title: The relative importance of the X-linked FCP locus and beta-globin haplotypes in determining haemoglobin F levels: a study of SS patients homozygous for beta S haplotypes.
abstract: Five factors have been hypothesized to influence the 20-fold variation in fetal haemoglobin (Hb F) levels in sickle cell anaemia (SS): age sex, alpha-globin gene number, beta-globin haplotype, and the X-linked F-cell production locus (FCP) that regulates the production of Hb F containing erythrocytes (F cells). We analysed the association of these factors with Hb F levels in 112 SS patients living in France who are homozygous for the three common African beta-globin haplotypes (Benin, Bantu or Central African Republic and Senegal). We found that: (1) FCP accounts for about 40% of the overall variation in Hb F levels, (2) when the FCP influence is removed, beta-globin haplotype is associated with 14% of the remaining Hb F variation, and (3) the other factors have little influence. Comparison with our previous study of SS individuals in Jamaica leads to the following conclusions: (1) the X-linked FCP locus is a major determinant of Hb F levels in SS disease, (2) factors linked to the beta-globin haplotype have only a small effect on the variation in Hb F levels, in either the homozygous or heterozygous state, and (3)approximately half of the variation in Hb F levels still remains to be explained.
authors.affiliation: Department of Pediatrics, Johns Hopkins University, Baltimore, Maryland, USA.
authors.forename: Y P
authors.initials: YP
authors.lastname: Chang
authors.forename: M
authors.initials: M
authors.lastname: Maier-Redelsperger
authors.forename: K D
authors.initials: KD
authors.lastname: Smith
authors.forename: L
authors.initials: L
authors.lastname: Contu
authors.forename: R
authors.initials: R
authors.lastname: Ducroco
authors.forename: M
authors.initials: M
authors.lastname: de Montalembert
authors.forename: M
authors.initials: M
authors.lastname: Belloy
authors.forename: J
authors.initials: J
authors.lastname: Elion
authors.forename: G J
authors.initials: GJ
authors.lastname: Dover
authors.forename: R
authors.initials: R
authors.lastname: Girot
mesh_terms: D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005319:Fetal Hemoglobin / Q000032:analysis*; D008040:Genetic Linkage; D005914:Globins / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007223:Infant; D008297:Male; D010641:Phenotype; D012044:Regression Analysis; D012156:Reticulocytes / Q000473:pathology; D014960:X Chromosome
chemical_list: D005914:Globins; D005319:Fetal Hemoglobin