ABSTRACT
The fetal hemoglobin (HbF) levels and betaS-globin gene haplotypes of 125 sickle cell anemia patients from Brazil were investigated. We sequenced the Gg- and Ag-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 ßS haplotypes. Sixty-four (51.2 percent) patients had CAR/Ben genotype; 36 (28.8 percent) Ben/Ben; 18 (14.4 percent) CAR/CAR; 2 (1.6 percent) CAR/Atypical; 2 (1.6 percent) Ben/Cam; 1 (0.8 percent) CAR/Cam; 1 (0.8 percent) CAR/Arab-Indian, and 1 (0.8 percent) 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 Gg 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 Gg-globin gene promoter. Further studies are required to determine the correlation between HbF synthesis and the clinical profile of sickle cell anemia patients.
Subject(s)
Adult , Child , Child, Preschool , Humans , Middle Aged , Anemia, Sickle Cell/genetics , Deoxyribonuclease I/genetics , Globins/genetics , Locus Control Region/genetics , Fetal Hemoglobin/analysis , Genotype , Genetic Markers/genetics , Haplotypes , Promoter Regions, GeneticABSTRACT
ßS-Globin haplotypes were studied in 80 (160 ßS chromosomes) sickle cell disease patients from Salvador, Brazil, a city with a large population of African origin resulting from the slave trade from Western Africa, mainly from the Bay of Benin. Hematological and hemoglobin analyses were carried out by standard methods. The ßS-haplotypes were determined by PCR and dot-blot techniques. A total of 77 (48.1 percent) chromosomes were characterized as Central African Republic (CAR) haplotype, 73 (45.6 percent) as Benin (BEN), 1 (0.63 percent) as Senegal (SEN), and 9 (5.63 percent) as atypical (Atp). Genotype was CAR/CAR in 17 (21.3 percent) patients, BEN/BEN in 17 (21.3 percent), CAR/BEN in 37 (46.3 percent), BEN/SEN in 1 (1.25 percent), BEN/Atp in 1 (1.25 percent), CAR/Atp in 6 (7.5 percent), and Atp/Atp in 1 (1.25 percent). Hemoglobin concentrations and hematocrit values did not differ among genotype groups but were significantly higher in 25 patients presenting percent fetal hemoglobin ( percentHbF) > or = 10 percent (P = 0.002 and 0.003, respectively). The median HbF concentration was 7.54 ± 4.342 percent for the CAR/CAR genotype, 9.88 ± 3.558 percent for the BEN/BEN genotype, 8.146 ± 4.631 percent for the CAR/BEN genotype, and 4.180 ± 2.250 percent for the CAR/Atp genotype (P = 0.02), although 1 CAR/CAR individual presented an HbF concentration as high as 15 percent. In view of the ethnic and geographical origin of this population, we did not expect a Hardy-Weinberg equilibrium for CAR/CAR and BEN/BEN homozygous haplotypes and a high proportion of heterozygous CAR/BEN haplotypes since the State of Bahia historically received more slaves from Western Africa than from Central Africa
Subject(s)
Humans , Male , Female , Anemia, Sickle Cell , Fetal Hemoglobin , Globins , Haplotypes , Anemia, Sickle Cell , Benin , Brazil , Central African Republic , Fetal Hemoglobin , Genotype , Immunoblotting , Polymerase Chain Reaction , SenegalABSTRACT
Sickle cell disease has a worldwide distribution and is a public health problem in Brazil. Although vaso-occlusive crisis (VOC) is one of the most important clinical features of the disease, there are still several steps of its pathogenesis which are unknown. The increase of the chemotactic factor interleukin 8 (IL-8) has been reported to be involved in sickle cell disease crisis, but this has not been demonstrated conclusively. In the present study we analyzed serum IL-8 levels by ELISA and hematological parameters and hemoglobin patterns by standard techniques in 23 (21 SS and 2 SC) Brazilian patients with sickle cell syndromes during VOC caused by different inducing factors, 22 (21 SS and 1 SC) sickle cell patients out of crisis, and 11 healthy controls. Increased IL-8 levels were observed in 19 of 23 VOC patients (79.2 percent), 3 of them with more than 1,000 pg/ml. Seventeen of 22 (77.3 percent) non-crisis patients showed low IL-8 levels (less than 15 pg/ml). Healthy controls had low IL-8 levels. A significant difference in serum IL-8 levels was observed between crisis and non-crisis sickle cell patients (P<0.0001). There was no correlation between IL-8 levels and hematological data or hemoglobin patterns. High serum IL-8 levels were observed in VOC patients independently of the crisis-inducing factor. We conclude that in the studied population, IL-8 concentration may be a useful VOC marker, although the mechanism of the pathogenic process of sickle cell VOC syndromes remains unclear