THE RELATIVE IMPORTANCE OF THE X-LINKED FCP LOCUS AND BETA-GLOBIN HAPLOTYPES IN DETERMINING HEMOGLOBIN-F LEVELS - A STUDY OF SS-PATIENTS HOMOZYGOUS FOR BETA(S)-HAPLOTYPES

Five factors have been hypothesized to influence the 20-fold variation in fetal haemoglobin (Hb F) levels in sickle cell anaemia (SS): age s ex, alpha-globin gene number, beta-globin haplotype, and the X-linked F-cell production locus (FCP) that regulates the production of Hb F co ntaining erythrocytes (F cells), We analysed the association of these factors with Hb F levels in 112 SS patients living in France who are h omozygous 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) w hen the FCP influence is removed, beta-globin haplotype is associated with 14% of the remaining Hb F variation, and (3) the other factors ha ve little influence, Comparison with our previous study of SS individu als in Jamaica leads to the following conclusions: (1) the X-linked FC P locus is a major determinant of Hb F levels in SS disease, (2) facto rs linked to the beta-globin haplotype have only a small effect on the variation in Hb F levels, in either the homozygous or heterozygous st ate, and (3) approximately half of the variation in Hb F levels still remains to be explained.