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Genetic variants associated with white blood cell count amongst individuals with sickle cell disease.
Cintho Ozahata, Mina; Guo, Yuelong; Gomes, Isabel; Malta, Barbara; Belisário, André; Amorim, Luiz; Teles, Dahra; Park, Miriam; Kelly, Shannon; Sabino, Ester C; Page, Grier P; Custer, Brian; Dinardo, Carla L.
Afiliación
  • Cintho Ozahata M; University of São Paulo, São Paulo, Brazil.
  • Guo Y; RTI International, Atlanta, Georgia, USA.
  • Gomes I; Federal University of Minas Gerais, Minas Gerais, Brazil.
  • Malta B; Fundação Hemominas, Belo Horizonte, Minas Gerais, Brazil.
  • Belisário A; Fundação Hemominas, Belo Horizonte, Minas Gerais, Brazil.
  • Amorim L; HEMORIO, Rio de Janeiro, Brazil.
  • Teles D; Fundação HEMOPE, Recife, Pernambuco, Brazil.
  • Park M; Children Institute-University of São Paulo, São Paulo, Brazil.
  • Kelly S; BCHO - UCSF Benioff Children's Hospital Oakland, Oakland, California, USA.
  • Sabino EC; University of São Paulo, São Paulo, Brazil.
  • Page GP; RTI International, Atlanta, Georgia, USA.
  • Custer B; Vitalant Research Institute, San Francisco, California, USA.
  • Dinardo CL; Fundação Pró-Sangue, São Paulo, Brazil.
Br J Haematol ; 2024 Sep 15.
Article en En | MEDLINE | ID: mdl-39279196
ABSTRACT

BACKGROUND:

Sickle cell disease (SCD) is a Mendelian disorder characterized by a point mutation in the ß-globin gene that leads to sickling of erythrocytes. Several studies have shown that absolute neutrophil count is strongly associated with clinical severity of SCD, suggesting an apparent role of white blood cells (WBC) in SCD pathology. However, the mechanism by which genetic variants lead to WBC count differences in SCD patients remains unclear.

METHODS:

Genome-wide association (GWA) analyses were carried out amongst a cohort of 2409 Brazil SCD participants. Association of WBC count and genetic markers were investigated in homozygous sickle cell anaemia participants and compound heterozygous sickle cell haemoglobin C participants.

RESULTS:

GWA analysis showed that variants in genes TERT, ACKR1, and FAM3C are associated with WBC count variation. The well-studied association between WBC count and Duffy null phenotype (variant in ACKR1) in healthy populations was replicated, reinforcing the influence of the SNP rs2814778 (T>C) in WBC count.

CONCLUSION:

Genetics plays an important role in regulating WBC count in patients with SCD. Our results point to possible mechanisms involved in WBC count variation and as increased WBC count is associated with more severe SCD, these results could suggest potential therapeutic targets for individuals with SCD.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Br J Haematol Año: 2024 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Br J Haematol Año: 2024 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Reino Unido