Association between HLA-DQB1 alleles and HAM/TSP patients in Khorasan Province

Document Type : Original Article


1 Immunology Research Group, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran

2 Neurology Department and HTLVI Foundation, Ghaem Medical Center, Mashhad University of Medical Sciences, Mashhad, Iran

3 Allergy Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

4 Genetics Department School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran


Objective(s): HTLVI-1 is the first human retrovirus with limited endemic regions in the world. The epidemiological studies have shown that the genetic background and immune response to the virus have a significant role in HTLV-I-associated diseases.  Among the genes are involved in HTLV-I infection, the role of human leukocytes antigen (HLA) have been studied in different population. In the present study we examined the association between HLA-DQB1 alleles and HTLV-I infection in HAM/TSP patients, HTLV-I carriers and healthy controls in north east of Iran, Mashhad.
Materials and Methods:The blood samples of 16 patients with HAM/TSP, 20 HTLV-1 carriers, and 30 healthy individuals were taken and DNA was extracted by salting out method.  HLA-DQB1 typing was performed using PCR-SSP method and the frequency of HLA-DQB1 alleles were compared by Fischer Exact Test.
Results:There was a significant difference between HAM/TSP patients and healthy controls in the frequency of HLA-DQB1*07 (P=0.004, RR=7). Furthermore, we found that possession of HLA- DQB1*02 or HLA-DQB1*05 increased the risk of disease 1.5 times.
Conclusion: The data presented here suggest that both HLA-DQB1*07 and HLA-DQB1*06 are associated with disease development.


1.Farid Hsseini R, Safaei B. The evaluation of virology seroepidemiology HTLV-1 in Khorasan   province. Med J Mashhad Med Sci Univ 1371; 39:86- 89.
2.Fauci AS, Longo D.  The human retroviruses. In: Principles of internal medicine. Editor: Harrison AF. New York: McGraw-Hill companies; 1998.p.1108-1110.
3.Osame M, Usuku J, Izumo S, Ijichi N, Amitani H, Igata A. HTLV-1 associated myelopathy; a new clinical entity. Lancet 1986; 1:1031-1032.
4.Kuefler PR, Bunn PA. Adult T-cell leukaemia/lymphoma. Clin Haematol 1986; 15:695-726.
5.Levine PH, Jafee ES, Manns A, Murphy EL, Clark J, Blattner WA. Human T-cell lymphotropic virus type I and adult T-cell leukemia/lymphoma outside of Japan and the Carbbean Basin. Yale J Boil Med 1988; 61:215-222.
6.Blattner WA, Kalyanaraman VS, Rober-Guroff M, Sliki A. The human type-C retrovirus, HTLV-1, in blacks from the Caribbean region. And relationship to adult T-cell leukemia/lymphoma. Int J Cancers 1982; 30:257-264.
7. Baltnner WA, Blayney DW, Robert-Guroff M, Nakao Y. Epidemiology of Human T-cell leukemia/lymphoma virus. J Infect Dis 1983; 147:406-416.
8. Levine PH, Jafee ES. Manns A, Murphy EL, Clark J, and Blattner, WA. Human T-cell lymphotropic virus type I and adult T-cell leukemia/lymphoma outside of Japan and the Carbbean Basin. Yale J Boil Med 1988; 61: 215-22.
9. Nagai M, Usuku K, Matsumoto W, et al.  Analysis of HTLV-1 proviral load in 202 HAM/TSP patients & 243 asymptomatic HTLV-I carriers: high proviral load strongly predisposes to HAM/TSP.  J Neurovirol 1998; 4: 586-593.
10. Osame M, Usaku K, Isumo S, Ijichi N, Amitani H, Igata A. HTLV-I-associated mylopathy: a new clinicalentity. Lancet 1986; 1:1031-1032.
11. Christine V. F. Carrington, Elli Kondeatis,D. Dan Ramdath, Paul J. Norman, Robert W. Vaughan, and Henry A. F. Stephens: A Comparison of HLA-DR and -DQ Allele and Haplotype Frequencies in Trinidadian Populations of African, South Asian, and Mixed Ancestry. Human Immunology 2002; 63:1045–1054.
12. Niewiesk S, Bangham CRM. Evolution in a chronic RNA virus infection: selection on HTLV-1 Tax protein differs between healthy carriers and patients with tropical spastic paraparesis. Mol Evol 1996; 42:452-458.
13. Muller N. The epidemiology of HTLV-1 infection. Cancer Cases Control 1991; 2:37-52.
14. Jeffery KJ, Siddiqui AA, Bunce M, Lloyd AL, Vine AM, Witkover AD, et al. The influence of HLA class I alleles and heterozygosity on the outcome of human T cell lymphotropic virus type I infection. J Immunol 2000; 165:7278-7284.
15. Jeffery KJ, Usuka K, Hall SE, Matsumoto W, Taylor GP, Procter J, et al. HLA alleles determine human T-lymphotropic virus-1 (HTLV-1) proviral load  and the risk of HTLV-I- Associated myelopathy. Proc Natl Acad Sci USA 1999; 96:3848-3853.
16. Rezaieyazdi1 Z, Tavakkol-Afshari J, Esmaili E, Orouji E, Pezeshkpour F, Khodadoost M, et al. Association of HLA-DQB1 allelic sequence variation with susceptibility to systemic lupus erythematosus. Iran J Allergy Asthma Immunol 2008; 7:91-95.
17. Itoh Y, Mizuki N, Shimada T, Azuma F, Itakura M, Kashiwase K, et al. High-throughput DNA typing of HLA-A, -B, -C, and -DRB1 loci by a PCR–SSOP–Luminex method in the Japanese population. Immunogenetics 2005; 57:717–729.