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Mol Genet Genomic Med. 2013 Sep;1(3):123-30. doi: 10.1002/mgg3.14. Epub 2013 Jun 7.

The +3187A/G HLA-G polymorphic site is associated with polar forms and reactive reaction in leprosy.

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  • 1Departamento de Imunologia, Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz 50670-420, Recife-PE, Brazil ; Laboratório de Biologia Molecular, Departamento de Oncologia Pediátrica, Hospital IMIP 50070-550, Recife-PE, Brazil ; Divisão de Imunologia Clínica, Departamento de Medicina, Escola de Medicina de Ribeirão Preto, Universidade de São Paulo 14040-900, Ribeirão Preto-SP, Brazil.
  • 2Departamento de Dermatologia da Universidade de Pernambuco e Centro Integrado de Saúde Amaury de Medeiros, Secretaria de Saúde de Pernambuco 52030-010, Recife-PE, Brazil.
  • 3Laboratório de Biologia Molecular, Departamento de Oncologia Pediátrica, Hospital IMIP 50070-550, Recife-PE, Brazil.
  • 4Departamento de Imunologia, Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz 50670-420, Recife-PE, Brazil ; Divisão de Imunologia Clínica, Departamento de Medicina, Escola de Medicina de Ribeirão Preto, Universidade de São Paulo 14040-900, Ribeirão Preto-SP, Brazil.
  • 5Laboratorio de Métodos Quantitativos, Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz 50670-420, Recife-PE, Brazil.
  • 6Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo 14040-901, Ribeirão Preto-SP, Brazil.
  • 7Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Goias - UFG 74001-970, Goiânia-GO, Brazil.
  • 8Divisão de Imunologia Clínica, Departamento de Medicina, Escola de Medicina de Ribeirão Preto, Universidade de São Paulo 14040-900, Ribeirão Preto-SP, Brazil.

Abstract

Considering that variability in immune response genes has been associated with susceptibility to leprosy and with disease severity, leprosy presents clinicopathological variants that are highly associated with the immune response, HLA-G has a well-recognized role in the modulation of the immune response, and polymorphisms at the 3' untranslated region (UTR) of the HLA-G gene may influence HLA-G production, we studied the polymorphic sites at the 3' UTR of the HLA-G gene in leprosy and their association with disease severity. We evaluated by sequencing analysis the allele, genotype, and haplotype frequencies of the 3' UTR HLA-G polymorphic sites (14-bpINDEL/+3003C-T/+3010C-G/+3027A-C/+3035C-T/+3142C-G/+3187A-G/+3196C-G) in 146 individuals presenting reactive leprosy from a highly endemic area, and associated with bacillary load and the type of reactive leprosy. A total of 128 healthy subjects were also studied. Allele, genotype, and haplotype frequencies for the 3' UTR HLA-G polymorphisms in leprosy patients did not differ from those observed in healthy donors. The +3187A allele was responsible for protection against the development of multibacillary leprosy in a dominant model (AA + AG)/GG, OR = 0.11, P = 0.018), and the +3187A allele and +3187A-A genotype were overrepresented in type II reactive leprosy reaction. The effect of genetic factors on leprosy susceptibility may be hidden by environmental components in highly endemic areas. The HLA-G + 3187A polymorphic site, which is related to unstable mRNA production, was associated with the development of polar forms of leprosy and reactive leprosy reaction.

KEYWORDS:

3′ UTR polymorphism; HLA-G; Hansenic reaction; leprosy

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