Dissection of the association status of two polymorphisms in the β-globin gene cluster with variations in F-cell number in non-anemic individuals

✍ Scribed by Merghoub, Taha; Perichon, Bruno; Maier-Redelsperger, Micheline; Dibenedetto, Salvatore Pietro; Samperi, Piera; Ducrocq, Rolande; Feingold, Nicole; Elion, Jacques; Schiliro, Gino; Labie, Dominique; Krishnamoorthy, Rajagopal

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 61 KB
• Volume: 56
• Category: Article
• ISSN: 0361-8609
• DOI: 10.1002/(sici)1096-8652(199712)56:4<239::aid-ajh7>3.0.co;2-y

✦ Synopsis

Expression of fetal hemoglobin (Hb F) is under polygenic control involving determinants both linked and unlinked to the beta-globin gene cluster on chromosome 11. Variations in the DNase I-hypersensitive site 2 of the locus control region (LCR-HS2) and a C --> T change at position -158 from the Ggamma-gene (detected as an XmnI polymorphism) correlate with the high level of Hb F expression in patients with sickle-cell anemia and beta-thalassemia. Interpretation of data under these conditions of anemic stress is difficult because the preferential survival of Hb F-containing erythrocytes (F-cells) may not reflect the true status of Hb F expression. We investigated the relationship between these markers and Hb F expression in terms of F-cell levels in 48 unrelated non-anemic AS heterozygotes from Sicily. The betaS-chromosome of all these individuals was of the Benin haplotype and they differed only by their betaA chromosomes. We demonstrate that F-cell expression is more strongly associated with LCR-HS2 polymorphism than with XmnI polymorphism. The observed association between XmnI polymorphism and Hb F expression is very likely to be due to linkage disequilibrium with LCR-HS2 sequences.