PLoS ONE (Jan 2016)

Single Nucleotide Polymorphisms at +191 and +292 of Galectin-3 Gene (LGALS3) Related to Lower GAL-3 Serum Levels Are Associated with Frequent Respiratory Tract Infection and Vaso-Occlusive Crisis in Children with Sickle Cell Anemia.

  • Taciana Furtado de Mendonça Belmont,
  • Kleyton Palmeira do Ó,
  • Andreia Soares da Silva,
  • Kamila de Melo Vilar,
  • Fernanda Silva Medeiros,
  • Luydson Richardson Silva Vasconcelos,
  • Ana Claudia Mendonça Dos Anjos,
  • Betânia Lucena Domingues Hatzlhofer,
  • Maíra Galdino da Rocha Pitta,
  • Marcos André Cavalcanti Bezerra,
  • Aderson da Silva Araújo,
  • Moacyr Jesus Barreto de Melo Rego,
  • Patrícia Moura,
  • Maria do Socorro Mendonça Cavalcanti

DOI
https://doi.org/10.1371/journal.pone.0162297
Journal volume & issue
Vol. 11, no. 9
p. e0162297

Abstract

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INTRODUCTION:Patients with sickle cell anemia (SCA) may present chronic hemolytic anemia, vaso-occlusion and respiratory tract infection (RTI) episodes. Galectin-3 (GAL-3) is a multifunctional protein involved in inflammation, apoptosis, adhesion and resistance to reactive oxygen species. Studies point to a dual role for GAL-3 as both a circulation damage-associated molecular pattern and a cell membrane associated pattern recognition receptor. OBJECTIVE:To investigate associations between the SNPs of GAL-3 gene (LGALS3) and serum levels with RTI and vaso-occlusive crisis (VOC) in children with SCA. MATERIALS AND METHODS:SNPs +191 and +292 in LGALS3 were studied using the TaqMan real-time PCR system; GAL-3 serum levels were measured by ELISA. The study included 79 children with SCA ranging from 2 to 12 years old. RESULTS:GAL-3 serum levels were associated with LGALS3 +191 and +292 genotypes (p <0.0001; p = 0.0169, respectively). LGALS3 +191, AA genotype was associated with low and CC with higher levels of GAL-3. For LGALS3 +292, the CC genotype was associated with lower GAL-3 and AA with higher levels. Patients with Frequency of RTI (FRTI) ≥1 presented higher frequency of +191AA (p = 0.0263) and +292AC/CC genotypes (p = 0.0320). SNP +292 was associated with Frequency of VOC (FVOC) (p = 0.0347), whereas no association was shown with SNP +191 and FVOC. However, CA/AC and AA/CC genotypes with lower GAL-3 levels showed a higher frequency in patients with FRTI ≥1 (p = 0.0170; p = 0.0138, respectively). Also, patients with FVOC ≥1 presented association with CA/AC (p = 0.0228). LGALS3 +191 and +292 combined genotypes related to low (p = 0.0263) and intermediate expression (p = 0.0245) were associated with FRTI ≥1. Lower GAL-3 serum levels were associated with FRTI ≥1 (p = 0.0426) and FVOC ≥1 (p = 0.0012). CONCLUSION:Variation of GAL-3 serum levels related to SNPs at +191 and +292 may constitute a susceptibility factor for RTI and VOC frequency.