DISSECTION OF THE ASSOCIATION STATUS OF 2 POLYMORPHISMS IN THE BETA-GLOBIN GENE-CLUSTER WITH VARIATIONS IN F-CELL NUMBER IN NONANEMIC INDIVIDUALS

Expression of fetal hemoglobin (Hb F) is under polygenic control invol ving determinants both linked and unlinked to the p-globin gene cluste r on chromosome 11. Variations in the DNase I-hypersensitive site 2 of the locus control region (LCR-HSP) and a C --> T change at position - 158 from the G gamma-gene (detected as an Xmnl polymorphism) correlate with the high level of Hb F expression in patients with sickle-cell a nemia and beta-thalassemia, Interpretation of data under these conditi ons of anemic stress is difficult because the preferential survival of Hb F-containing erythrocytes (F-cells) may not reflect the true statu s of Hb F expression, We investigated the relationship between these m arkers and Hb F expression in terms of F-cell levels in 48 unrelated n on-anemic AS heterozygotes from Sicily, The beta(S)-chromosome of all these individuals was of the Benin haplotype and they differed only by their beta(A) chromosomes, We demonstrate that F-cell expression is m ore strongly associated with LCR-HS2 polymorphism than with Xmnl polym orphism, The observed association between Xmnl polymorphism and Hb F e xpression is very likely to be due to linkage disequilibrium with LCR- HS2 sequences. (C) 1997 Wiley-Liss, Inc.