title: HLA-DR and HLA-DQ alleles in patients from the south of Brazil: markers for leprosy susceptibility and resistance.
abstract: BACKGROUND
  Many epidemiological studies have shown that the genetic factors of the host play a role in the variability of clinical response to infection caused by M. leprae. With the purpose of identifying genes of susceptibility, the present study investigated the possible role of HLA-DRB1 and DQA1/DQB1 alleles in susceptibility to leprosy, and whether they account for the heterogeneity in immune responses observed following infection in a Southern Brazilian population.
  
  
  METHODS
  One hundred and sixty-nine leprosy patients and 217 healthy controls were analyzed by polymerase chain reaction amplification and reverse hybridization with sequence-specific oligonucleotide probes and sequence-specific primers (One Lambda, CA, USA).
  
  
  RESULTS
  There was a positive association of HLA-DRB1*16 (*1601 and *1602) with leprosy per se (7.3% vs. 3.2%, P = 0.01, OR = 2.52, CI = 1.26-5.01), in accord with previous serological studies, which showed DR2 as a marker of leprosy. Although, HLA-DQA1*05 frequency (29.8% vs. 20.9%, P = 0.0424, OR = 1.61, CI = 1.09-2.39) was higher in patients, and HLA-DQA1*02 (3.0% vs. 7.5%, P = 0.0392, OR = 0.39, CI = 0.16 - 0.95) and HLA-DQA1*04 (4.0% vs. 9.1%, P = 0.0314, OR = 0.42, CI = 0.19 - 0.93) frequencies lower, P-values were not significant after the Bonferroni's correction. Furthermore, HLA-DRB1*1601 (9.0% vs. 1.8%; P = 0.0016; OR = 5.81; CI = 2.05-16.46) was associated with susceptibility to borderline leprosy compared to control group, and while HLA-DRB1*08 (11.2% vs. 1.2%; P = 0.0037; OR = 12.00; CI = 1.51 - 95.12) was associated with susceptibility to lepromatous leprosy, when compared to tuberculoid leprosy, DRB1*04 was associated to protection.
  
  
  CONCLUSIONS
  These data confirm the positive association of HLA-DR2 (DRB1*16) with leprosy per se, and the protector effect of DRB1*04 against lepromatous leprosy in Brazilian patients.
authors.affiliation: Departamento de Análises Clínicas, Universidade Estadual de Maringá, Paraná, Brazil. samira_paes@hotmail.com
authors.forename: Samira A
authors.initials: SA
authors.lastname: da Silva
authors.forename: Priscila S
authors.initials: PS
authors.lastname: Mazini
authors.forename: Pâmela G
authors.initials: PG
authors.lastname: Reis
authors.forename: Ana M
authors.initials: AM
authors.lastname: Sell
authors.forename: Luiza T
authors.initials: LT
authors.lastname: Tsuneto
authors.forename: Paulo R
authors.initials: PR
authors.lastname: Peixoto
authors.forename: Jeane E L
authors.initials: JE
authors.lastname: Visentainer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001938:Brazil; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics* / Q000276:immunology; D059848:HLA-DQ alpha-Chains; D006684:HLA-DR Antigens / Q000235:genetics* / Q000276:immunology; D059811:HLA-DRB1 Chains; D006801:Humans; D015440:Leprosy, Lepromatous / Q000235:genetics* / Q000276:immunology; D015441:Leprosy, Tuberculoid / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D055815:Young Adult
chemical_list: D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; C069050:HLA-DQA1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains
references.citation: Bull World Health Organ. 1966;34(6):827-57
references.pmid: 5330347
references.citation: Trends Microbiol. 1998 Apr;6(4):148-54
references.pmid: 9587192
references.citation: Tissue Antigens. 1987 Mar;29(3):146-53
references.pmid: 3603547
references.citation: Annu Rev Immunol. 1993;11:403-50
references.pmid: 8476568
references.citation: Int J Lepr Other Mycobact Dis. 2000 Mar;68(1):49-56
references.pmid: 10834069
references.citation: N Engl J Med. 2000 Sep 14;343(11):782-6
references.pmid: 10984567
references.citation: Tissue Antigens. 2005 May;65(5):437-47
references.pmid: 15853898
references.citation: Braz J Med Biol Res. 1997 Jan;30(1):51-9
references.pmid: 9222403
references.citation: Tuberculosis (Edinb). 2004;84(1-2):82-92
references.pmid: 14670349
references.citation: Enferm Infecc Microbiol Clin. 2007 Dec;25(10):627-31
references.pmid: 18053473
references.citation: Clin Dermatol. 2007 Mar-Apr;25(2):165-72
references.pmid: 17350495
references.citation: Tissue Antigens. 2007 Dec;70(6):455-63
references.pmid: 17900288
references.citation: J Biomed Biotechnol. 2003;2003(3):208-211
references.pmid: 12975536
references.citation: Curr Opin Immunol. 2005 Feb;17(1):44-8
references.pmid: 15653309
references.citation: Tissue Antigens. 1993 Sep;42(3):133-7
references.pmid: 8284786
references.citation: Tissue Antigens. 1992 May;39(5):225-35
references.pmid: 1357775
references.citation: Genes Immun. 2007 Jun;8(4):320-4
references.pmid: 17396103
references.citation: Evol Bioinform Online. 2007 Feb 23;1:47-50
references.pmid: 19325852
references.citation: Vox Sang. 1982;42(5):243-7
references.pmid: 6954762
references.citation: Int J Parasitol. 1999 Sep;29(9):1351-8
references.pmid: 10579423
references.citation: Genes Immun. 2001 Jun;2(4):196-204
references.pmid: 11477474
references.citation: Tissue Antigens. 1985 Oct;26(4):243-7
references.pmid: 3878012
references.citation: Genes Immun. 2004 Jan;5(1):63-7
references.pmid: 14735151
references.citation: Int J Dermatol. 2002 Oct;41(10):681-6
references.pmid: 12390192
references.citation: Clin Exp Dermatol. 2002 May;27(3):235-9
references.pmid: 12072016
references.citation: Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):177-82
references.pmid: 12509516
references.citation: Drug Metab Dispos. 2001 Apr;29(4 Pt 2):479-83
references.pmid: 11259336
references.citation: Microbes Infect. 2006 Apr;8(4):1124-31
references.pmid: 16513393
references.citation: Tissue Antigens. 1992 Sep;40(3):124-7
references.pmid: 1440566
references.citation: Hum Biol. 2000 Aug;72(4):597-617
references.pmid: 11048789