Department of Chemistry

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Browsing Department of Chemistry by Author "Allman, Marlene"

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    g(HbF): a genetic model of fetal hemoglobin in sickle cell disease.
    (Blood advances., 2018) Gardner, Kate; Fulford, Tony; Silver, Nicholas; Rooks, Helen; Angelis, Nikolaos; Allman, Marlene; Nkya, Siana; Makani, Julie; Howard, Jo; Kesse-Adu, Rachel; Rees, David C; Stuart-Smith, Sara; Yeghen, Tullie; Awogbade, Moji; Sangeda, Raphael; Mgaya, Josephine; Patel, Hamel; Newhouse, Stephen; Menzel, Stephan; Thein, Swee L
    Fetal hemoglobin (HbF) is a strong modifier of sickle cell disease (SCD) severity and isassociated with 3 common genetic loci. Quantifying the genetic effects of the 3 loci wouldspecifically address the benefits of HbF increases in patients. Here, we have applied statisticalmethods using the most representative variants:rs1427407andrs6545816inBCL11A,rs66650371(3-bp deletion) andrs9376090inHMIP-2A,rs9494142andrs9494145inHMIP-2B,andrs7482144(Xmn1-HBG2in theb-globin locus) to createg(HbF), a genetic quantitativevariable for HbF in SCD. Only patients aged$5 years with complete genotype and HbFdata were studied. Five hundred eighty-one patients with hemoglobin SS (HbSS) or HbSb0thalassemia formed the“discovery”cohort. Multiple linear regression modeling rational-ized the 7 variants down to 4 markers (rs6545816,rs1427407,rs66650371, andrs7482144)eachindependentlycontributing HbF-boosting alleles, together accounting for 21.8% of HbFvariability (r2) in the HbSS or HbSb0patients. The model was replicated with consistentr2in 2 different cohorts: 27.5% in HbSC patients (N5186) and 23% in 994 Tanzanian HbSSpatients.g(HbF), our 4-variant model, provides a robust approach to account for the geneticcomponent of HbF in SCD and is of potential utility in sickle genetic and clinical studies