Meta-analysis of 2040 sickle cell anemia patients: BCL11A and HBS1L-MYB are the major modifiers of HbF in African Americans

摘要

Fetal hemoglobin (HbF) protects against many but not all of the hematologic and clinical complications of sickle cell anemia. This protection is dependent on the ability of HbF to hinder deoxyHbS polymerization. HbF level is variable and highly heritable. Previous genetic association studies found single nucleo-tide polymorphisms (SNPs) in regions of BCL11A (chromosome 2p), in the HBS1L-MYB intergenic polymorphism (HMIP; chromosome 6q), and linked to HBB (chromosome 11p) that were associated with HbF (reviewed in Akinsheye et al). Our aim was to perform a meta-analysis of genome-wide association studies (GWAS) to find genetic loci with modest effect sizes that were associated with HbF when a larger sample size was examined.