Genetic variants associated with white blood cell count amongst individuals with sickle cell disease.
GWAS
WBC
sickle cell disease
Journal
British journal of haematology
ISSN: 1365-2141
Titre abrégé: Br J Haematol
Pays: England
ID NLM: 0372544
Informations de publication
Date de publication:
15 Sep 2024
15 Sep 2024
Historique:
received:
14
05
2024
accepted:
27
08
2024
medline:
16
9
2024
pubmed:
16
9
2024
entrez:
16
9
2024
Statut:
aheadofprint
Résumé
Sickle cell disease (SCD) is a Mendelian disorder characterized by a point mutation in the β-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. 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. 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. 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.
Sections du résumé
BACKGROUND
BACKGROUND
Sickle cell disease (SCD) is a Mendelian disorder characterized by a point mutation in the β-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
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
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
CONCLUSIONS
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.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NHLBI NIH HHS
ID : HHSN2682011#x2010;00001I
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN2682011#x2010;00002I
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN2682011#x2010;00003I
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN2682011#x2010;00004I
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN2682011#x2010;00005I
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN2682011#x2010;00006I
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN2682011#x2010;00007I
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN2682011#x2010;00008I
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN2682011#x2010;00009I
Pays : United States
Organisme : NHLBI NIH HHS
ID : HHSN268201500015C
Pays : United States
Informations de copyright
© 2024 British Society for Haematology and John Wiley & Sons Ltd.
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