Genetic variants at HbF-modifier loci moderate anemia and leukocytosis in sickle cell disease in Tanzania


Mtatiro, SN; Makani, J; Mmbando, B; Thein, SL; Menzel, S; Cox, SE; (2014) Genetic variants at HbF-modifier loci moderate anemia and leukocytosis in sickle cell disease in Tanzania. American journal of hematology, 90 (1). E1-E4. ISSN 0361-8609 DOI: https://doi.org/10.1002/ajh.23859

[img]
Preview
Text - Published Version
License:

Download (632kB) | Preview

Abstract

Fetal hemoglobin (HbF) is a recognized modulator of sickle cell disease (SCD) severity. HbF levels are strongly influenced by genetic variants at three major genetic loci, Xmn1-HBG2, HMIP-2, and BCL11A, but the effect of these loci on the hematological phenotype in SCD, has so far not been investigated. In a cohort of individuals with SCD in Tanzania (HbSS and HbS/β° thalassemia, n = 726, aged 5 or older), HbF levels were positively correlated with hemoglobin, red blood cell (RBC) indices, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH), and negatively with white blood cell (WBC) and platelet counts (all P < 0.0001). We subsequently assessed the contribution of the three HbF modifier loci and detected diverse effects, including a reduction in anemia, leukocytosis, and thrombocytosis associated with certain HbF-promoting alleles. The presence of the 'T' allele at Xmn1-HBG2 led to a significant increase in hemoglobin (P = 9.8 × 10(-3) ) but no changes in cellular hemoglobin content. Xmn1-HBG2 'T' also has a weak effect decreasing WBC (P = 0.06) and platelet (P = 0.06) counts. The BCL11A variant (rs11886868-'C') increases hemoglobin (P = 2 × 10(-3) ) and one of the HBS1L-MYB variants decreases WBC values selectively (P = 2.3 × 10(-4) ). The distinct pattern of effects of each variant suggests that both, disease alleviation through increased HbF production, and 'pleiotropic' effects on blood cells, are involved, affecting a variety of pathways.

Item Type: Article
Keywords: Adolescent, Adult, Alleles, Anemia, blood, genetics, Anemia, Sickle Cell, blood, genetics, Child, Child, Preschool, Female, Fetal Hemoglobin, genetics, Genetic Loci, Hemoglobins, analysis, Heterozygote, Homozygote, Humans, Leukocyte Count, Leukocytosis, genetics, Male, Polymorphism, Single Nucleotide, Regression Analysis, Severity of Illness Index, Tanzania, Young Adult
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Population Health (2012- ) > Dept of Nutrition and Public Health Interventions Research (2003-2012)
Faculty of Epidemiology and Population Health > Dept of Population Health (2012- )
PubMed ID: 25263325
Web of Science ID: 346771400001
URI: http://researchonline.lshtm.ac.uk/id/eprint/2124179

Statistics


Download activity - last 12 months
Downloads since deposit
190Downloads
309Hits
Accesses by country - last 12 months
Accesses by referrer - last 12 months
Impact and interest
Additional statistics for this record are available via IRStats2

Actions (login required)

Edit Item Edit Item