Five factors have been hypothesized to influence the 20‐fold variation in fetal haemoglobin (Hb F) levels in sickle cell anaemia (SS): age sex, α‐globin gene number, β‐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 β‐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, β‐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 β‐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.
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