Polymorphisms in genes that affect the variation of lipid levels in a Brazilian pediatric population with sickle cell disease: rs662799 APOA5 and rs964184 ZPR1

Blood Cells Mol Dis. 2020 Feb;80:102376. doi: 10.1016/j.bcmd.2019.102376. Epub 2019 Oct 22.


This cross-sectional study investigated associations between SNPs in metabolizing lipid genes, alpha-thalassemia and laboratory parameters in two forms of sickle cell disease (SCD), sickle cell anemia (SCA) and hemoglobin SC disease (HbSC) in a pediatric population. Among the groups SCA and HbSC was found a higher proportion of increased triglycerides (TG) in SCA. High levels of TG were significantly associated with lower hemoglobin (p = 0.006) and HDL-C (p = 0.037), higher white blood cell count (p = 0.027), LDH (p = 0.004) and bilirubins (p < 0.05) in SCD. Patients with HDL-C ≤40 mg/dL had higher markers hemolytic levels. Therapy of HU significantly influenced several hematological and biochemical parameters but not lipid fractions. Genotypes of the APOA5 rs662799 were not associated with lipid levels. The G-risk allele rs964184/ZPRI ZNF259/ZPR1 gene (GC + GG genotypes) was associated with increased levels of TG in children ≥10 years old (p = 0.045) and the atherogenic ratio TG/HDL-C (p = 0.032) in SCD. The use of HU improves levels of hemolysis and inflammation markers in SCD with high TG and, while not interfering with lipid levels, seems to overlap the effect of the G-risk allele in on them. This study reported for the first time that rs964184 SNP could be a genetic modifier of TG in SCD.

Keywords: APOA5; Hemoglobin SC disease; Sickle cell anemia; Sickle cell disease; ZNF259; ZPR1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Alleles
  • Anemia, Sickle Cell / blood*
  • Anemia, Sickle Cell / epidemiology
  • Anemia, Sickle Cell / genetics*
  • Apolipoprotein A-V / genetics*
  • Biomarkers
  • Blood Cell Count
  • Blood Chemical Analysis
  • Brazil / epidemiology
  • Child
  • Cross-Sectional Studies
  • Female
  • Genetic Association Studies*
  • Genotype
  • Hemoglobin SC Disease / blood
  • Hemoglobin SC Disease / epidemiology
  • Hemoglobin SC Disease / genetics
  • Humans
  • Lipids / blood*
  • Male
  • Membrane Transport Proteins / genetics*
  • Middle Aged
  • Phenotype
  • Polymorphism, Genetic*
  • Polymorphism, Single Nucleotide
  • Population Surveillance
  • Young Adult


  • APOA5 protein, human
  • Apolipoprotein A-V
  • Biomarkers
  • Lipids
  • Membrane Transport Proteins
  • ZPR1 protein, human