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

Br J Haematol. 1997 Mar;96(4):806-14. doi: 10.1046/j.1365-2141.1997.d01-2094.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Anemia, Sickle Cell / blood
  • Anemia, Sickle Cell / genetics*
  • Child
  • Child, Preschool
  • Female
  • Fetal Hemoglobin / analysis*
  • Genetic Linkage
  • Globins / genetics*
  • Haplotypes
  • Humans
  • Infant
  • Male
  • Phenotype
  • Regression Analysis
  • Reticulocytes / pathology
  • X Chromosome


  • Globins
  • Fetal Hemoglobin