Ann Lab Med.  2015 Jul;35(4):429-435. 10.3343/alm.2015.35.4.429.

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

• In JW
• Roh EY
• Oh S
• Shin S
• Park KU
• Song EY

• KMID: 2045866
• DOI: http://doi.org/10.3343/alm.2015.35.4.429

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 > or =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 > or =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.

Keyword

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

MeSH Terms

Alleles*
DNA Fingerprinting*
Gene Frequency
Genotype
Haplotypes*
Hematopoietic Stem Cells
Histocompatibility Testing
HLA Antigens
HLA-A Antigens
HLA-B Antigens
HLA-C Antigens
HLA-DRB1 Chains
Humans
Korea
Leukocytes*
Sequence Analysis
Unrelated Donors
HLA Antigens
HLA-A Antigens
HLA-B Antigens
HLA-C Antigens
HLA-DRB1 Chains

Reference

1. Roh EY, Kim HS, Kim SM, Lim YM, Han BY, Park MH. HLA-A, -B, -DR allele frequencies and haplotypic associations in Koreans defined by generic-level DNA typing. Korean J Lab Med. 2003; 23:420–430.

2. Song EY, Park MH, Kang SJ, Park HJ, Kim BC, Tokunaga K, et al. HLA class II allele and haplotype frequencies in Koreans based on 107 families. Tissue Antigens. 2002; 59:475–486. PMID: 12445317.

3. Hwang SH, Oh HB, Yang JH, Kwon OJ, Shin ES. Distribution of HLA-A, B, C allele and haplotype frequencies in Koreans. Korean J Lab Med. 2004; 24:396–404.

4. Lee KW, Oh DH, Lee C, Yang SY. Allelic and haplotypic diversity of HLA-A, -B, -C, -DRB1, and -DQB1 genes in the Korean population. Tissue Antigens. 2005; 65:437–447. PMID: 15853898.

5. Chung HY, Yoon JA, Han BY, Song EY, Park MH. Allelic and haplotypic diversity of HLA-A, -B, -C, and -DRB1 genes in Koreans defined by high-resolution DNA typing. Korean J Lab Med. 2010; 30:685–696. PMID: 21157157.

6. Huh JY, Yi DY, Eo SH, Cho H, Park MH, Kang MS. HLA-A, -B and -DRB1 polymorphism in Koreans defined by sequence-based typing of 4128 cord blood units. Int J Immunogenet. 2013; 40:515–523. PMID: 23724919.

7. Yoon JH, Shin S, Park MH, Song EY, Roh EY. HLA-A, -B, -DRB1 allele frequencies and haplotypic association from DNA typing data of 7096 Korean cord blood units. Tissue Antigens. 2010; 75:170–173. PMID: 20196826.

8. Petersdorf EW, Gooley T, Malkki M, Horowitz M. International Histocompatibility Working Group in Hematopoietic Cell Transplantation. Clinical significance of donor-recipient HLA matching on survival after myeloablative hematopoietic cell transplantation from unrelated donors. Tissue Antigens. 2007; 69(Suppl 1):25–30. PMID: 17445158.

9. Lee SJ, Klein J, Haagenson M, Baxter-Lowe LA, Confer DL, Eapen M, et al. High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation. Blood. 2007; 110:4576–4583. PMID: 17785583.

10. Tiercy JM. HLA-C incompatibilities in allogeneic unrelated hematopoietic stem cell transplantation. Front Immunol. 2014; 5:216. PMID: 24904572.

11. Aubert O, Bories MC, Suberbielle C, Snanoudj R, Anglicheau D, Rabant M, et al. , Risk of antibody-mediated rejection in kidney transplant recipients with anti-HLA-C donor-specific antibodies. Am J Transplant. 2014; 14:1439–1445. PMID: 24804568.

12. Willicombe M, Brookes P, Sergeant R, Santos-Nunez E, Steggar C, Galliford J, et al. De novo DQ donor-specific antibodies are associated with a significant risk of antibody-mediated rejection and transplant glomerulopathy. Transplantation. 2012; 94:172–177. PMID: 22735711.

13. Deng Z, Wang D, Xu Y, Gao S, Zhou H, Yu Q, et al. HLA-C polymorphisms and PCR dropout in exons 2 and 3 of the Cw*0706 allele in sequence-based typing for unrelated Chinese marrow donors. Hum Immunol. 2010; 71:577–581. PMID: 20226825.

14. Lee KW, Jung YA. Refined information on alleles belonging to the C*07:01/07:06/07:18 group in the Korean population. Human Immunol. 2011; 72:723–726. PMID: 21663780.

15. The Comprehensive R Archive Network. Updated on Oct 2014. http://cran.us.r-project.org/.

16. Nakajima F, Nakamura J, Yokota T. Analysis of HLA haplotypes in Japanese, using high resolution allele typing. MHC. 2001; 8:1–32.

17. Saito S, Ota S, Yamada E, Inoko H, Ota M. Allele frequencies and haplotypic associations defined by allelic DNA typing at HLA class I and class II loci in the Japanese population. Tissue Antigens. 2000; 56:522–529. PMID: 11169242.

18. Trachtenberg E, Vinson M, Hayes E, Hsu YM, Houtchens K, Erlich H, et al. HLA class I (A, B, C) and class II (DRB1, DQA1, DQB1, DPB1) alleles and haplotypes in the Han from southern China. Tissue Antigens. 2007; 70:455–463. PMID: 17900288.

19. Mack SJ, Tu B, Lazaro A, Yang R, Lancaster AK, Cao K, et al. HLA-A, -B, -C, and -DRB1 allele and haplotype frequencies distinguish Eastern European Americans from the general European American population. Tissue Antigens. 2009; 73:17–32. PMID: 19000140.

20. Dunne C, Crowley J, Hagan R, Rooney G, Lawlor E. HLA-A, B, Cw, DRB1, DQB1 and DPB1 alleles and haplotypes in the genetically homogenous Irish population. Int J Immunogenet. 2008; 35:295–302. PMID: 18976432.

21. Ruggeri L, Mancusi A, Burchielli E, Aversa F, Martelli MF, Velardi A. Natural killer cell alloreactivity in allogeneic hematopoietic transplantation. Curr Opin Oncol. 2007; 19:142–147. PMID: 17272987.

22. Roh EY, In JW, Shin S, Yoon JH, Park KU, Song EY. Performance of LIFECODES HLA-DQB1 typing kit using Luminex platform in Koreans. Ann Lab Med. 2015; 35:123–127. PMID: 25553292.