Beta-S globin haplotypes in patients with sickle cell anemia: one approach to understand the diversity in Brazil.

Sickle cell anemia (SCA) is defined as a monogenic disease that characterizes thehomozygous state of hemoglobin S (Hb S). Hemoglobin S polymerizes under adverse conditionssuch as deoxygenation, acidosis or dehydration. Its polymers deform erythrocytes and leadto a diverse and complex pathophysiology(. Beta-S globin haplotypes (βS haplotypes) areimportant in the comprehension of the clinical diversity of SCA patients. Five haplotypes havebeen associated with different ethnic groups. They are identified at specific restriction sites andnamed according to their region of origin and prevalence: Bantu, Benin, Senegal, Arabic-Indian(Saudi) and Cameroon(. This study aimed to assess the frequencies of βS haplotypes in patientswith SCA from Rio de Janeiro State, Brazil. We analyzed DNA samples from 790 patients withsickle cell disease (SCD) and classified them according to their haplotypes through an analysisof six polymorphic sites reported by Sutton et al.(. According to these authors, haplotypes thatdo not exhibit known digestion patterns should be classified as atypical. The polymorphic sites were evaluated by polymerase chain reaction (PCR) followed by restriction fragment lengthpolymorphism (RFLP)(. Of the 790 patients, 527 had SCA with the following frequencies of genotyped βS haplotypes: 295 (56.0%) Bantu/Bantu; 128 (24.3%) Bantu/Benin; 44 (8.3%)Bantu/Atypical; 36 (6.84%) Benin/Benin; 10 (1.9%) Benin/Atypical; three (0.57%) Bantu/Cameroon; three (0.57%) Benin/Cameroon; three (0.57%) Atypical/Atypical; two (0.38%)Bantu/Saudi; two (0.38%) Bantu/Senegal and one (0.19%) Benin/Saudi. From the totalnumber of 1054 chromosomes analyzed, 769 (72.96%) were identified with the Bantu allele according to the allelic frequency evaluation; 214 (20.3%) Benin; 60 (5.7%) Atypical; six(0.57%) Cameroon; three (0.28%) Saudi and two (0.19%) Senegal. Data from genotype and allele frequencies are shown in Table 1. The high frequencies of Bantu and Benin haplotypesdemonstrate the influence of Western and South-Central African on the evolution of the Brazilian population(. We identified atypical haplotypes which may have originated due togenetic mechanisms such as gene conversions and the intense miscegenation between ethnicgroups that inhabit Rio de Janeiro State and Brazil. We emphasize the need of identifying and characterizing these genetic variations in order to better understand the clinical aspects and phenotypic diversity found in Brazilian SCD patients.

Table 1

Allelic and genotypic frequency of beta-S globin haplotypes

Haplotype βS/ βS	Genotypic frequency n (%)	Haplotype globin βS	Allelic frequency n (%)
Total	527 (100)		1054 (100)
Bantu/Bantu	295 (56)	Bantu	769 (72.96)
Bantu/Benin	128 (24.3)	Benin	214 (20.3)
Bantu/Atypical	44 (8.3)	Atypical	60 (5.7)
Benin/Benin	36 (6.84)	Cameroon	6 (0.57)
Benin/Atypical	10 (1.9)	Saudi	3 (0.28)
Bantu/Cameroon	3 (0.57)	Senegal	2 (0.19)
Benin/Cameroon	3 (0.57)
Atypical/Atypical	3 (0.57)
Bantu/Saudi	2 (0.38)
Bantu/Senegal	2 (0.38)
Benin/Saudi	1 (0.19)

βS: beta-S globin

Genotype Frequency: number of individuals with respective haplotype

Allele Frequency: number of chromosomes with respective haplotype