The role of BCL11A and HMIP-2 polymorphisms on endogenous and hydroxyurea induced levels of fetal hemoglobin in sickle cell anemia patients from southern Brazil

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• 作者：Joã ; o Ricardo Friedrisch^a ; ^b ; ^{drjrf@terra.com.br} ; Vivien Sheehan^c ; ^{vsheehan@bcm.edu} ; Jonathan M. Flanagan^c ; ^{jmflanag@txch.edu} ; Alessandro Baldan^c ; ^{alessandro.baldan@bcm.edu} ; Carly C. Ginter Summarell^c ; ^{carly.summarell@bcm.edu} ; Christina Matzembacher Bittar^b ; ^{cbittar@hcpa.edu.br} ; Bruno Kras Friedrisch^d ; ^{brunokf@gmail.com} ; Iana&ecirc ; Indiara Wilke^b ; ^{ianaewilke@bol.com.br} ; Camila Blos Ribeiro^b ; ^{camilablosribeiro@gmail.com} ; Liane Esteves Daudt^b ; ^{ldaudt@hcpa.edu.br} ; Lucia Mariano da Rocha Silla^b ; ^e ; ^{lsilla@hcpa.edu.br}
• 关键词：HbF ; fetal hemoglobin ; SCA ; sickle cell anemia ; QTL ; quantitative trait loci ; HU ; hydroxyurea ; SNP ; single nucleotide polymorphism ; MTD ; maximum tolerated dose
• 刊名：Blood Cells, Molecules, and Diseases
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：62
• 期：Complete
• 页码：32-37
• 全文大小：597 K
• 卷排序：62

文摘

High levels of fetal hemoglobin (HbF) reduce sickle cell anemia (SCA) morbidity and mortality. HbF levels vary considerably and there is a strong genetic component that influences HbF production. Genetic polymorphisms at three quantitative trait loci (QTL): Xmn1-HBG2, HMIP-2 and BCL11A, have been shown to influence HbF levels and disease severity in SCA. Hydroxyurea (HU) is a drug that increases HbF. We investigated the influence of single nucleotide polymorphisms (SNPs) at the Xmn1-HBG2 (rs7482144); BCL11A (rs1427407, rs4671393 and rs11886868); and HMIP-2 (rs9399137 and rs9402686) loci on baseline and HU-induced HbF levels in 111 HbSS patients. We found that both BCL11A and HMIP-2 were associated with increased endogenous levels of HbF. Interestingly, we also found that BCL11A was associated with higher induction of HbF with HU. This effect was independent of the effect of BCL11A on baseline HbF levels. Additional studies will be needed to validate these findings and explain the ample inter-individual variations in HbF levels at baseline and HU-induced in patients with SCA.