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Killer cell immunoglobulin-like receptor gene diversity in the Saudi population

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Abstract

Killer cell immunoglobulin-like receptors (KIRs) influence the outcome of haematopoetic stem cell transplantation by modulating the cytotoxic ability of natural killer (NK) cells and a subset of T cells. KIRs are also highly polymorphic and could therefore be good population genetic markers, much like their human leukocyte antigen (HLA) ligands. This study represents the first report on distribution of 16 KIR genes in 162 unrelated healthy Saudi individuals. All the 16 KIR genes were observed in the studied population and the four framework genes (KIR2DL4, 3DL2, 3DL3 and 3DP1) were present in all individuals. Forty- one distinct KIR profiles were expressed in our population, 11 of which had not been previously described in other populations including the Middle Eastern population. AA1, the most common genotypic profile was observed at a frequency of 26.5%. The group A haplotype was more frequent (53%) in the Saudi population compared to the group B haplotype (47%). The pattern of the inhibitory KIR/HLA ligands were also analyzed and 52.3% of the Saudi population was found to express two pairs of the inhibitory KIR/HLA-C. The KIR gene frequencies suggests that the Saudi population shares common general features with the Middle Eastern and other populations, but still has its own unique frequencies of several KIR loci.

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References

  1. Lanier LL (2005) NK cell recognition. Annu Rev Immunol 23:225–274

    Article  PubMed  CAS  Google Scholar 

  2. Vilches C, Parham P (2002) KIR: diverse, rapidly evolving receptors of innate and adaptive immunity. Annu Rev Immunol 20:217–251

    Article  PubMed  CAS  Google Scholar 

  3. 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 166:3923–3932

    PubMed  CAS  Google Scholar 

  4. Faure M, Long EO (2002) KIR2DL4 (CD158d), an NK cell-activating receptor with inhibitory potential. J Immunol 168:6208–6214

    PubMed  CAS  Google Scholar 

  5. Hsu KC, Chida S, Geraghty DE, Dupont B (2002) The killer cell immunoglobulin-like receptor (KIR) genomic region: gene-order, haplotypes and allelic polymorphism. Immunol Rev 190:40–52

    Article  PubMed  CAS  Google Scholar 

  6. 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 54:543–550

    Article  PubMed  Google Scholar 

  7. Uhrberg M, Valiante NM, Shum BP, Shilling HG, Lienert-Weidenbach K, Corliss B, Tyan D, Lanier LL, Parham P (1997) Human diversity in killer cell inhibitory receptor genes. Immunity 7:753–763

    Article  PubMed  CAS  Google Scholar 

  8. Yawata M, Yawata N, Abi-Rached L, Parham P (2002) Variation within the human killer cell immunoglobulin-like receptor (KIR) gene family. Crit Rev Immunol 22:463–482

    PubMed  CAS  Google Scholar 

  9. Hsu KC, Liu XR, Selvakumar A, Mickelson E, O’Reilly RJ, Dupont B (2002) Killer Ig-like receptor haplotype analysis by gene content: evidence for genomic diversity with a minimum of six basic framework haplotypes, each with multiple subsets. J Immunol 169:5118–5129

    PubMed  Google Scholar 

  10. Norman PJ, Stephens HA, Verity DH, Chandanayingyong D, Vaughan RW (2001) Distribution of natural killer cell immunoglobulin-like receptor sequences in three ethnic groups. Immunogenetics 52:195–205

    Article  PubMed  CAS  Google Scholar 

  11. Jiang K, Zhu FM, Lv QF, Yan LX (2005) Distribution of killer cell immunoglobulin-like receptor genes in the Chinese Han population. Tissue Antigens 65:556–563

    Article  PubMed  CAS  Google Scholar 

  12. Rajalingam R, Krausa P, Shilling HG, Stein JB, Balamurugan A, McGinnis MD, Cheng NW, Mehra NK, Parham P (2002) Distinctive KIR and HLA diversity in a panel of north Indian Hindus. Immunogenetics 53:1009–1019

    Article  PubMed  CAS  Google Scholar 

  13. Maxwell LD, Ross OA, Curran MD, Rea IM, Middleton D (2004) Investigation of KIR diversity in immunosenescence and longevity within the Irish population. Exp Gerontol 39:1223–1232

    Article  PubMed  CAS  Google Scholar 

  14. Whang DH, Park H, Yoon JA, Park MH (2005) Haplotype analysis of killer cell immunoglobulin-like receptor genes in 77 Korean families. Hum Immunol 66:146–154

    Article  PubMed  CAS  Google Scholar 

  15. Niokou D, Spyropoulou-Vlachou M, Darlamitsou A, Stavropoulos-Giokas C (2003) Distribution of killer cell immunoglobulin-like receptors in the Greek population. Hum Immunol 64:1167–1176

    Article  PubMed  CAS  Google Scholar 

  16. Witt CS, Dewing C, Sayer DC, Uhrberg M, Parham P, Christiansen FT (1999) Population frequencies and putative haplotypes of the killer cell immunoglobulin-like receptor sequences and evidence for recombination. Transplantation 68:1784–1789

    Article  PubMed  CAS  Google Scholar 

  17. Gutierrez-Rodriguez ME, Sandoval-Ramirez L, Diaz-Flores M, Marsh SG, Valladares-Salgado A, Madrigal JA, Mejia-Arangure JM, Garcia CA, Huerta-Zepeda A, Ibarra-Cortes B, Ortega-Camarillo C, Cruz M (2006) KIR gene in ethnic and Mestizo populations from Mexico. Hum Immunol 67:85–93

    Article  PubMed  CAS  Google Scholar 

  18. 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 3:86–95

    Article  PubMed  CAS  Google Scholar 

  19. Majorczyk E, Luszczek W, Nowak I, Pawlik A, Wisniewski A, Jasek M, Kusnierczyk P (2008) Distribution of killer cell immunoglobulin-like receptor genes in Poles. Int J Immunogenet 35:405–407

    Article  PubMed  CAS  Google Scholar 

  20. Rudnick CC, Franceschi DS, Marangon AV, Guelsin GA, Sell AM, Visentainer JE (2008) Killer cell immunoglobulin-like receptor gene diversity in a southern Brazilian population from the state of Parana. Hum Immunol 69:872–876

    Article  PubMed  CAS  Google Scholar 

  21. Mahfouz R, Rayes R, Mahfoud Z, Bazarbachi A, Zaatari G (2006) Distribution of killer cell immunoglobulin-like receptors genotypes in the Lebanese population. Tissue Antigens 68:66–71

    Article  PubMed  CAS  Google Scholar 

  22. Cook MA, Moss PA, Briggs DC (2003) The distribution of 13 killer-cell immunoglobulin-like receptor loci in UK blood donors from three ethnic groups. Eur J Immunogenet 30:213–221

    Article  PubMed  CAS  Google Scholar 

  23. Toneva M, Lepage V, Lafay G, Dulphy N, Busson M, Lester S, Vu-Trien A, Michaylova A, Naumova E, McCluskey J, Charron D (2001) Genomic diversity of natural killer cell receptor genes in three populations. Tissue Antigens 57:358–362

    Article  PubMed  CAS  Google Scholar 

  24. Rayes R, Bazarbachi A, Khazen G, Sabbagh A, Zaatari G, Mahfouz R (2008) Natural killer cell immunoglobulin-like receptors (KIR) genotypes in two Arab populations: will KIR become a genetic landmark between nations? Mol Biol Rep 35:225–229

    Article  PubMed  CAS  Google Scholar 

  25. Bontadini A, Testi M, Cuccia MC, Martinetti M, Carcassi C, Chiesa A, Cosentini E, Dametto E, Frison S, Iannone AM, Lombardo C, Malagoli A, Mariani M, Mariotti L, Mascaretti L, Mele L, Miotti V, Nesci S, Ozzella G, Piancatelli D, Romeo G, Tagliaferri C, Vatta S, Andreani M, Conte R (2006) Distribution of killer cell immunoglobulin-like receptors genes in the Italian Caucasian population. J Transl Med 4:44

    Article  PubMed  CAS  Google Scholar 

  26. Denis L, Sivula J, Gourraud PA, Kerdudou N, Chout R, Ricard C, Moisan JP, Gagne K, Partanen J, Bignon JD (2005) Genetic diversity of KIR natural killer cell markers in populations from France, Guadeloupe, Finland, Senegal and Reunion. Tissue Antigens 66:267–276

    Article  PubMed  CAS  Google Scholar 

  27. Flores AC, Marcos CY, Paladino N, Capucchio M, Theiler G, Arruvito L, Pardo R, Habegger A, Williams F, Middleton D, Fainboim L (2007) KIR genes polymorphism in Argentinean Caucasoid and Amerindian populations. Tissue Antigens 69:568–576

    Article  PubMed  CAS  Google Scholar 

  28. Pavlova Y, Kolesar L, Striz I, Jabor A, Slavcev A (2008) Distribution of KIR genes in the Czech population. Int J Immunogenet 35:57–61

    Article  PubMed  CAS  Google Scholar 

  29. Ewerton PD, Leite Mde M, Magalhaes M, Sena L, Melo dos Santos EJ (2007) Amazonian Amerindians exhibit high variability of KIR profiles. Immunogenetics 59:625–630

    Article  PubMed  CAS  Google Scholar 

  30. Becker S, Tonn T, Fussel T, Uhrberg M, Bogdanow M, Seifried E, Seidl C (2003) Assessment of killer cell immunoglobulin like receptor expression and corresponding HLA class I phenotypes demonstrates heterogenous KIR expression independent of anticipated HLA class I ligands. Hum Immunol 64:183–193

    Article  PubMed  CAS  Google Scholar 

  31. Parham P (2005) MHC class I molecules and KIRs in human history, health and survival. Nat Rev Immunol 5:201–214

    Article  PubMed  CAS  Google Scholar 

  32. March S (2000) The organization of HLA genes within the HLA complex. In: Marsh SGE, Parham P, Barber LD (eds) The HLA facts book. Academic Press, London

    Google Scholar 

  33. Carrington M, Norman P (2006) The KIR gene cluster 2003. http://www.ncbi.nlm.nih.gov/books/bookres.fcgi/mono_003/ch1d1.pdf. Accessed 23 Mar 2006

  34. Rajagopalan S, Long EO (2005) Understanding how combinations of HLA and KIR genes influence disease. J Exp Med 201:1025–1029

    Article  PubMed  CAS  Google Scholar 

  35. Kusnierczyk P (2004) Role of killer cell immunoglobulin-like receptors (KIR) in human diseases. Postepy Hig Med Dosw (Online) 58:259–263

    Google Scholar 

  36. Ruggeri L, Capanni M, Mancusi A, Martelli MF, Velardi A (2005) The impact of donor natural killer cell alloreactivity on allogeneic hematopoietic transplantation. Transpl Immunol 14:203–206

    Article  PubMed  CAS  Google Scholar 

  37. Weisstein, Eric W. “Bonferroni Correction.” From MathWorld—a Wolfram web resource. http://mathoworld.wolfram.com./BonferroniCorrection.html

  38. Maxwell LD, Wallace A, Middleton D, Curran MD (2002) A common KIR2DS4 deletion variant in the human that predicts a soluble KIR molecule analogous to the KIR1D molecule observed in the rhesus monkey. Tissue Antigens 60:254–258

    Article  PubMed  CAS  Google Scholar 

  39. Abu-Amero KK, Gonzalez AM, Larruga JM, Bosley TM, Cabrera VM (2007) Eurasian and African mitochondrial DNA influences in the Saudi Arabian population. BMC Evol Biol 7:32

    Article  PubMed  Google Scholar 

  40. Abu-Amero KK, Hellani A, Gonzalez AM, Larruga JM, Cabrera VM, Underhill PA (2009) Saudi Arabian Y-chromosome diversity and its relationship with nearby regions. BMC Genet 10:59

    Article  PubMed  Google Scholar 

  41. Hiby SE, Walker JJ, O’Shaughnessy KM, Redman CW, Carrington M, Trowsdale J, Moffett A (2004) Combinations of maternal KIR and fetal HLA-C genes influence the risk of preeclampsia and reproductive success. J Exp Med 200:957–965

    Article  PubMed  CAS  Google Scholar 

  42. Reich DE, Cargill M, Bolk S, Ireland J, Sabeti PC, Richter DJ, Lavery T, Kouyoumjian R, Farhadian SF, Ward R, Lander ES (2001) Linkage disequilibrium in the human genome. Nature 411:199–204

    Article  PubMed  CAS  Google Scholar 

  43. Long EO (1999) Regulation of immune responses through inhibitory receptors. Annu Rev Immunol 17:875–904

    Article  PubMed  CAS  Google Scholar 

  44. Moretta A, Bottino C, Millo R, Biassoni R (1999) HLA-specific and non-HLA-specific human NK receptors. Curr Top Microbiol Immunol 244:69–84

    PubMed  CAS  Google Scholar 

  45. Parham P (2005) Immunogenetics of killer cell immunoglobulin-like receptors. Mol Immunol 42:459–462

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study was approved and funded by the King Abdul-Aziz City for Science and Technology, Riyadh, Saudi Arabia, as part of a grant number AR-21-04 and by RAC, King Faisal Specialist Hospital and Research Centre. We are grateful to Dr. Ayodele A. Alaiya and Dr. Abdelilah Aboussekhra for critically reviewing the manuscript. We thank Dr. John Amartey for English rectification. We also thank Ms. Samia Al Hashim for help with statistical calculations and the volunteers who were part of this study.

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Correspondence to Khalid Al Hussein.

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Ameera Gaafar, Atia Sheereen are the authors share an equal contribution to the article.

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Gaafar, A., Sheereen, A., Iqneibi, A. et al. Killer cell immunoglobulin-like receptor gene diversity in the Saudi population. Mol Biol Rep 38, 2603–2610 (2011). https://doi.org/10.1007/s11033-010-0401-y

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  • DOI: https://doi.org/10.1007/s11033-010-0401-y

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