GENDER AND HAPLOTYPE EFFECTS UPON HEMATOLOGICAL MANIFESTATIONS OF ADULT SICKLE-CELL-ANEMIA

In Africa, the beta-globin gene cluster haplotype may be associated wi th variation of Hb F levels in subjects with sickle cell anemia (SS). These observations have not yet been conclusively confirmed in SS out of Africa, perhaps because of small sample sizes, the predominance of haplotype heterozygotes, and diverse influences, including gender, upo n Hb F levels. We studied 384 adult African-American SS patients (mean age, 31 years) and explored the relationship of gender, beta-globin g ene cluster haplotype, and alpha thalassemia to hematological values a nd Hb F levels. Both haplotype and gender influenced Hb F concentratio n. In the total sample, Hb F was higher in females than in males (8.2 vs. 6.5%). In 35 males who were either homozygous for the Senegal chro mosome or had the Senegal/Benin haplotype, the mean percent Hb F (8.0% ) was equivalent to the Hb F level in females with Benin and Bantu hap lotypes (similar to 7.5%). Both females and males homozygous for the S enegal haplotype chromosome or with the Senegal/Benin combination had a significant increase in Hb F compared to other groups, In 44 Senegal /Senegal or Senegal/Benin females the Hb F was 10.9%, or 1.0 g/dl, the highest value observed in all primary analysis groups, Preliminary an alyses suggested that the presence of a Bantu chromosome blunted the g ender-associated difference in Hb F, but Hb F differences between fema les with the Senegal/Benin haplotype (11.2%) and the Senegal/Bantu hap lotype (8.8%) were not statistically significant, Hemoglobin concentra tions were higher in males than in females except in subjects with at least one Senegal haplotype chromosome, where hemoglobin levels were e qual. As excpected, alpha thalassemia reduced the MCV, increased hemog lobin concentration, and lowered reticulocyte counts, regardless of ha plotype, Hb F revels were not affected by the presence of alpha thalas semia in any group. We conclude that gender and beta-globin gene clust er haplotype interact significantly in the modulation of Hb F and anem ia in adults with SS, (C) 1995 Wiley-Liss, Inc.