Association of genetic polymorphism of HLA‑DRB1 antigens with the susceptibility to lepromatous leprosy

Escamilla‑Tilch,Monica; Torres‑Carrillo,Nora  Magdalena; Ramos Payan,Rosalio; Aguilar‑Medina,Maribel; Salazar,Ma  Isabel; Fafutis‑Morris,Mary; Arenas‑Guzman,Roberto; Estrada‑Parra,Sergio; Estrada‑Garcia,Iris; Granados,Julio

doi:10.3892/br.2013.167

Association of genetic polymorphism of HLA‑DRB1 antigens with the susceptibility to lepromatous leprosy

Authors:
- Monica Escamilla‑Tilch
- Nora Magdalena Torres‑Carrillo
- Rosalio Ramos Payan
- Maribel Aguilar‑Medina
- Ma Isabel Salazar
- Mary Fafutis‑Morris
- Roberto Arenas‑Guzman
- Sergio Estrada‑Parra
- Iris Estrada‑Garcia
- Julio Granados
View Affiliations

Affiliations: Department of Immunology, National School of Biological Sciences, National Polytechnic Institute, Mexico City 11340, Mexico, Department of Basic Science Research, National Institute of Geriatrics, Ministry of Health, Mexico City, 10200, Mexico, School of Chemical and Biological Sciences, Autonomous University of Sinaloa, Culiacan, Sinaloa 80040, Mexico, Department of Immunology, National School of Biological Sciences, National Polytechnic Institute, Mexico City 11340, Mexico, Center for Research in Immunology and Dermatology, Dermatological Institute of Jalisco, Guadalajara, Jalisco 45190, Mexico, Mycology Section, General Hospital Dr Manuel Gea Gonzalez, Mexico City 14000, Mexico, Department of Transplantation, National Institute of Medical Sciences and Nutrition Salvador Zubiran, Mexico City 14000, Mexico
Published online on: September 19, 2013 https://doi.org/10.3892/br.2013.167
Pages: 945-949

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Despite the introduction of multidrug therapy and the overall reduction of leprosy prevalence in Mexico, the disease remains endemic in certain regions of the country. A genetic basis for the immune susceptibility to Mycobacterium leprae has already been established in different populations worldwide. In this study, we investigated the possible association of the HLA‑DRB1 alleles with leprosy in a Mexican mestizo population. The results demonstrated that the HLA‑DRB1*01 allele is associated with lepromatous and dimorphic leprosy [P<0.001, odds ratio (OR)=4.6, 95% confidence interval (95% CI): 1.8‑11.4; and P=0.03, OR=6.2, 95% CI: 1.1‑31.6, respectively] and the frequency of the HLA‑DRB1*08 allele was found to be significantly lower among leprosy patients compared to controls (P=0.046, OR=2.4, 95% CI: 1‑5.8). In conclusion, although the association of the HLA‑DR locus with leprosy has been established in different populations and several studies have demonstrated significant differences in the DR alleles, this study demonstrated an association of the HLA‑DRB1*01 allele with susceptibility to lepromatous and dimorphic leprosy, as well as an association of the HLA‑DRB1*08 allele with protection against leprosy in a Mexican mestizo population.

View Figures

View References

1	Gulia A, Fried I and Massone C: New insights in the pathogenesis and genetics of leprosy. F1000 Med Rep. 2:302010. View Article : Google Scholar : PubMed/NCBI
2	World Health Organization. Global leprosy situation, 2012. Wkly Epidemiol Rec. 87:317–328. 2012.
3	Lavado-Valenzuela R, José Bravo M, Junqueira-Kipnis AP, et al: Distribution of the HLA class II frequency alleles in patients with leprosy from the mid-west of Brazil. Int J Immunogenet. 38:255–258. 2011. View Article : Google Scholar : PubMed/NCBI
4	Alvarado-Navarro A, Montoya-Buelna M, Munoz-Valle JF, Lopez-Roa RI, Guillen-Vargas C and Fafutis-Morris M: The 3′UTR 1188 A/C polymorphism in the interleukin-12p40 gene (IL-12B) is associated with lepromatous leprosy in the west of Mexico. Immunol Lett. 118:148–151. 2008.
5	Larrea MR, Carreno MC and Fine PE: Patterns and trends of leprosy in Mexico: 1989–2009. Lepr Rev. 83:184–194. 2012.PubMed/NCBI
6	Vanderborght PR, Pacheco AG, Moraes ME, et al: HLA-DRB104 and DRB110 are associated with resistance and susceptibility, respectively, in Brazilian and Vietnamese leprosy patients. Genes Immun. 8:320–324. 2007.
7	Misch EA, Berrington WR, Vary JC Jr and Hawn TR: Leprosy and the human genome. Microbiol Mol Biol Rev. 74:589–620. 2010. View Article : Google Scholar
8	Alter A, Grant A, Abel L, Alcais A and Schurr E: Leprosy as a genetic disease. Mamm Genome. 22:19–31. 2011. View Article : Google Scholar
9	Zhang FR, Huang W, Chen SM, et al: Genomewide association study of leprosy. N Engl J Med. 361:2609–2618. 2009. View Article : Google Scholar : PubMed/NCBI
10	Miller EN, Jamieson SE, Joberty C, et al: Genome-wide scans for leprosy and tuberculosis susceptibility genes in Brazilians. Genes Immun. 5:63–67. 2004. View Article : Google Scholar : PubMed/NCBI
11	Hsieh NK, Chu CC, Lee NS, Lee HL and Lin M: Association of HLA-DRB1*0405 with resistance to multibacillary leprosy in Taiwanese. Hum Immunol. 71:712–716. 2010.
12	Zhang F, Liu H, Chen S, et al: Evidence for an association of HLA-DRB115 and DRB109 with leprosy and the impact of DRB1*09 on disease onset in a Chinese Han population. BMC Med Genet. 10:1332009.
13	Ridley DS and Jopling WH: Classification of leprosy according to immunity. A five-group system. Int J Lepr Other Mycobact Dis. 34:255–273. 1966.PubMed/NCBI
14	Rangel-Villalobos H, Munoz-Valle JF, Gonzalez-Martin A, Gorostiza A, Magana MT and Paez-Riberos LA: Genetic admixture, relatedness, and structure patterns among Mexican populations revealed by the Y-chromosome. Am J Phys Antropol. 135:448–461. 2008. View Article : Google Scholar : PubMed/NCBI
15	Rubi-Castellanos R, Anaya-Palafox M, Mena-Rojas E, Bautista-España D, Munoz-Valle JF and Rangel-Villalobos H: Genetic data of 15 autosomal STRs (Identifiler kit) of three Mexican Mestizo population samples from the States of Jalisco (West), Puebla (Center), and Yucatan (Southeast). Forensic Sci Int Genet. 3:e71–e76. 2009. View Article : Google Scholar : PubMed/NCBI
16	Miller SA, Dykes DD and Polesky HF: A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 16:12151988. View Article : Google Scholar : PubMed/NCBI
17	Yamamoto-Furusho JK, Uscanga LF, Vargas-Alarcon G, Rodriguez-Perez JM, Zuniga J and Granados J: Polymorphisms in the promoter region of tumor necrosis factor alpha (TNF-alpha) and the HLA-DRB1 locus in Mexican mestizo patients with ulcerative colitis. Immunol Lett. 95:31–35. 2004. View Article : Google Scholar : PubMed/NCBI
18	Geluk A and Ottenhoff TH: HLA and leprosy in the pre and postgenomic eras. Hum Immunol. 67:439–445. 2006. View Article : Google Scholar : PubMed/NCBI
19	Blackwell JM and Searle S: Genetic regulation of macrophage activation: understanding the function of Nramp1 (=Ity/Lsh/Bcg). Immunol Lett. 65:73–80. 1999.PubMed/NCBI
20	Gorodezky C, Flores J, Arevalo N, Castro LE, Silva A and Rodriguez O: Tuberculoid leprosy in Mexicans is associated with HLA-DR3. Lepr Rev. 58:401–406. 1987.PubMed/NCBI
21	Gorodezky C, Alaez C, Munguia A, et al: Molecular mechanisms of MHC linked susceptibility in leprosy: towards the development of synthetic vaccines. Tuberculosis (Edinb). 84:82–92. 2004. View Article : Google Scholar : PubMed/NCBI
22	Vargas-Alarcón G, Granados J, Rodriguez-Pérez JM, et al: Distribution of HLA class II alleles and haplotypes in Mexican Mestizo population: comparison with other populations. Immunol Invest. 39:268–283. 2010.PubMed/NCBI
23	da Silva SA, Mazini PS, Reis PG, Sell AM, Tsuneto LT, Peixoto PR and Visentainer JE: HLA-DR and HLA-DQ alleles in patients from the south of Brazil: markers for leprosy susceptibility and resistance. BMC Infect Dis. 9:1342009.PubMed/NCBI
24	Motta PM, Cech N, Fontan C, et al: Role of HLA-DR and HLA-DQ alleles in multibacillary leprosy and paucibacillary leprosy in the province of Chaco (Argentina). Enferm Infecc Microbiol Clin. 25:627–631. 2007.(In Spanish).
25	Zerva L, Cizman B, Mehra NK, et al: Arginine at positions 13 or 70–71 in pocket 4 of HLA-DRB1 alleles is associated with susceptibility to tuberculoid leprosy. J Exp Med. 183:829–836. 1996.
26	Soebono H, Giphart MJ, Schreuder GM, Klatser PR and de Vries RR: Associations between HLA-DRB1 alleles and leprosy in an Indonesian population. Int J Lepr Other Mycobact Dis. 65:190–196. 1997.PubMed/NCBI
27	Hegazy AA, Abdel-Hamid IA, Ahmed el-SF, Hammad SM and Hawas SA: Leprosy in a high-prevalence Egyptian village: epidemiology and risk factors. Int J Dermatol. 41:681–686. 2002. View Article : Google Scholar : PubMed/NCBI
28	Rani R, Fernandez-Vina MA, Zaheer SA, Beena KR and Stastny P: Study of HLA class II alleles by PCR oligotyping in leprosy patients from north India. Tissue Antigens. 42:133–137. 1993. View Article : Google Scholar : PubMed/NCBI
29	Barquera R, Zuñiga J, Hernandez-Diaz R, et al: HLA class I and class II haplotypes in admixed families from several regions of Mexico. Mol Immunol. 45:1171–1178. 2008. View Article : Google Scholar : PubMed/NCBI