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

PLoS One. 2016 Sep 7;11(9):e0162297. doi: 10.1371/journal.pone.0162297. eCollection 2016.

Abstract

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.

MeSH terms

  • Anemia, Sickle Cell / blood*
  • Anemia, Sickle Cell / genetics*
  • Blood Vessels / pathology*
  • Brazil
  • Child
  • Child, Preschool
  • Female
  • Galectin 3 / blood*
  • Galectin 3 / genetics*
  • Genotype
  • Humans
  • Male
  • Polymorphism, Single Nucleotide / genetics*
  • Respiratory Tract Infections / blood*
  • Respiratory Tract Infections / genetics*

Substances

  • Galectin 3

Grant support

This work was supported by the National Council for Scientific and Technological Development (CNPq), the Higher Education Personnel Training Coordination (Capes) and the Foundation for Science and Technology of the State of Pernambuco (FACEPE). The funders had no role in study design, data collection, analysis, decision to publish, or preparation of the manuscript.