Sequence change in the HS2-LCR and Gg-globin gene promoter region of sickle cell anemia patients

Abstract

The fetal hemoglobin (HbF) levels and ß S -globin gene haplotypes of 125 sickle cell anemia patients from Brazil were investigated. We sequenced the Gγ-and Aγ-globin gene promoters and the DNase I-2 hypersensitive sites in the locus control regions (HS2-LCR) of patients with HbF level disparities as compared to their ß S haplotypes. Sixty-four (51.2%) patients had CAR/Ben genotype; 36 (28.8%) Ben/Ben; 18 (14.4%) CAR/CAR; 2 (1.6%) CAR/Atypical; 2 (1.6%) Ben/Cam; 1 (0.8%) CAR/Cam; 1 (0.8%) CAR/Arab-Indian, and 1 (0.8%) Sen/Atypical. The HS2-LCR sequence analyses demonstrated a c.-10.677G>A change in patients with the Ben haplotype and high HbF levels. The Gγ gene promoter sequence analyses showed a c.-157T>C substitution shared by all patients, and a c.-222_-225del related to the Cam haplotype. These results identify new polymorphisms in the HS2-LCR and Gγ-globin gene promoter. Further studies are required to determine the correlation between HbF synthesis and the clinical profile of sickle cell anemia patients.

Promoter region sequence differences in the A and G gamma globin genes of Brazilian sickle cell anemia patients

“…Although the age of the β Sglobin gene mutation is not known with certainty, expansion of the mutation probably occurred in parallel to malaria, a strong selective factor, becoming endemic on the African continent (16). The -157 HBG2 SNP was recently described in SCA patients from the same region of Brazil, and it was suggested that the C allele at this position may be related to HbF levels (6). In contrast to the report of Adorno et al (6), we found that 100% of healthy Afro-descendant individuals and about 90% of the SCA and reference group subjects had the variant allele for the -157 HBG2 SNP.…”

“…The regulatory sequences 5' of HBG2 and HBG1 harbor at least eight polymorphic markers. These include the 4-bp deletion (AGCA) at positions -225 to -222 upstream of HBG1 (2) and the HBG2 -157 C→T single nucleotide polymorphism (SNP), which has been reported to be associated with high HbF levels (6). Moreover, some of the HBG2 and HBG1 polymorphisms are associated with the major β S -globin gene haplotypes, which are named Benin (Ben), Central African Republic (CAR), Senegal (Sen), Arab-Indian and Cameroon (Cam), according to their geographical origin and the ethnic groups in which they are frequently found (1,7).…”