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.
BACKGROUND
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.


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).


CONCLUSIONS
Variation of GAL-3 serum levels related to SNPs at +191 and +292 may constitute a susceptibility factor for RTI and VOC frequency.
Programa de Doutorado da Rede Nordeste de Biotecnologia, Recife, Brasil.
Taciana Furtado de
TF
Mendonça Belmont
Instituto de Ciências Biológicas e Faculdade de Ciências Médicas, Universidade de Pernambuco, Recife, Brasil.
Kleyton Palmeira
KP
do Ó
Instituto de Ciências Biológicas e Faculdade de Ciências Médicas, Universidade de Pernambuco, Recife, Brasil.
Andreia
A
Soares da Silva
Laboratório de Imunomodulação e Novas Abordagens Terapêutica (LINAT), Universidade Federal de Pernambuco, Recife, Brasil.
Kamila
K
de Melo Vilar
Instituto de Ciências Biológicas e Faculdade de Ciências Médicas, Universidade de Pernambuco, Recife, Brasil.
Fernanda
F
Silva Medeiros
Centro de Pesquisas Aggeu Magalhães, CPqAM-FIOCRUZ-PE, Recife, State of Pernambuco, Brazil.
Luydson Richardson
LR
Silva Vasconcelos
Fundação Hematologia e Hemoterapia de Pernambuco (HEMOPE), Recife, Brasil.
Ana Claudia
AC
Mendonça Dos Anjos
Departamento de Ciências Biológicas, Universidade Federal de Pernambuco, Recife, Brasil.
Betânia Lucena
BL
Domingues Hatzlhofer
Laboratório de Imunomodulação e Novas Abordagens Terapêutica (LINAT), Universidade Federal de Pernambuco, Recife, Brasil.
Maíra Galdino da Rocha
MG
Pitta
Departamento de Ciências Biológicas, Universidade Federal de Pernambuco, Recife, Brasil.
Marcos André Cavalcanti
MA
Bezerra
Fundação Hematologia e Hemoterapia de Pernambuco (HEMOPE), Recife, Brasil.
Aderson da Silva
Ada S
Araújo
Laboratório de Imunomodulação e Novas Abordagens Terapêutica (LINAT), Universidade Federal de Pernambuco, Recife, Brasil.
Moacyr Jesus Barreto
MJ
de Melo Rego
Programa de Doutorado da Rede Nordeste de Biotecnologia, Recife, Brasil.|Instituto de Ciências Biológicas e Faculdade de Ciências Médicas, Universidade de Pernambuco, Recife, Brasil.
Patrícia
P
Moura
Programa de Doutorado da Rede Nordeste de Biotecnologia, Recife, Brasil.|Instituto de Ciências Biológicas e Faculdade de Ciências Médicas, Universidade de Pernambuco, Recife, Brasil.
Maria do Socorro Mendonça
Mdo S
Cavalcanti
D000755:Anemia, Sickle Cell / Q000097:blood* / Q000235:genetics*; D001808:Blood Vessels / Q000473:pathology*; D001938:Brazil; D002648:Child; D002675:Child, Preschool; D005260:Female; D037502:Galectin 3 / Q000097:blood* / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012141:Respiratory Tract Infections / Q000097:blood* / Q000235:genetics*
D037502:Galectin 3