KIR gene presence/absence polymorphisms and global diversity in the Kirgiz ethnic minority and populations distributed worldwide

  • Hong-Dan Wang
  • Xiao-Ye Jin
  • Yu-Xin Guo
  • Qian Zhang
  • Yu-Wei Zhang
  • Xin Wang
  • Bo-Feng ZhuEmail author
Original Article


Killer cell immunoglobulin like receptor genes expressed by the natural killer cells and T cells of some subclasses are one of the very diversity and complex gene families on chromosome 19q13.4 which play key developmental role in the fight against viral infections, malignantly transformed cells and so on in the first line. As potential markers, KIRs have received more and more attention for some infections and diseases which have some clinical outcomes. In addition, the KIRs are diverse in different populations due to the distinctive alleles and haplotypes, may contribute to understand the genetic relationships among populations. To data, there is no report on the KIR gene polymorphism of the Kirgiz ethnic minority. The purpose of this paper is to determine the KIR gene diversity: KIR gene presence/absence polymorphisms, haplotype/genotype polymorphisms and these polymorphisms between populations distributed worldwide. In this study, we have genotyped the 19 KIR genes: KIR2DL1-4, 2DL5A, 2DL5B, 2DS1-3, 2DS4*FUL, 2DS4*DEL, 2DS5, 3DL1-3, 3DS1, 2DP1, 3DP1*FUL and 3DP1*DEL, and two unique genotypes are found in two Kirgiz individuals. The PCA plot, Neighbor-Joining tree analysis and MDS plot are conducted and the groups of the same language family gather together basically. KIR gene diversity study of populations distributed in different parts of the world. shows that KIRs can be used as a supplement for human genetic researches.


Killer cell immunoglobulin-like receptors (KIRs) Genetic diversity PCR-SSP Kirgiz ethnic minority 



The present study was supported by the National Natural Science Foundation of China (Grant Nos. 81501336 and 81525015) and the Science and Technology Research Project of Henan Province (Grant No. 172102310295).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Becker PS, Suck G, Nowakowska P, Ullrich E, Seifried E, Bader P, Tonn T, Seidl C (2016) Selection and expansion of natural killer cells for NK cell-based immunotherapy. Cancer Immunol Immunother 65(4):477–484CrossRefGoogle Scholar
  2. 2.
    Parham P (2005) MHC class I molecules and KIRs in human history, health and survival. Nat Rev Immunol 5(3):201–214CrossRefGoogle Scholar
  3. 3.
    Jamil KM, Khakoo SI (2011) KIR/HLA interactions and pathogen immunity. J Biomed Biotechnol 2011:298348CrossRefGoogle Scholar
  4. 4.
    Norman PJ, Hollenbach JA, Nemat-Gorgani N, Marin WM, Norberg SJ, Ashouri E, Jayaraman J, Wroblewski EE, Trowsdale J, Rajalingam R, Oksenberg JR, Chiaroni J, Guethlein LA, Traherne JA, Ronaghi M, Parham P (2016) Defining KIR and HLA Class I genotypes at highest resolution via high-throughput sequencing. Am J Hum Genet 99(2):375–391CrossRefGoogle Scholar
  5. 5.
    Carrington M, Cullen M (2004) Justified chauvinism: advances in defining meiotic recombination through sperm typing. Trends Genet 20(4):196–205CrossRefGoogle Scholar
  6. 6.
    Canavez F, Young NT, Guethlein LA, Rajalingam R, Khakoo SI, Shum BP, Parham P (2001) Comparison of chimpanzee and human leukocyte Ig-like receptor genes reveals framework and rapidly evolving genes. J Immunol 167(10):5786–5794CrossRefGoogle Scholar
  7. 7.
    Jamali E, Barani S, Yousefinejad F, Ariafar A, Talei GR, Ghaderi A (2018) KIRs gene content diversity in Iranians with urothelial bladder cancer. Mol Biol Rep 45(5):713–719CrossRefGoogle Scholar
  8. 8.
    Olcese L, Cambiaggi A, Semenzato G, Bottino C, Moretta A, Vivier E (1997) Human killer cell activatory receptors for MHC class I molecules are included in a multimeric complex expressed by natural killer cells. J Immunol 158:5083–5086PubMedGoogle Scholar
  9. 9.
    Kikuchi-Maki A, Catina TL, Campbell KS (2005) Cutting edge: KIR2DL4 transduces signals into human NK cells through association with the Fc receptor gamma protein. J Immunol 174(7):3859–3863CrossRefGoogle Scholar
  10. 10.
    Marsh SG, Parham P, Dupont B, Geraghty DE, Trowsdale J, Middleton D, Vilches C, Carrington M, Witt C, Guethlein LA, Shilling H, Garcia CA, Hsu KC, Wain H (2003) Killer-cell immunoglobulin-like receptor (KIR) nomenclature report, 2002. Tissue Antigens 62(1):79–86CrossRefGoogle Scholar
  11. 11.
  12. 12.
    Pyo CW, Wang R, Vu Q, Cereb N, Yang SY, Duh FM, Wolinsky S, Martin MP, Carrington M, Geraghty DE (2013) Recombinant structures expand and contract inter and intragenic diversification at the KIR locus. BMC Genom 14:89CrossRefGoogle Scholar
  13. 13.
    Pyo CW, Guethlein LA, Vu Q, Wang R, Abi-Rached L, Norman PJ, Marsh SG, Miller JS, Parham P, Geraghty DE (2010) Different patterns of evolution in the centromeric and telomeric regions of group A and B haplotypes of the human killer cell Ig-like receptor locus. PLoS ONE 5(12):e15115CrossRefGoogle Scholar
  14. 14.
    Uhrberg M, Parham P, Wernet P (2002) Definition of gene content for nine common group B haplotypes of the Caucasoid population: KIR haplotypes contain between seven and eleven KIR genes. Immunogenetics 54(4):221–229CrossRefGoogle Scholar
  15. 15.
    Norman PJ, Carrington CV, Byng M, Maxwell LD, Curran MD, Stephens HA, Chandanayingyong D, Verity DH, Hameed K, Ramdath DD, Vaughan RW (2002) Natural killer cell immunoglobulin-like receptor (KIR) locus profiles in African and South Asian populations. Genes Immun 3(2):86–95CrossRefGoogle Scholar
  16. 16.
    Wang HD, Feng ZQ, Shen CM, Guo QN, Dai PF, Zhang YD, Guo YX, Yan JW, Zhu BF, Zhang L (2016) Study of genetic diversity of killer cell immunoglobulin-like receptor loci in the Tujia ethnic minority. Hum Immunol 77(10):869–875CrossRefGoogle Scholar
  17. 17.
    Zhang L, Hsu KC, Liu XR, Yang JQ, Yao FJ, Xu LD, Dupont B, Fan LA (2003) Killer Ig-like receptor gene content diversity and haplotype analysis in Chinese Han population in Shanghai. Chin J Med Genet 20(5):396–399Google Scholar
  18. 18.
    Yawata M, Yawata N, Mcqueen KL, Cheng NW, Guethlein LA, Rajalingam R, Shilling HG, Parham P (2002) Predominance of group A KIR haplotypes in Japanese associated with diverse NK cell repertoires of KIR expression. Immunogenetics 54(8):543–550CrossRefGoogle Scholar
  19. 19.
    Yao Y, Shi L, Tao Y, Lin K, Liu S, Yu L, Yang Z, Yi W, Huang X, Sun H (2011) Diversity of killer cell immunoglobulin-like receptor genes in four ethnic groups in China. Immunogenetics 63(8):475–483CrossRefGoogle Scholar
  20. 20.
    Wang HD, Zhu BF, Shen CM, Yuan GL, Yang G, Guo JN, Yan JW, Qin HX, Guo JX, Zhang LP (2012) Genetic polymorphism analysis of killer cell immunoglobulin-like receptor genes in the Chinese Uygur population. Mol Biol Rep 39(3):3017CrossRefGoogle Scholar
  21. 21.
    Wang HD, Zhu BF, Shen CM, Fan AY, Song TN, Liu JL, Qin HX, Deng LB, Fan SL, Huang QZ (2011) Diversity distributions of killer cell immunoglobulin-like receptor genes and their ligands in the Chinese Shaanxi Han population. Hum Immunol 72(9):733CrossRefGoogle Scholar
  22. 22.
    Wang HD, Zhang FX, Shen CM, Wu YM, Lv YG, Xie ST, Yang G, Qin HX, Fan SL, Zhu BF (2012) The distribution of genetic diversity of KIR genes in the Chinese Mongolian population. Hum Immunol 73(10):1031CrossRefGoogle Scholar
  23. 23.
    Su PC, Yang TH, Zou H, Xu XH, Li YM, Zhu XM, Gao H, Zheng ZW, Chen Q (2008) Polymorphism of killer cell immunoglobulin-like receptors gene in Yunnan Han population, China. Chin J Blood Transfus 4:268–272Google Scholar
  24. 24.
    Li PD, Zheng DH, Chang W, Liu JH, Jing FS, Hai JJ, Gao CJ, Li Y, Wan MD (2008) The diversity of KIR gene in Chinese Northern Han population and the impact of donor KIR and patient HLA genotypes on outcome following HLA-identical sibling allogeneic hematopoietic stem cell transplantation for hematological malignancy in Chinese people. Int J Hematol 87(4):422–433CrossRefGoogle Scholar
  25. 25.
    Jiang K, Zhu FM, Lv QF, Yan LX (2005) Distribution of killer cell immunoglobulin-like receptor genes in the Chinese Han population. Tissue Antigens 65(6):556CrossRefGoogle Scholar
  26. 26.
    Yi CL, Chan SH, Ren EC (2008) Asian population frequencies and haplotype distribution of killer cell immunoglobulin-like receptor (KIR) genes among Chinese, Malay, and Indian in Singapore. Immunogenetics 60(11):645–654CrossRefGoogle Scholar
  27. 27.
    Whang DH, Park H, Yoon JA, Park MH (2005) Haplotype analysis of killer cell immunoglobulin-like receptor genes in 77 Korean families. Hum Immunol 66(2):146–154CrossRefGoogle Scholar
  28. 28.
    Chi YB, Lei Z, Yang JQ, Yao FJ, Ling-Di XU, Fan LA (2005) The diversity of KIR gene content and haplotype analysis in Xinjiang Uygur and Yunnan Yi populations in China. Immunology 25:204–207Google Scholar
  29. 29.
    Tamura K, Stecher G, Peterson D, Filipski A, Kumar S (2013) MEGA6: molecular evolutionary genetics analysis version 6.0. Mol Biol Evol 30:2725–2729CrossRefGoogle Scholar
  30. 30.
    Excoffier L, Lischer HE (2010) Arlequin suite ver 3.5: a new series of programs to perform population genetics analyses under Linux and Windows. Mol Ecol Resour 10:564–567CrossRefGoogle Scholar
  31. 31.
    Erken E, Goruroglu Ozturk O, Kudas O, Arslan Tas D, Demirtas A, Kibar F, Dinkci S, Erken E (2015) Killer cell immunoglobulin-like receptor (KIR) genotype distribution in familial mediterranean fever (FMF) Patients. Med Sci Monit 17:21:3547–3554CrossRefGoogle Scholar
  32. 32.
    Long EO, Rajagopalan S (2000) HLA class I recognition by killer cell Ig-like receptors. Semin Immunol 12(2):101–108CrossRefGoogle Scholar
  33. 33.
    Uhrberg M, Valiante NM, Young NT, Lanier LL, Phillips JH, Parham P (2001) The repertoire of killer cell Ig-like receptor and CD94:NKG2A receptors in T cells: clones sharing identical alpha beta TCR rearrangement express highly diverse killer cell Ig-like receptor patterns. J Immunol 166(6):3923–3932CrossRefGoogle Scholar
  34. 34.
    Thomas R, Yamada E, Alter G, Martin MP, Bashirova AA, Norman PJ, Altfeld M, Parham P, Anderson SK, McVicar DW, Carrington M (2008) Novel KIR3DL1 alleles and their expression levels on NK cells: convergent evolution of KIR3DL1 phenotype variation? J Immunol 180(10):6743–6750CrossRefGoogle Scholar
  35. 35.
    Parham P, Abi-Rached L, Matevosyan L, Moesta AK, Norman PJ, Older Aguilar AM, Guethlein LA (2010) Primate-specific regulation of natural killer cells. J Med Primatol 39(4):194–212CrossRefGoogle Scholar
  36. 36.
    Wang T, Shen C, Chen L, Liu S, Ji Y (2017) Association of human leukocyte antigen polymorphisms with occult hepatitis B virus infection in a Shaanxi Han population. J Gene Med 19:9–10Google Scholar
  37. 37.
    Hagenlocher Y, Willburger B, Behrens GA, Schmidt AH, Ioffe Y, Sauter J (2018) 6-locus HLA allele and haplotype frequencies in a population of 1075 Russians from Karelia. Hum Immunol. CrossRefPubMedGoogle Scholar
  38. 38.
    Single RM, Martin MP, Gao X, Meyer D, Yeager M, Kidd JR, Kidd KK, Carrington M (2007) Global diversity and evidence for coevolution of KIR and HLA. Nat Genet 39(9):1114–1119CrossRefGoogle Scholar
  39. 39.
    Augusto DG, Petzl-Erler ML (2015) KIR and HLA under pressure: evidences of coevolution across worldwide populations. Hum Genet 134(9):929 – 40.40CrossRefGoogle Scholar
  40. 40.
    Heatley SL, Mullighan CG, Doherty K, Danner S, O’Connor GM, Hahn U, Szer J, Schwarer A, Bradstock K, Sullivan LC, Bardy PG, Brooks AG (2018) Activating KIR haplotype influences clinical outcome following HLA-matched sibling hematopoietic stem cell transplantation. HLA. CrossRefPubMedGoogle Scholar
  41. 41.
    Sahin U, Dalva K, Gungor F, Ustun C, Beksac M (2018) Donor-recipient killer immunoglobulin like receptor (KIR) genotype matching has a protective effect on chronic graft versus host disease and relapse incidence following HLA-identical sibling hematopoietic stem cell transplantation. Ann Hematol 97(6):1027–1039CrossRefGoogle Scholar
  42. 42.
    Boudreau JE, Hsu KC (2018) Natural killer cell education in human health and disease. Curr Opin Immunol 50:102–111CrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Hong-Dan Wang
    • 1
    • 2
  • Xiao-Ye Jin
    • 1
  • Yu-Xin Guo
    • 1
  • Qian Zhang
    • 2
  • Yu-Wei Zhang
    • 2
  • Xin Wang
    • 2
  • Bo-Feng Zhu
    • 1
    Email author
  1. 1.Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of StomatologyXi’an Jiaotong UniversityXi’anPeople’s Republic of China
  2. 2.Medical Genetic Institute of Henan Province, Henan Provincial People’s HospitalPeople’s Hospital of Zhengzhou UniversityZhengzhouPeople’s Republic of China

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