Abstract
Rheumatoid arthritis (RA [MIM 180300]) is a complex, polygenic inflammatory autoimmune disease, resulting from interactions between genetic and environmental factors. Some of the RA-associated HLA-DRB1 alleles have shared epitope, but their distribution varies among different racial/ethnic groups. This study was aimed at investigating the distribution of HLA-DRB1 alleles in patients with RA in eastern Black Sea region of Turkey. DNA samples of 320 patients with RA and 360 healthy controls were studied for the determination of HLA-DRB1 allele distribution using PCR–SSP method. The allele frequencies of HLA-DRB1*01, *04, and *09 were higher in patients with RA compared with the controls (P < 0.005, P < 0.0001, and P < 0.01, respectively). On the other hand, in patients with RA, HLA-DRB1*13 allele was lower than the controls (P < 0.001). Of the HLA-DRB1*04 subgroups, *0401 (40.83% vs. 18.75%, P < 0.001) was the most frequent allele in patients with RA, while DRB1*0402 (30.00% vs. 12.50%, P < 0.005) allele in the controls. HLA-DRB1 allele frequencies in the patients with RA and the controls showed Hardy–Weinberg rule compliance. Results of this study indicate that HLA-DRB1*01, *04, and *09 alleles were associated with RA, and HLA-DRB1*13 was protective allele against RA. Among the subgroups of HLA-DRB1*04, *0401 was detected to be RA associated, while *0402 was being protective. These results have some differences compared with previous reports originating from other regions of Turkey.
Similar content being viewed by others
References
Nepom GT (2000) HLA and rheumatoid arthritis. In: Lecher R, Warrens A (eds) HLA in health and disease. Academic, London, pp 181–186
Ruddy S, Haris ED, Sledge CB (2001) Kelly’s textbook of rheumatology, 6th edn. Saunders WB Company, London
Harney S, Wordsworth BP (2002) Genetic epidemiology of rheumatoid arthritis. Tissue Antigens 60:465–473
Dieude P, Cornelis F (2005) Genetic basis of rheumatoid arthritis. Joint Bone Spine 72:520–526
Capkin E, Cakirbay H, Karkucak M et al (2010) Prevalence of rheumatoid arthritis in the eastern Black Sea region of Turkey. Int J Rheum Dis 13:380–384
Orozco G, Rueda B, Martin J (2006) Rheumatoid arthritis: genetic basis of rheumatoid arthritis. Biomed Pharmacother 60:656–662
Barnetche T, Constantin A, Cantagrel A, Cambon-Thomsen A, Gourraud PA (2008) New classification of HLA-DRB1 alleles in rheumatoid arthritis susceptibility: a combined analysis of worldwide samples. Arthritis Res Ther 10:R26
Pratt AG, Isaacs JD, Mattey DL (2009) Current concepts in the pathogenesis of early rheumatoid arthritis. Best Pract Res Clin Rheumatol 23:37–48
Gregersen PK, Silver J, Winchester RJ (1987) The shared epitope hypothesis: an approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum 30:1205–1213
Kochi Y, Suzuki A, Yamada R, Yamamoto K (2009) Genetics of rheumatoid arthritis: underlying evidence of ethnic differences. J Autoimmun 32:158–162
Bowes J, Barton A (2008) Recent advances in the genetics of RA susceptibility. Rheumatology 47:399–402
Newton JL, Harney SMJ, Wordsworth BP, Brown MA (2004) A review of MHC genetics of rheumatoid arthritis. Genes Immunity 5:151–157
Yan Z, Ferucci ED, Geraghty DE, Yang Y, Lanier AP, Smith WP et al (2007) Resequencing of the human major histocompatibility complex in patients with rheumatoid arthritis and healthy controls in Alaska Natives of Southeast Alaska. Tissue Antigens 70:487–494
Weyand CM, Goronzy JJ (2000) Association of MHC and rheumatoid arthritis HLA polymorphism in phenotypic variants of rheumatoid arthritis. Arthritis Res 2:212–216
Imboden JB (2009) The immunopathogenesis of rheumatoid arthritis. Annu Rev Pathol 4:417–434
Gough SCL, Simmonds MJ (2007) The HLA region and autoimmune disease: associations and mechanism of action. Current Genomics 8:453–465
Kilding R, Wilson AG (2005) Mapping of a novel susceptibility gene for rheumatoid arthritis in telomeric MHC region. Cytokine 32:71–75
Alvarez I, Collado J, Daura X, Colomé N, Rodríguez-García M, Gallart T et al (2008) The rheumatoid arthritis-associated allele HLA–DR10 (DRB1*1001) shares part of its repertoire with HLA–DR1 (DRB1*0101) and HLA–DR4 (DRB*0401). Arthritis Rheum 58:1630–1639
Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS et al (1988) The American rheumatism association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324
Excoffier L, Laval G, Schneider S (2005) Arlequin ver. 3.0 An integrated software package for population genetics data analysis. Evol Bioinform Online 1:47–50
Gonzalez-Gay MA, Garcia-Porrua C, Hajeer AH (2002) Influence of human leukocyte antigen-DRB1 on the susceptibility and severity of rheumatoid arthritis. Semin Arthritis Rheum 31:355–360
Reviron D, Foutrier C, Guist S, Mercier P, Roudier J (2001) DRB1 alleles in polymyalgia rheumatica and rheumatoid arthritis in southern France. Eur J Immunogenet 28:83–87
Auger I, Roudier C, Guis S, Balandraud N, Roudier J (2007) HLA-DRB1*0404 is strongly associated with anti-calpastin antibodies in rheumatoid arthritis. Ann Rheum Dis 66:1588–1593
Hajeer AH, Dababneh A, Makki RF, Thomson W, Poulton K, Gonzalez-Gay MA et al (2000) Different gene loci within the HLA-DR and TNF regions are independently associated with susceptibility and severity in Spanish rheumatoid arthritis patients. Tissue Antigens 55:319–325
Saruhan-Direskeneli G, SG IR (1998) Shared epitope “Homozygosity” is strongly associated with RA patients in Turkey. Br J Rheumatol 37:1126–1128
Delgado-Vega AM, Anaya JM (2007) Meta-analysis of HLA-DRB1 polymorphism in Latin American patients with rheumatoid arthritis. Autoimmun Rev 6:402–408
del Rincon I, Escalante A (1999) HLA-DRB1 alleles associated with susceptibility or resistance to rheumatoid arthritis, articular deformities, and disability in Mexican Americans. Arthritis Rheum 42:1329–1338
Al-Swailem R, Al-Rayes H, Sobki S, Arfin M, Tariq M (2006) HLA-DRB1 association in Saudi rheumatoid arthritis patients. Rheumatol Int 26:1019–1024
Takeuchi F, Nakano K, Matsuta K, Nabeta H, Bannai M, Tanimoto K, Ito K (1996) Positive and negative association of HLA-DR genotypes with Japanese rheumatoid arthritis. Clin Exp Rheumatol 14:17–22
Zhao Y, Dong Y, Zhu X, Qiu C (1996) HLA-DRB1 alleles genotyping in patients with rheumatoid arthritis in Chinese. Chin Med Sci J 11:232–235
Jun KR, Choi SE, Cha CH, Oh HB, Heo YS, Ahn HY, Lee KJ (2007) Meta-analysis of the association between HLA-DRB1 allele and rheumatoid arthritis susceptibility in Asian populations. J Korean Med Sci 22:973–980
Kinikli G, Ateş A, Turgay M, Akay G, Kinikli S, Tokgöz G (2003) HLA-DRB1 genes and disease severity in rheumatoid arthritis in Turkey. Scand J Rheumatol 32:277–280
Milicic A, Lee D, Brown MA, Darke C, Wordsworth BP (2002) HLA-DR/DQ haplotype in rheumatoid arthritis: novel allelic associations in UK Caucasians. J Rheumatol 29:1821–1826
Lee HS, Lee KW, Kim SongGG, HA KimSY, Bae SC (2004) Increased susceptibility to rheumatoid arthritis in koreans heterozygous for HLA–DRB1*0405 and *0901. Arthritis Rheum 50:3468–3475
Kim TG, Choi HB, Park SH, Kim HY, Han H (1999) DQCAR 113 and DQCAR 115 in combination with HLA-DRB1 alleles are significant markers of susceptibility to rheumatoid arthritis in the Korean population. Tissue Antigens 54:552–559
Sahin N, Gündüz F, Inanç N (2009) No association of PTPN22 gene polymorphism with rheumatoid arthritis in Turkey. Rheomatol Int 30:81–83
Baki A, Karagüzel A, Beşer E, Cakmakçi T, Uçar F, Omeroglu A (1992) Consanguineous marriages in The Province of Trabzon, Turkey. East Afr Med J 69:94–96
Gonzalez-Gay MA, Nabozny GH, Bull MJ, Zanelli E, Douhan J 3rd, Griffiths MM et al (1994) Protective role of major histocompatibility complex class II Ebd transgene on collagen-induced arthritis. J Exp Med 180:1559–1564
Mattey DL, Dawes PT, Gonzalez-Gay MA, Garcia-Porrua C, Thomson W, Hajeer AH et al (2001) HLA-DRB1 alleles encoding an aspartic acid at position 70 protect against development of rheumatoid arthritis. J Rheumatol 28:232–239
Hughes LB, Morrison D, Kelley JM, Padilla MA, Vaughan LK, Westfall AO et al (2008) The HLA-DRB1 shared epitope is associated with susceptibility to rheumatoid arthritis in African Americans through European genetic admixture. Arthritis Rheum 58:349–358
Xue Y, Zhang J, Chen YM, Guan M, Zheng SG, Zou HJ (2008) The HLA-DRB1 shared epitope is not associated with antibodies against cyclic citrullinated peptide in Chinese patients with rheumatoid arthritis. Scand J Rheumatol 37:183–187
de Vries N, Tijssen H, van Riel PL, van de Putte LB (2002) Reshaping the shared epitope hypothesis: HLA-associated risk for rheumatoid arthritis is encoded by amino acid substitutions at positions 67–74 of the HLA-DRB1 molecule. Arthritis Rheum 46:921–928
Tuokko J, Nejentsev LuukkainenR, Toivanen A, Ilonen J (2001) HLA haplotype analysis in Finnish patients with rheumatoid arthritis. Arthritis Rheum 44:315–322
Morgan AW, Haroon-Rashid L, Martin SG et al (2008) The shared epitope hypothesis in rheumatoid arthritis: evaluation of alternative classification criteria in a large UK Caucasian cohort. Arthritis Rheum 58:1275–1283
Acknowledgments
This work was supported by a grant from Karadeniz Technical University Scientific Research Fund (Grant No: 2007.114.001.6).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Uçar, F., Karkucak, M., Alemdaroğlu, E. et al. HLA-DRB1 allele distribution and its relation to rheumatoid arthritis in eastern Black Sea Turkish population. Rheumatol Int 32, 1003–1007 (2012). https://doi.org/10.1007/s00296-010-1792-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00296-010-1792-8