing (SBT).
METHODS: Hematopoietic stem cells were obtained from 613 healthy, unrelated donors to analyze HLA-A, -B, -C, -DRB1, and -DQB1 genotypes by using AlleleSEQR HLA-A, -B, -C, -DRB1, and -DQB1 SBT kits (Abbott Molecular, USA), respectively. Alleles belonging to HLA-C*07:01/07:06 group were further discriminated by using PCR-sequence specific primer analysis. AFs and HFs were calculated by direct counting and maximum likelihood method, respectively.
RESULTS: In all, 24 HLA-A, 46 HLA-B, 24 HLA-C, 29 HLA-DRB1, and 15 HLA-DQB1 alleles were identified. AFs and HFs of HLA-A, -B, and -DRB1 were similar to those reported previously. For the HLA-C locus, C*01:02 was the most common allele, followed by C*03:03, C*03:04, C*14:02, C*03:02, and C*07:02 (AF ≥7%). AFs of C*07:01 and C*07:06 were 0.16% and 3.18%, respectively. For the HLA-DQB1 locus, DQB1*03:01 was the most common allele, followed by DQB1*03:03, *03:02, *06:01, *05:01, *04:01, and *06:02 (AF ≥7%). AFs of DQB1*02:01 and DQB1*02:02 were 2.12% and 6.69%, respectively. HFs of A*33:03-C*07:06 and C*07:06-B*44:03 were 3.09% and 3.10%, respectively, while those of DRB1*07:01-DQB1*02:02 and DRB1*03:01-DQB1*02:01 were 6.61% and 2.04%, respectively.
CONCLUSIONS: This study reported AFs and HFs of HLA, including HLA-C and -DQB1, in Koreans by using high-resolution SBT. These data can be used to resolve ambiguous results of HLA typing for organ and hematopoietic stem cell transplantations.

Entities:  

Keywords:  Alleles; Frequency; HLA antigens; Haplotypes; Korea; Sequence analysis

Mesh：

Substances：

Year:  2015        PMID： 26131415      PMCID： PMC4446582          DOI： 10.3343/alm.2015.35.4.429

Source DB:  PubMed          Journal:  Ann Lab Med        ISSN： 2234-3806            Impact factor:   3.464


INTRODUCTION

Number of known alleles has rapidly increased because of the use of DNA-based HLA typing methods. Allele (AF) and haplotype frequencies (HF) of HLA are different among different ethnic groups and regions. In Koreans, AF and HF of HLA are reported by using generic DNA typing [1, 2, 3, 4] and high-resolution genotyping [5, 6, 7]. However, genotyping data for both of HLA-C and -DQB1 alleles using sequence-based typing (SBT) have not been obtained in previous studies, and some alleles such as C*07:01/*07:06 and DQB1*02:01/02:02 have not been discriminated [2, 3, 4, 5]. Recent studies have shown that HLA-C and -DQB1 matches are important for hematopoietic stem cell and organ transplantations [8, 9, 10, 11, 12]. Understanding the exact frequencies of HLA and other common, well-defined alleles in different ethnic groups is important to resolve ambiguous results of HLA typing. Higher AF of C*07:06 in the Chinese than in Caucasians was the cause of PCR dropout of widely used AlleleSEQR HLA-C Plus kit (Abbott Molecular, Des Plaines, IL, USA) because the kit was mainly developed for HLA typing for Caucasians [13]. The present study analyzed the AF and HF of HLA-A, -B, -C, -DRB1, and -DQB1 in Koreans by using high-resolution SBT and compared them with other ethnic groups.

METHODS

1. Subjects

Hematopoietic stem cells were obtained from 613 healthy Korean donors (559 healthy unrelated adults and 54 umbilical cord blood units) for high-resolution HLA typing at Seoul National University Hospital from January 2006 to July 2014. This study was approved by the Institutional Review Board (IRB) of Seoul National University Hospital (IRB No. 1408-028-601).

2. SBT analysis

Genomic DNA was extracted from white blood cells obtained from the peripheral blood of the donors and umbilical cord blood units by using QuickGene-Mini80 DNA isolation system (Fujifilm, Tokyo, Japan). SBT of HLA-A, -B, -C, -DRB1, and -DQB1 was performed by using AlleleSEQR HLA-A, -B, -C, -DRB1, and -DQB1 SBT kits (Abbott Molecular), respectively. For HLA class I alleles (HLA-A, -B, and -C), PCR mixture was prepared using 16 µL of master mix, 80-160 ng of genomic DNA, and 0.3 µL of AmpliTaq Gold polymerase (Abbott Molecular) at a final volume of 10 µL. For HLA class II alleles (HLA-DRB1 and -DQB1), PCR mixture was prepared by using 8 µL of master mix, 40-80 ng of genomic DNA, and 0.1 µL of AmpliTaq Gold polymerase at a final volume of 10 µL. Amplification conditions were as follows: initial denaturation at 95℃ for 10 min, followed by 36 cycles of denaturation at 96℃ for 20 sec, annealing at 60℃ for 30 sec, and elongation at 72℃ for 3 min. Next, 16 µL of the PCR products were mixed with 3 µL of ExoSAP-IT and were purified at 37℃ for 15-30 min and 80℃ for 15 min. Exons 2, 3, and 4 were sequenced for HLA class I alleles (HLA-A, -B, and -C); exon 2 and codon 86 were sequenced for HLA-DRB1; and exons 2 and 3 were sequenced for HLA-DQB1. Next, 8 µL of sequencing mix was added to 2 µL of the purified PCR products, and sequencing was performed by using 25 thermal cycles of denaturation at 96℃ for 20 sec, annealing at 50℃ for 30 sec, and elongation at 60℃ for 2 min. Next, 2 µL of sodium acetate/EDTA buffer and 25 µL of absolute ethanol (EtOH) were added to the mixture containing sequenced products. The mixture was then vigorously vortexed and centrifuged at 2,000g for 30 min, and the supernatant was removed. Next, 50 µL of 80% EtOH was added, and the mixture was centrifuged at 2,000g for 5 min; this process was repeated twice. Finally, 15 µL of highly deionized formamide (Applied Biosystems, Foster City, CA, USA) and 15 µL of 0.3 mM EDTA were added, and the mixture was loaded onto 3730xl DNA Analyzer (Applied Biosystems, Foster City, CA, USA). The obtained electropherograms were processed by using Assign SBT (Conexio Genomics, Fremantle Western Australia, Australia). To resolve ambiguity in C*07:01/07:06/07:18 group, exon 5 sequences of HLA-C were further analyzed, as described previously [14].

3. Statistical analysis

AFs and HFs of the HLA alleles were determined by using direct counting and maximum likelihood method, respectively. For 2-locus haplotypes, relative linkage disequilibrium (RLD) values between two alleles at different loci were analyzed and chi-square values were calculated for statistical significance. HFs of HLA A-C-B-DRB1-DQB1 haplotypes and AFs of HLA-C and -DQB1 in Koreans were compared with those in other populations by using chi-square test or Fisher's exact test, as appropriate. Bonferroni correction was applied by multiplying P values with the number of comparisons made (24 for HLA A-C-B-DRB1-DQB1 haplotypes, 24 for HLA-C, and 14 for HLA-DQB1) to calculate corrected P values (Pc). Pc value of <0.05 was considered significantly different. All analyses were performed by using R version 3.1.2 software with gap package (http://cran.us.r-project.org/) [15].

RESULTS

1. AFs of HLA -A, -B, -C, -DRB1, and -DQB1

AFs of HLA classes I and II are listed in Table 1. For the HLA-A locus, A2 group comprised more than 50% of all the HLA-A alleles. In all, 24 distinct alleles were identified for the HLA-A locus. Of these, A*24:02 was the most common allele, followed by A*02:01, A*33:03, A*02:06, and A*11:01 (AF ≥5%). The HLA-B locus showed the greatest diversity, with 46 alleles. Of these, B*51:01, B*15:01, and B*44:03 were the most common alleles, followed by B*58:01, B*35:01, B*54:01, and B*46:01 (AF ≥5%). In all, 24 alleles were identified for the HLA-C locus. Of these, C*01:02 was the most common allele, followed by C*03:03, C*03:04, C*14:02, C*03:02, C*07:02, C*08:01, C*06:02, and C*14:03 (AF ≥5%). AFs of C*07:01 and C*07:06 were 0.16% and 3.18%, respectively. In all, 29 alleles were identified for the HLA-DRB1 locus. Of these, DRB1*09:01 was the most common allele, followed by DRB1*13:02, DRB1*04:05, DRB1*15:01, DRB1*07:01, DRB1*08:03, and DRB1*01:01 (AF ≥5%). In all, 15 alleles were identified for the HLA-DQB1 locus. The sum of AFs of DQB1*03:01 and DQB1*03:03 were 25.2%. AFs of three DQ6 alleles (DQB1*06:01, DQB1*06:02, and DQB1*06:04), DQB1*02:02, DQB1*03:02, DQB1*04:01, and DQB1*05:01 were ≥5%. AFs of DQB1*02:01 and DQB1*02:02 were 2.12% and 6.69%, respectively.
Table 1

AFs (%) of HLA-A, -B, -C, -DRB1, and -DQB1 in Koreans (N=613)

AlleleAF (%)AlleleAF (%)AlleleAF (%)
A*01:011.88B*07:023.10DRB1*01:016.44
A*02:0117.62B*07:05†0.41DRB1*03:012.12
A*02:030.73B*08:010.33DRB1*04:010.98
A*02:069.46B*13:012.28DRB1*04:033.10
A*02:073.51B*13:024.16DRB1*04:041.96
A*02:100.33B*14:011.96DRB1*04:059.05
A*03:011.55B*15:018.73DRB1*04:064.16
A*03:020.08B*15:020.24DRB1*04:070.49
A*11:017.91B*15:071.47DRB1*04:101.39
A*11:020.49B*15:111.55DRB1*07:016.93
A*23:010.08B*15:170.08DRB1*08:021.96
A*24:0222.68B*15:181.06DRB1*08:036.61
A*24:080.08B*15:270.33DRB1*09:019.46
A*24:200.24B*15:380.16DRB1*10:011.96
A*26:012.61B*27:040.16DRB1*11:013.83
A*26:022.28B*27:053.10DRB1*11:060.08
A*26:030.82B*35:016.12DRB1*12:01‡4.40
A*29:010.33B*35:030.16DRB1*12:023.18
A*30:013.92B*35:310.08DRB1*13:011.63
A*30:042.12B*37:012.12DRB1*13:029.30
A*31:014.57B*38:010.08DRB1*13:070.08
A*32:010.57B*38:020.82DRB1*14:031.22
A*33:0316.07B*39:010.90DRB1*14:053.59
A*33:250.08B*40:013.83DRB1*14:060.73
B*40:024.24DRB1*14:070.08
C*01:0217.81B*40:030.57DRB1*14:542.45
C*01:030.08B*40:063.59DRB1*15:018.24
C*01:040.08B*40:730.08DRB1*15:023.75
C*02:020.49B*44:021.47DRB1*16:020.82
C*03:027.42B*44:038.16
C*03:0311.83B*46:015.06DQB1*02:012.12
C*03:048.97B*47:010.08DQB1*02:026.69
C*04:014.89B*48:013.91DQB1*03:0114.03
C*05:011.47B*50:010.08DQB1*03:029.62
C*06:026.36B*51:019.54DQB1*03:0311.17
C*07:010.16B*51:020.33DQB1*04:018.81
C*07:027.26B*52:012.85DQB1*04:023.92
C*07:040.90B*54:015.71DQB1*05:018.97
C*07:063.18B*55:021.31DQB1*05:022.12
C*08:016.93B*55:040.16DQB1*05:034.49
C*08:021.96B*55:070.08DQB1*06:019.38
C*08:030.98B*56:010.08DQB1*06:027.75
C*12:023.10B*57:010.08DQB1*06:031.63
C*12:030.33B*58:016.77DQB1*06:045.06
C*14:027.99B*59:011.71DQB1*06:094.24
C*14:035.14B*67:010.90
C*15:022.20
C*15:050.41
C*16:020.08

AFs of ≥5% are boldfaced.

†B and ‡DRB1 were not discriminated in the present study.

Abbreviation: AF, allele frequency.

2. HFs of HLA -A, -B, -C, -DRB1, and -DQB1

The 2-locus haplotypes exhibiting HFs higher than 0.9% are listed in Table 2. HFs of 31 A-C, 27 B-DRB1, 29 C-B, and 24 DRB1-DQB1 haplotypes were >0.9%. In each set, A*33:03-C*03:02, B*44:03-DRB1*13:02, C*14:02-B*51:01, and DRB1*09:01-DQB1*03:03 were the most common alleles. Three haplotypes (C*08:02-B*14:01, C*05:01-B*44:02, and DRB1*13:01-DQB1*06:03) showed the strongest associations with RLD values of >0.99. HFs (RLD, χ2) of A*33:03-C*07:06 and C*07:06-B*44:03 were 3.09% (0.40, 83.6) and 3.10% (0.59, 301.3), respectively, while those of DRB1*07:01-DQB1*02:02 and DRB1*03:01-DQB1*02:01 were 6.61% (0.97, 377.8) and 2.04% (0.96, 320.0), respectively. Table 3 lists 5-locus HLA A-C-B-DRB1-DQB1 haplotypes having HFs of >0.5%. The most common 5-locus haplotype was A*33:03-C*14:03-B*44:03-DRB1*13:02-DQB1*06:04, followed by A*33:03-C*03:02-B*58:01-DRB1*13:02-DQB1*06:09 (Table 3). HF of A*33:03-C*07:06-B*44:03-DRB1*07:01-DQB1*02:02 was 2.36%. HF of A*33:03-C*03:02-B*58:01-DRB1*13:02-DQB1*06:09 was higher while that of A*24:02-C*12:02-B*52:01-DRB1*15:02-DQB1*06:01 was lower than that in the Japanese (Pc<0.01) (Table 3).
Table 2

HFs (%) of two-locus HLA haplotypes in Koreans†

HaplotypeHF (%)RLDχ2HaplotypeHF (%)RLDχ2
A*33:03C*03:026.520.55162.3C*14:02B*51:017.990.91810.9
A*02:01C*01:025.850.1918.1C*03:02B*58:016.770.95892.4
A*33:03C*14:035.050.52136.9C*01:02B*54:015.620.52239.5
A*24:02C*01:024.140.010.0C*14:03B*44:035.050.77545.3
A*30:01C*06:023.750.74243.6C*01:02B*46:014.770.46210.1
A*24:02C*03:033.530.061.5C*06:02B*13:024.160.80561.7
A*24:02C*03:043.440.126.5C*03:03B*35:013.590.37132.8
A*33:03C*07:063.090.4083.6C*04:01B*15:013.340.48229.4
A*02:07C*01:022.820.3145.5C*07:06B*44:033.100.59301.3
A*02:01C*03:032.820.061.4C*03:03B*15:013.070.2255.5
A*24:02C*14:022.640.073.2C*03:04B*40:023.030.46163.0
A*24:02C*07:022.630.093.3C*07:02B*07:022.930.60351.8
A*24:02C*12:022.600.2638.6C*08:01B*40:062.820.54308.4
A*02:06C*01:022.060.030.6C*12:02B*52:012.770.93769.9
A*02:01C*03:042.010.040.5C*01:02B*27:052.410.2860.8
A*30:04C*08:021.960.96468.9C*08:01B*48:012.120.37153.7
A*02:06C*14:021.890.1413.0C*08:02B*14:011.961.00933.2
A*11:01C*04:011.750.2332.7C*06:02B*37:011.950.52277.1
A*11:01C*01:021.670.030.2C*03:04B*40:011.900.2872.4
A*02:06C*08:011.620.1310.5C*03:04B*13:011.850.38134.6
A*02:06C*03:031.460.040.6C*01:02B*59:011.710.2878.3
A*31:01C*14:021.430.1918.5C*03:03B*15:111.550.34115.2
A*01:01C*06:021.360.3769.0C*05:01B*44:021.471.00774.1
A*02:01C*08:011.310.010.0C*03:03B*15:071.380.31109.5
A*24:02C*08:011.27-0.030.5C*03:04B*40:061.080.1416.9
A*11:01C*07:021.220.093.9C*08:01B*35:011.020.107.8
A*02:01C*07:021.18-0.010.3C*01:02B*55:021.010.1828.0
A*02:01C*14:021.17-0.020.3C*08:03B*48:010.980.49204.0
A*26:01C*03:031.140.1616.5C*07:02B*67:010.900.3498.2
A*02:01C*06:021.00-0.010.4
A*24:02C*04:010.91-0.020.3DRB1*09:01DQB1*03:039.460.91360.9
DRB1*04:05DQB1*04:018.810.99384.4
B*44:03DRB1*13:024.750.50303.2DRB1*15:01DQB1*06:027.750.97359.6
B*58:01DRB1*13:023.830.44234.7DRB1*07:01DQB1*02:026.610.97377.8
B*13:02DRB1*07:013.650.66485.5DRB1*01:01DQB1*05:016.360.83263.0
B*46:01DRB1*08:033.540.59461.4DRB1*08:03DQB1*06:016.190.77227.6
B*15:01DRB1*04:062.940.46325.9DRB1*13:02DQB1*06:045.060.72223.0
B*54:01DRB1*04:052.920.36132.5DRB1*13:02DQB1*06:094.240.66170.9
B*07:02DRB1*01:012.850.63509.6DRB1*04:06DQB1*03:024.070.62172.4
B*44:03DRB1*07:012.790.32123.3DRB1*11:01DQB1*03:013.650.4780.7
B*52:01DRB1*15:022.770.84768.7DRB1*12:01‡DQB1*03:013.490.4059.7
B*27:05DRB1*01:012.590.57331.1DRB1*15:02DQB1*06:013.150.50100.1
B*40:06DRB1*09:012.090.32133.2DRB1*04:03DQB1*03:023.100.55125.4
B*37:01DRB1*10:011.960.961046.6DRB1*12:02DQB1*03:013.000.4263.0
B*13:01DRB1*12:021.950.72637.9DRB1*14:05DQB1*05:032.930.73201.0
B*58:01DRB1*03:011.780.45227.2DRB1*03:01DQB1*02:012.040.96320.0
B*51:01DRB1*09:011.570.087.3DRB1*10:01DQB1*05:011.960.4577.2
B*14:01DRB1*04:041.550.79627.8DRB1*04:04DQB1*04:021.710.61120.4
B*59:01DRB1*04:051.540.37132.2DRB1*13:01DQB1*06:031.631.00409.1
B*35:01DRB1*15:011.520.1531.0DRB1*14:54DQB1*05:031.350.3946.8
B*15:01DRB1*15:011.300.086.5DRB1*04:10DQB1*04:021.300.5588.0
B*54:01DRB1*15:011.300.1316.4DRB1*14:03DQB1*03:011.220.2825.9
B*15:07DRB1*04:031.220.56371.1DRB1*14:54DQB1*05:021.130.4872.5
B*15:01DRB1*04:051.220.051.9DRB1*08:02DQB1*03:020.980.1914.3
B*51:01DRB1*15:011.190.052.2
B*51:01DRB1*12:01‡1.070.1117.2
B*40:01DRB1*04:051.050.1313.2
B*40:02DRB1*09:011.050.1112.5
B*40:01DRB1*09:010.970.1111.8

Haplotypes with RLD values of ≥0.7 are boldfaced.

†Two-locus HLA haplotypes with HFs of >0.9% are listed; ‡DRB1 was not discriminated in the present study.

Abbreviations: HF, haplotype frequency; RLD, relative linkage disequilibrium.

Table 3

HFs (%) of five-locus HLA haplotypes in Koreans† and Japanese

HaplotypesHF (%)
A*C*B*DRB1*DQB1*Present studyKoreans [4]Japanese [16]
33:0314:0344:0313:0206:044.494.234.07
33:0303:0258:0113:0206:093.342.990.19∥
30:0106:0213:0207:0102:023.262.680.39§
24:0212:0252:0115:0206:012.441.927.17∥
33:0307:0644:0307:0102:022.362.99‡0.00§
02:0701:0246:0108:0306:012.280.821.55
24:0207:0207:0201:0105:012.162.892.71
02:0101:0227:0501:0105:011.761.13
30:0408:0214:0104:0404:021.551.24
11:0104:0115:0104:0603:021.481.241.74
33:0303:0258:0103:0102:011.471.85
24:0201:0254:0104:0504:011.430.621.94
01:0106:0237:0110:0105:011.131.030.39
24:0201:0259:0104:0504:011.001.130.97
24:0214:0251:0109:0103:030.98
02:0103:0413:0112:0203:010.880.930.58
02:0101:0254:0115:0106:020.76
11:0101:0254:0104:0504:010.730.931.16
24:0203:0315:0704:0303:020.730.19
02:0608:0140:0609:0103:030.65
03:0105:0144:0213:0106:030.650.39
24:0203:0413:0112:0203:010.59
24:0203:0440:0209:0103:030.570.78
33:0303:0258:0115:0106:020.57

†Five-locus HLA haplotypes with HFs of >0.5% are listed; ‡C was not discriminated in the present study; §Pc<0.05; ∥Pc<0.01.

Abbreviations: HF, haplotype frequency; Pc, corrected P value.

3. Comparison of AFs of HLA-C and -DQ with other ethnic groups

For the HLA-C locus, AFs of C*03:02 and C*07:01/06 were higher and that of C*12:02 was lower than those in the Japanese (Pc<0.001; Table 4). AF of C*03:03 was higher and that of C*07:02 was lower than that in the Chinese (Pc<0.001). AFs of C*01:02, C*03:02, C*08:01, C*14:02, and C*14:03 were higher and those of C*02:02, C*04:01, C*07:01/06, C*12:03, and C*16:01 were lower than those in Caucasians (Pc<0.001; Table 4). For the HLA-DQB1 locus, AF of DQB1*02:01/02 was higher and that of DQB1*06:01 was lower than that in the Japanese (Pc<0.001; Table 5). AF of DQB1*05:02 was lower than that in the Chinese (Pc<0.001). AFs of DQB1*04:01, *05:01, and *06:01 were higher and those of DQB1*02:01/02 and DQB1*06:02 were lower than those in Caucasians (Pc<0.001; Table 5).
Table 4

AFs (%) of HLA-C in Koreans, Japanese, Chinese, and Caucasians

SerologyHLA-C†Koreans‡ (N=613)Japanese [17] (N=371)Chinese [18] (N=264)Caucasians [19] (N=558)
1*01:0217.814.817.43.7**
*01:030.10.4
*01:040.1
2*02:020.55.8**
3 (10)*03:027.40.4**8.90.4**
3 (9)*03:0311.812.13.8**5.5
3 (10)*03:049.013.711.26.2
4*04:014.94.64.513.0**
5*05:011.50.45.6
6*06:026.41.6∥2.89.8
7*07:010.21.7§16.1§,**
*07:027.314.621.0**11.6
*07:040.90.90.92.0
*07:063.20.0**0.0∥
8*08:016.97.413.30.2**
*08:022.00.23.1
*08:031.02.00.1
Blank*12:023.110.5**1.70.8
*12:030.31.77.0**
*14:028.04.93.21.6**
*14:035.18.90.2∥0.0**
*15:022.22.73.81.9
*15:050.41.10.5
*16:012.8**
*16:020.10.4

†HLA-C alleles observed in the present study or having AFs of >1.0% in other populations were listed; ‡Present study; §C was not discriminated; ∥Pc<0.05; ¶Pc<0.01; **Pc<0.001.

Abbreviations: AF, allele frequency; Pc, corrected P value.

Table 5

AFs (%) of HLA-DQB1 in Korean, Japanese, Chinese, and Caucasian populations

SerologyDQB1†Korean‡ (N=613)Japanese [17] (N=371)Chinese [18] (N=264)Caucasian [20] (N=250)
2*02:012.10.3§,**12.1§26.6§,**
*02:026.7
3 (7)*03:0114.011.324.215.4
3 (8)*03:029.610.87.010.4
3 (9)*03:0311.213.515.06.8
4*04:018.811.54.00.0**
*04:023.93.90.80.8
5*05:019.07.53.40.2**
*05:022.13.511.0**0.8
*05:034.52.73.02.6
6*06:019.418.3**11.20.2**
*06:027.88.23.819.6**
*06:031.60.70.95.0
*06:045.17.30.8∥2.0
*06:094.20.41.90.2∥

†HLA-DQB1 alleles observed in the present study or having AFs of >1.0% in other populations were listed; ‡Present study; §DQB1 was not discriminated; ∥Pc<0.05; ¶Pc<0.01; **Pc<0.001.

Abbreviations: AF, allele frequency; Pc, corrected P value.

DISCUSSION

In this study, we investigated the distribution of AFs and HFs of five HLA loci (HLA-A, -B, -C, -DRB1, and -DQB1) in 613 healthy Korean hematopoietic stem cell donors by using high-resolution DNA typing. AFs of HLA-A, -B, -DRB1, and -DQB1 were similar to those reported in previous studies [1, 2, 3, 4, 5, 6, 7]. For the HLA-C locus, AF of C*03:02 (7.42%) was lower but that of C*03:04 (8.97%) was higher than that determined by using PCR-sequence specific oligonucleotides (PCR-SSO) and sequencing in a previous study involving 485 healthy Koreans (10.82% for C*03:02 and 3.82% for C*03:04) [4]. However, AFs reported in our study were similar to those obtained by using PCR-SSO and sequence-specific conformational polymorphism in another study involving 474 healthy Koreans (6.3% for C*03:02 and 9.9% for C*03:04) [5]. This discrepancy should be clarified in further studies by performing high-resolution DNA typing in a larger study population. Compared with the previous two studies [4, 5], we further discriminated HLA-C*07:01/*07:06 and determined AFs of C*07:01 (0.16%) and C*07:06 (3.18%) and HFs of A*33:03-C*07:06 (3.09%) and C*07:06-B*44:03 (3.10%), with significant χ2 values (83.6 and 301.3, respectively). Strong linkage disequilibrium of C*07:06 with A*33:03 or B*44:03 observed in the present study was in accordance with that reported in a previous study involving 118 healthy Koreans [14]. Therefore, most A*33:03-C*07:01/06 and C*07:01/06-B*44:03 haplotypes reported previously [4, 5] would be A*33:03-C*07:06 and C*07:06-B*44:03 [4, 5]. Further, we discriminated DQB1*02:01/*02:02 and determined AFs of DQB1*02:01 (2.12%) and DQB1*02:02 (6.69%) and HFs of DRB1*03:01-DQB1*02:01 (2.04%) and DRB1*07:01-DQB1*02:02 (6.61%), with significant χ2 values (320.0 and 377.8, respectively), which were similar to those reported in a previous study involving 414 parents of 207 Korean families [2]. For the 5-locus haplotypes, the results of the present study implied that most A*33:03-C*07:01/06-B*44:03-DRB1*07:01-DQB1*02:01/02 haplotype reported previously, with HF of 2.99% [4], would be A*33:03-C*07:06-B*44:03-DRB1*07:01-DQB1*02:02. In the present study, all the DQB1 alleles had AFs of >1.5%, with no additional DQB1 allele, compared with those reported in previous studies [2, 4], indicating lower polymorphism of the HLA-DQB1 locus in Koreans. Thus, for organ transplantation, HLA-DQB1 alleles might be analyzed by using an intermediate resolution typing kit to determine compatible donors or to define donor-specific HLA antibody. AFs of HLA-C alleles in different ethnic groups are listed in Table 4. From the perspective of killer cell immunoglobulin-like receptor (KIR) ligand status, the portion of HLA-C1 group (HLA-C alleles expressing Asn80, such as HLA-Cw1, -Cw3, -Cw7, -Cw8, -Cw12, -Cw13, -Cw14, and -Cw16) [21] was higher in Koreans than in Caucasians (84.2% vs. 61.1%). The portion of C2 group (HLA-C alleles expressing Lys80, such as HLA-Cw2, -Cw4, -Cw5, -Cw6, -Cw15, -Cw17, and -Cw18) was lower in Koreans than in Caucasians (15.8% vs. 36.6%). These differences could affect the frequency of KIR ligand mismatch for hematopoietic stem cell transplantation and possibly the clinical outcome. AFs of HLA-DQB1 alleles in different ethnic groups are listed in Table 5. AF of DQB1*06:01 was higher in Koreans (9.4%) than in Caucasians (0.2%), which might cause false reaction while using commercial kits developed in the United States [22]. In summary, we determined the AFs and HFs of HLA-A, -B, -C, -DRB1, and -DQB1 in Koreans by using high-resolution SBT. These data could be used to determine exact HLA types in Koreans for organ and hematopoietic stem cell transplantations.
  18 in total

1.  HLA class I (A, B, C) and class II (DRB1, DQA1, DQB1, DPB1) alleles and haplotypes in the Han from southern China.

Authors:  E Trachtenberg; M Vinson; E Hayes; Y-M Hsu; K Houtchens; H Erlich; W Klitz; Y Hsia; J Hollenbach
Journal:  Tissue Antigens       Date:  2007-09-27

Review 2.  Natural killer cell alloreactivity in allogeneic hematopoietic transplantation.

Authors:  Loredana Ruggeri; Antonella Mancusi; Emanuela Burchielli; Franco Aversa; Massimo F Martelli; Andrea Velardi
Journal:  Curr Opin Oncol       Date:  2007-03       Impact factor: 3.645

3.  [Allelic and haplotypic diversity of HLA-A, -B, -C, and -DRB1 genes in Koreans defined by high-resolution DNA typing].

Authors:  Hye Yoon Chung; Jung Ah Yoon; Bok Youn Han; Eun Yung Song; Myoung Hee Park
Journal:  Korean J Lab Med       Date:  2010-12

4.  HLA-A, -B, -DRB1 allele frequencies and haplotypic association from DNA typing data of 7096 Korean cord blood units.

Authors:  J H Yoon; S Shin; M H Park; E Y Song; E Y Roh
Journal:  Tissue Antigens       Date:  2010-02

5.  Risk of antibody-mediated rejection in kidney transplant recipients with anti-HLA-C donor-specific antibodies.

Authors:  O Aubert; M-C Bories; C Suberbielle; R Snanoudj; D Anglicheau; M Rabant; F Martinez; A Scemla; C Legendre; R Sberro-Soussan
Journal:  Am J Transplant       Date:  2014-05-07       Impact factor: 8.086

6.  High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation.

Authors:  Stephanie J Lee; John Klein; Michael Haagenson; Lee Ann Baxter-Lowe; Dennis L Confer; Mary Eapen; Marcelo Fernandez-Vina; Neal Flomenberg; Mary Horowitz; Carolyn K Hurley; Harriet Noreen; Machteld Oudshoorn; Effie Petersdorf; Michelle Setterholm; Stephen Spellman; Daniel Weisdorf; Thomas M Williams; Claudio Anasetti
Journal:  Blood       Date:  2007-09-04       Impact factor: 22.113

7.  Clinical significance of donor-recipient HLA matching on survival after myeloablative hematopoietic cell transplantation from unrelated donors.

Authors:  E W Petersdorf; T Gooley; M Malkki; M Horowitz
Journal:  Tissue Antigens       Date:  2007-04

8.  HLA-A, -B and -DRB1 polymorphism in Koreans defined by sequence-based typing of 4128 cord blood units.

Authors:  J Y Huh; D Y Yi; S-H Eo; H Cho; M H Park; M S Kang
Journal:  Int J Immunogenet       Date:  2013-05-31       Impact factor: 1.466

Review 9.  HLA-C Incompatibilities in Allogeneic Unrelated Hematopoietic Stem Cell Transplantation.

Authors:  Jean-Marie Tiercy
Journal:  Front Immunol       Date:  2014-05-19       Impact factor: 7.561

10.  Performance of LIFECODES HLA-DQB1 typing kit using Luminex platform in Koreans.

Authors:  Eun Youn Roh; Ji Won In; Sue Shin; Jong Hyun Yoon; Kyoung Un Park; Eun Young Song
Journal:  Ann Lab Med       Date:  2014-12-08       Impact factor: 3.464
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Authors:  Hyeyoung Lee; Ji Won Min; Hyunhye Kang; Hanbi Lee; Sang Hun Eum; Yohan Park; Chul Woo Yang; Byung Ha Chung; Eun-Jee Oh
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3.  [Clinical significance of HLA-A, -B, -C, -DRB1, -DQB1 haplotype gene frequencies].

Authors:  L Y Chen; Y Li; T T Zhang; X J Bao; X N Yuan; Y Li; L J Li; T J Yang; J He
Journal:  Zhonghua Xue Ye Xue Za Zhi       Date:  2019-12-14

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Journal:  Transl Clin Pharmacol       Date:  2019-06-28

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Authors:  Tran Thu Ha Pham; Quang Binh Tran; Chonlaphat Sukasem; Van Dinh Nguyen; Chi Hieu Chu; Thi Quynh Nga Do; Ngoc Phuong Mai Tran; Thanh Huong Phung
Journal:  Appl Clin Genet       Date:  2021-02-09

6.  Identification of 8-Digit HLA-A, -B, -C, and -DRB1 Allele and Haplotype Frequencies in Koreans Using the One Lambda AllType Next-Generation Sequencing Kit.

Authors:  Wonho Choe; Jeong-Don Chae; John Jeongseok Yang; Sang-Hyun Hwang; Sung-Eun Choi; Heung-Bum Oh
Journal:  Ann Lab Med       Date:  2021-05-01       Impact factor: 3.464

7.  Reducing severe cutaneous adverse and type B adverse drug reactions using pre-stored human leukocyte antigen genotypes.

Authors:  Kye Hwa Lee; Dong Yoon Kang; Hyun Hwa Kim; Yi Jun Kim; Hyo Jung Kim; Ju Han Kim; Eun Young Song; James Yun; Hye-Ryun Kang
Journal:  Clin Transl Allergy       Date:  2022-01-14       Impact factor: 5.871

8.  Association of human leukocyte antigen class II alleles with severe Middle East respiratory syndrome-coronavirus infection.

Authors:  Ali H Hajeer; Hanan Balkhy; Sameera Johani; Mohammed Z Yousef; Yaseen Arabi
Journal:  Ann Thorac Med       Date:  2016 Jul-Sep       Impact factor: 2.219

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Authors:  In-Cheol Baek; Eun-Jeong Choi; Dong-Hwan Shin; Hyoung-Jae Kim; Haeyoun Choi; Tai-Gyu Kim
Journal:  PLoS One       Date:  2021-06-21       Impact factor: 3.240

10.  Association of HLA-DRB1 and -DQB1 Alleles with Susceptibility to IgA Nephropathy in Korean Patients.

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  10 in total

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