MHC Class I Chain-Related Gene A Polymorphisms and Linkage Disequilibrium with HLA-B and HLA-C Alleles in Ocular Toxoplasmosis

PLoS One. 2015 Dec 16;10(12):e0144534. doi: 10.1371/journal.pone.0144534. eCollection 2015.

Abstract

This study investigated whether polymorphisms of the MICA (major histocompatibility complex class I chain-related gene A) gene are associated with eye lesions due to Toxoplasma gondii infection in a group of immunocompetent patients from southeastern Brazil. The study enrolled 297 patients with serological diagnosis of toxoplasmosis. Participants were classified into two distinct groups after conducting fundoscopic exams according to the presence (n = 148) or absence (n = 149) of ocular scars/lesions due to toxoplasmosis. The group of patients with scars/lesions was further subdivided into two groups according to the type of the ocular manifestation observed: primary (n = 120) or recurrent (n = 28). Genotyping of the MICA and HLA alleles was performed by the polymerase chain reaction-sequence specific oligonucleotide technique (PCR-SSO; One Lambda®) and the MICA-129 polymorphism (rs1051792) was identified by nested polymerase chain reaction (PCR-RFLP). Significant associations involving MICA polymorphisms were not found. Although the MICA*002~HLA-B*35 haplotype was associated with increased risk of developing ocular toxoplasmosis (P-value = 0.04; OR = 2.20; 95% CI = 1.05-4.60), and the MICA*008~HLA-C*07 haplotype was associated with protection against the development of manifestations of ocular toxoplasmosis (P-value = 0.009; OR: 0.44; 95% CI: 0.22-0.76), these associations were not statistically significant after adjusting for multiple comparisons. MICA polymorphisms do not appear to influence the development of ocular lesions in patients diagnosed with toxoplasmosis in this study population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles*
  • Brazil
  • Female
  • Gene Frequency
  • Genotype
  • HLA-B Antigens / genetics*
  • HLA-C Antigens / genetics*
  • Haplotypes
  • Histocompatibility Antigens Class I / genetics*
  • Humans
  • Linkage Disequilibrium*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Toxoplasmosis, Ocular / diagnosis
  • Toxoplasmosis, Ocular / genetics*

Substances

  • HLA-B Antigens
  • HLA-C Antigens
  • Histocompatibility Antigens Class I
  • MHC class I-related chain A

Grants and funding

This study was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (grants: 2013/06580-9 to CMA; 2013/10050-5 to MP; 2013/15879-8 to FHAM; 2015/13723-6 to CCBM; 2013/25650-8 and 2009/17540-2 to LCM); by Fundação de Apoio à Pesquisa e Extensão de São José do Rio Preto (FAPERP) to FHAM. AVSC was supported by scholarship from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). CCBM was supported by grant from Faculdade de Medicina de São José do Rio Preto (BAP-FAMERP). LCM was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (grant: 473579/2009-0). FBF RCS APB APSC were not supported by grants. The opinions, assumptions, and conclusions or recommendations expressed in this material are the responsibility of the authors and do not necessarily reflect the views of FAPESP. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.