Original Article

Human Leukocyte Antigen (HLA) Class I and II Polymorphism in Iranian Healthy Population from Yazd Province


The major histocompatibility complex (MHC) genes are the most polymorphic loci in the human genome and have been widely studied in various populations and ethnic groups. Investigations into the HLA genes and proteins have been useful tool for anthropological, transplantation and disease association studies. The polymorphism of the HLA class I (A, B, C) and class II (DRB1, DQA1, DQB1) genes were investigated in 90 unrelated Iranian individuals from Yazd province located in the center of Iran using sequence-specific primers (PCR-SSP). Allele and haplotype frequencies, expected/observed heterozygosity, unbiased expected heterozygosity, number of effective alleles, deviations from Hardy-Weinberg (HW) equilibrium and genetic diversity were computed. A total of 23, 48, 23, 24, 13 and 16 alleles for HLA-A, -B,-C, -DRB1, -DQA and -DQB loci were determined, respectively in the population study. The most frequent allele identified in this study were A*02:01 (18.889%), HLA-B* 51:01 (12.778%), HLA-C* 12:03 (17.033%), HLA-DRB* 11 (24.4%), HLA-DQA* 05:05 (20.55%) and HLA-DQB*03:01 (22.8%).Furthermore, the most frequent 3-locus haplotypes were DRB*11-DQA*05:01-DQB*03:01 (21.1%), HLA-A*02:01- B *50:01- DRB*07:01 (4.9%) and A*26:01 –B* 38:01 –C*12:03(5%). The most 4-locus haplotype were A*11:01 –B* 52:01 –C*12:03 –DRB!*15(2.5%) and A*02:01 –B* 50:01 –DRB1*07:01 –DQB1*02:01(4.5%). The heterozygosity of the study population was confirmed the expected value and not deviated from Hardy-Weinberg equilibrium for all loci (p>0.05). Our study shows a close relatedness between Yazd population and other ethnic group of Iran despite some differences, which may be due to admixture of each one of these groups with each other or foreigner subpopulations during centuries. Moreover, the results of this study suggest that the Iranian population from Yazd province is in close vicinity with the Caucasians populations and far from the Korean and Japanese populations. 

1.Schipper R, D'Amaro J, Bakker J, Bakker J, Van Rood J, Oudshoorn M. HLA gene and haplotype frequencies in bone marrow donors worldwide registries. Human immunology. 1997;52(1):54-71.

2. Amirzargar A, Tabasi A, Khosravi F, Kheradvar A, Rezaei N, Naroueynejad M, et al. Optic neuritis, multiple sclerosis and human leukocyte antigen: results of a 4‐year follow‐up study. European journal of neurology. 2005;12(1):25-30.

3. Amirzargar A, Yalda A, Hajabolbaghi M, Khosravi F, Jabbari H, Rezaei N, et al. The association of HLA-DRB, DQA1, DQB1 alleles and haplotype frequency in Iranian patients with pulmonary tuberculosis. The International Journal of Tuberculosis and Lung Disease. 2004;8(8):1017-21.

4. Gibert M, Balandraud N, Touinssi M, Mercier P, Roudier J, Reviron D. Functional categorization of HLA-DRB1 alleles in rheumatoid arthritis: the protective effect. Human immunology. 2003;64(10):930-5.

5. Khosravi F, Amirzargar A, Sarafnejad A, Nicknam MH, Alimoghadam K, Dianat S, et al. HLA class II allele and haplotype frequencies in Iranian patients with leukemia. Iranian Journal of Allergy, Asthma and Immunology. 2007;6(3):137-42.

6. Larsen CE, Alper CA. The genetics of HLA-associated disease. Current opinion in immunology. 2004;16(5):660-7.

7. Arnaiz‐Villena A, Gomez‐Casado E, Martinez‐Laso J. Population genetic relationships between Mediterranean populations determined by HLA allele distribution and a historic perspective. Tissue antigens. 2002;60(2):111-21.

8. Arnaiz‐Villena A, Iliakis P, González‐Hevilla M, Longás J, Gómez‐Casado E, Sfyridaki K, et al. The origin of Cretan populations as determined by characterization of HLA alleles. Tissue Antigens. 1999;53(3):213-26.

9. Grubic Z, Stingl K, Martinez N, Palfi B, Brkljacic-Kerhin V, Kastelan A, editors. STR and HLA analysis in paternity testing. International Congress Series; 2004: Elsevier.

10. Riley E, Olerup O. HLA polymorphisms and evolution. Immunology today. 1992;13(9):333-5.

11. Longmate J, York J, La Rosa C, Krishnan R, Zhang M, Senitzer D, et al. Population coverage by HLA class-I restricted cytotoxic T-lymphocyte epitopes. Immunogenetics. 2001;52(3-4):165-73.

12. Cavalli-Sforza LL, Piazza A, Menozzi P, Mountain J. Reconstruction of human evolution: bringing together genetic, archaeological, and linguistic data. Proceedings of the National Academy of Sciences. 1988;85(16):6002-6.

13. Nei M, Roychoudhury AK. Evolutionary relationships of human populations on a global scale. Molecular biology and evolution. 1993;10(5):927-43.

14. Amirzargar A, Mytilineos J, Farjadian S, Doroudchi M, Scherer S, Opelz G, et al. Human leukocyte antigen class II allele frequencies and haplotype association in Iranian normal population. Human Immunology. 2001;62(11):1234-8.

15. Farjadian S, Ghaderi A. Iranian Lurs genetic diversity: an anthropological view based on HLA class II profiles. Iran J Immunol. 2006;3:106-13.

16. Farjadian S, Ghaderi A. HLA class II genetic diversity in Arabs and Jews of Iran. Iran J Immunol. 2007;4(2):85-93.

17. Khazaei H, Aghamohammadi A, Rezaei N, Nikbin B, Khosravi M, MiriMoghaddam I, editors. Major histocompatibility complex class I and II antigens frequencies in Baloch ethnic group living in the southeast region of Iran. Transplantation proceedings; 2004: Elsevier.

18. Khazaei HA, Rezaei N, Aghamohammadi A, Amirzargar AA, Ghasemi KM, MiriMoghaddam I, et al. Human leukocyte antigen profile of two ethnic groups in southeast of Iran. Iranian Journal of Allergy, Asthma and Immunology. 2007;6(4):223-4.

19. Farjadian S, Moqadam F, Ghaderi A. HLA class II gene polymorphism in Parsees and Zoroastrians of Iran. International journal of immunogenetics. 2006;33(3):185-91.

20. Farjadian S, Ghaderi A. HLA class II similarities in Iranian Kurds and Azeris. International journal of immunogenetics. 2007;34(6):457-63.

21. Olerup O, Aldener A, Fogdell A. HLA‐DQB1 and‐DQA1 typing by PCR amplification with sequence‐specific primers (PCR‐SSP) in 2 hours. Tissue antigens. 1993;41(3):119-34.

22. Excoffier L, Laval G, Schneider S. Arlequin (version 3.0): an integrated software package for population genetics data analysis. Evolutionary bioinformatics online. 2005;1:47.

23. Nei M. Analysis of gene diversity in subdivided populations. Proceedings of the National Academy of Sciences. 1973;70(12):3321-3.

24. Takezaki N, Nei M, Tamura K. POPTREE2: Software for constructing population trees from allele frequency data and computing other population statistics with Windows interface. Molecular biology and evolution. 2010;27(4):747-52.

25. Saitou N, Nei M. The neighbor-joining method: a new method for reconstructing phylogenetic trees. Molecular biology and evolution. 1987;4(4):406-25.

26. Ihaka R, Gentleman R. R: A Language for Data Analysis and Graphics. Journal of computational and graphical statistics. 1996;5(3):299-314.

27. Arnaiz-Villena A, Benmamar D, Alvarez M, Diaz-Campos N, Varela P, Gomez-Casado E, et al. HLA allele and haplotype frequencies in Algerians: Relatedness to Spaniards and Basques. Human immunology. 1995;43(4):259-68.

28. Bias W. Proceedings of the 12th International Histocompatibility Workshop. 1997;1:353.

29. Martinez‐Laso J, Gazit E, Gomez‐Casado E, Morales P, Martinez‐Quiles N, Alvarez M, et al. HLA DR and DQ polymorphism in Ashkenazi and non‐Ashkenazi Jews: comparison with other Mediterraneans. Tissue antigens. 1996;47(1):63-71.

30. Arnaiz‐Villena A, Dimitroski K, Pacho A, Moscoso J, Gómez‐Casado E, Silvera‐Redondo C, et al. HLA genes in Macedonians and the sub‐Saharan origin of the Greeks. Tissue Antigens. 2001;57(2):118-27.

31. Farjadian S, Naruse T, Kawata H, Ghaderi A, Bahram S, Inoko H. Molecular analysis of HLA allele frequencies and haplotypes in Baloch of Iran compared with related populations of Pakistan. Tissue antigens. 2004;64(5):581-7.

32. Uinuk-ool TS, Takezaki N, Sukernik RI, Nagl S, Klein J. Origin and affinities of indigenous Siberian populations as revealed by HLA class II gene frequencies. Human genetics. 2002;110(3):209-26.

33. Donadi E. Proceedings of the 13th International Histocompatibility Workshop. 2006.

34. Gómez‐Casado E, Del Moral P, Martínez‐Laso J, García‐Gómez A, Allende L, Silvera‐Redondo C, et al. HLA genes in Arabic‐speaking Moroccans: close relatedness to Berbers and Iberians. Tissue Antigens. 2000;55(3):239-49.

35. Gonzalez-Galarza FF, Christmas S, Middleton D, Jones AR. Allele frequency net: a database and online repository for immune gene frequencies in worldwide populations. Nucleic acids research. 2011;39(suppl 1):D913-D9.

36. Roitberg‐Tambur A, Witt C, Friedmann A, Safirman C, Sherman L, Battat S, et al. Comparative analysis of HLA polymorphism at the serologic and molecular level in Moroccan and Ashkenazi Jews. Tissue Antigens. 1995;46(2):104-10.

37. Ferencik S, Gong F, Grosse-Wilde H. HLA-A,-B,-Cw,-DQB1 and-DRB1 alleles in a population from Wuhan, China. Human Immunology. 2004;65(9):905-6.

38. Arnaiz-Villena A, Martinez-Laso J, Moscoso J, Livshits G, Zamora J, Gomez-Casado E, et al. HLA genes in the Chuvashian population from European Russia: admixture of Central European and Mediterranean populations. Human biology. 2003:375-92.

39. Arnaiz-Villena A, Elaiwa N, Silvera C, Rostom A, Moscoso J, Gómez-Casado E, et al. The origin of Palestinians and their genetic relatedness with other Mediterranean populations. Human Immunology. 2001;62(9):889-900.

40. Grahovac B, Sukernik RI, O’hUigin C, Zaleska-Rutczynska Z, Blagitko N, Raldugina O, et al. Polymorphism of the HLA class II loci in Siberian populations. Human genetics. 1998;102(1):27-43.

41. Kapustin S, Lyshchov A, Alexandrova J, Imyanitov E, Blinov M. HLA class II molecular polymorphisms in healthy Slavic individuals from North‐Western Russia. Tissue Antigens. 1999;54(5):517-20.

42. Reil A, Bein G, Machulla H, Sternberg B, Seyfarth M. High‐resolution DNA typing in immunoglobulin A deficiency confirms a positive association with DRB 1* 0301, DQBl* 02 haplotypes. Tissue Antigens. 1997;50(5):501-6.

43. Yabuki K, Ohno S, Mizuki N, Ando H, Tabbara K, Goto K, et al. HLA class I and II typing of the patients with Behçet’s disease in Saudi Arabia. Tissue Antigens. 1999;54(3):273-7.

44. Rey D, Amirzargar A, Areces C, Enríquez-de-Salamanca M, Marco J, Abd-El-Fatah-Khalil S, et al. Gorgan (Turkmen in Iran) HLA genetics: transplantation, pharmacogenomics and anthropology. Immunological investigations. 2015;44(1):88-100.

45. Martinez‐Laso J, Juan D, Martinez‐Quiles N, Gomez‐Casado E, Cuadrado E, Arnaiz‐Villena A. The contribution of the HLA‐A,‐B,‐C and‐DR,‐DQ DNA typing to the study of the origins of Spaniards and Basques. Tissue Antigens. 1995;45(4):237-45.

46. Papassavas EC, Spyropoulou-Vlachou M, Papassavas AC, Schipper RF, Doxiadis IN, Stavropoulos-Giokas C. MHC class I and class II phenotype, gene, and haplotype frequencies in Greeks using molecular typing data. Human immunology. 2000;61(6):615-23.

47. Paximadis M, Mathebula TY, Gentle NL, Vardas E, Colvin M, Gray CM, et al. Human leukocyte antigen class I (A, B, C) and II (DRB1) diversity in the black and Caucasian South African population. Human immunology. 2012;73(1):80-92.

48. Lee KW, Oh D-H, 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(5):437-47.

49. Amar A, Kwon O, Motro U, Witt C, Bonne-Tamir B, Gabison R, et al. Molecular analysis of HLA class II polymorphisms among different ethnic groups in Israel. Human immunology. 1999;60(8):723-30.

50. Testi M, Mariani M. Caucasian Italian normal. Am Soc Histocompat Immunogenet Lenexa, KS, USA. 1998:165.

51. Martinez-Laso J, Sartakova M, Allende L, Konenkov V, Moscoso J, Silvera-Redondo C, et al. HLA molecular markers in Tuvinians: a population with both Oriental and Caucasoid characteristics. Annals of human genetics. 2001;65(03):245-61.

52. Geng L, Imanishi T, Tokunaga K, Zhu D, Mizuki N, Xu S, et al. Determination of HLA class II alleles by genotyping in a Manchu population in the northern part of China and its relationship with Han and Japanese populations. Tissue Antigens. 1995;46(2):111-6.

53. Maiers M, Gragert L, Klitz W. High-resolution HLA alleles and haplotypes in the United States population. Human immunology. 2007;68(9):779-88.

54. Amirzargar A, Rey D, Muñiz E, Palacio-Grüber J, Nikbin B, Nicknam H, et al. Kurds HLA Genes: Its Implications in Transplantation and Pharmacogenomics. Open Medicine Journal. 2015;2(1).

IssueVol 16, No 1 (2017) QRcode
SectionOriginal Article(s)
Keywords Human leukocyte antigen (HLA) Polymorphism Class I and II Yazd province

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
Nikbin B, Nicknam MH, Hadinedoushan H, Ansaripour B, Moradi B, Yekaninejad M, Aminikhah M, Ranjbar MM, Amirzargar A. Human Leukocyte Antigen (HLA) Class I and II Polymorphism in Iranian Healthy Population from Yazd Province. Iran J Allergy Asthma Immunol. 2017;16(1):1-13.