title: Genetic variants associated with fetal hemoglobin levels show the diverse ethnic origin in Colombian patients with sickle cell anemia.
abstract: BACKGROUND
  Fetal hemoglobin is an important factor in modulating the severity of sickle cell anemia. Its level in peripheral blood underlies strong genetic determination. Associated loci with increased levels of fetal hemoglobin display population-specific allele frequencies.
  
  
  OBJECTIVE
  We investigated the presence and effect of known common genetic variants promoting fetal hemoglobin persistence (rs11886868, rs9399137, rs4895441, and rs7482144) in 60 Colombian patients with sickle cell anemia.
  
  
  METHODS
  Four single nucleotide polymorphisms (SNP) were genotyped by restriction fragment length polymorphisms (RFLP) and the use of the TaqMan procedure. Fetal hemoglobin (HbF) from these patients was quantified using the oxyhemoglobin alkaline denaturation technique. Genotype frequencies were compared with frequencies reported in global reference populations.
  
  
  RESULTS
  We detected genetic variants in the four SNPs, reported to be associated with higher HbF levels for all four SNPs in the Colombian patients. Genetic association between SNPs and HbF levels did not reach statistical significance. The frequency of these variants reflected the specific ethnic make-up of our patient population: A high prevalence of rs7482144-'A' reflects the West-African origin of the sickle cell mutation, while high frequencies of rs4895441-'G' and rs11886868-'C' point to a significant influence of an Amerindian ethnic background in the Colombian sickle cell disease population.
  
  
  CONCLUSIONS
  These results showed that in the sickle cell disease population in Colombia there is not a unique genetic background, but two (African and Amerindian). This unique genetic situation will provide opportunities for a further study of these loci, such as fine-mapping and molecular-biological investigation. Colombian patients are expected to yield a distinctive insight into the effect of modifier loci in sickle cell disease.
authors: Grupo de Genética Molecular Humana, Sección de Genética, Departamento de Biología, Universidad del Valle.
authors: Cristian
authors: C
authors: Fong
authors: King's College London, School of Medicine, The James Black Centre, , London, England, United Kingdom.
authors: Stephan
authors: S
authors: Menzel
authors: Grupo de Genética Molecular Humana, Sección de Genética, Departamento de Biología, Universidad del Valle.
authors: María Alejandra
authors: MA
authors: Lizarralde
authors: Grupo de Genética Molecular Humana, Sección de Genética, Departamento de Biología, Universidad del Valle.
authors: Guillermo
authors: G
authors: Barreto
mesh_terms: D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D044383:Black People / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003105:Colombia / Q000453:epidemiology; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D005319:Fetal Hemoglobin / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007199:Indians, South American / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci / Q000235:genetics*; D012097:Repressor Proteins; D012675:Senegal / Q000208:ethnology; D012807:Sierra Leone / Q000208:ethnology; D055815:Young Adult; D055545:gamma-Globins / Q000235:genetics*
chemical_list: C486563:BCL11A protein, human; D002352:Carrier Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D055545:gamma-Globins; D005319:Fetal Hemoglobin