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

Okumura, Jéssika Viviani; Lobo, Clarisse Lopes de Castro; Bonini-Domingos, Claudia Regina

doi:10.5581/1516-8484.20130019

LETTER TO EDITOR

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

Jéssika Viviani Okumura^I; Clarisse Lopes de Castro Lobo^II; Claudia Regina Bonini-Domingos^I

^IUniversidade Estadual Paulista "Júlio de Mesquita Filho" - UNESP, São José do Rio Preto, SP, Brazil

^IIInstituto Estadual de Hematologia Arthur de Siqueira Cavalcanti - HEMORIO, Rio de Janeiro, RJ, Brazil

^{Corresponding author} Corresponding author: Jéssika Viviani Okumura Universidade Estadual Paulista "Júlio de Mesquita Filho" (UNESP)- Instituto de Biociencias, Letras e Ciências Exatas Laboratório de Hemoglobinopatias e Genética das Doenças Hematológicas Rua Cristóvão Colombo, 2265, Jardim Nazareth 15054000 São José do Rio Preto, SP, Brazil jessika_okumura@hotmail.com

Sickle cell anemia (SCA) is defined as a monogenic disease that characterizes the homozygous state of hemoglobin S (Hb S). Hemoglobin S polymerizes under adverse conditions such as deoxygenation, acidosis or dehydration. Its polymers deform erythrocytes and lead to a diverse and complex pathophysiology^(1,2). Beta-S globin haplotypes (β^S haplotypes) are important in the comprehension of the clinical diversity of SCA patients. Five haplotypes have been associated with different ethnic groups. They are identified at specific restriction sites and named according to their region of origin and prevalence: Bantu, Benin, Senegal, Arabic-Indian(Saudi) and Cameroon⁽³⁾. This study aimed to assess the frequencies of β^S haplotypes in patients with SCA from Rio de Janeiro State, Brazil. We analyzed DNA samples from 790 patients with sickle cell disease (SCD) and classified them according to their haplotypes through an analysis of six polymorphic sites reported by Sutton et al.⁽⁴⁾. According to these authors, haplotypes that do not exhibit known digestion patterns should be classified as atypical. The polymorphic sites were evaluated by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP)^(4,5). Of the 790 patients, 527 had SCA with the following frequencies of genotyped β^S 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 total number 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 haplotypes demonstrate the influence of Western and South-Central African on the evolution of the Brazilian population⁽⁶⁾. We identified atypical haplotypes which may have originated due to genetic mechanisms such as gene conversions and the intense miscegenation between ethnic groups 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.

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Submitted: 10/24/2012

Accepted: 12/11/2012

Conflict-of-interest disclosure: The authors declare no competing financial interest

References

1. Steinberg MH. Sickle cell anemia, the first molecular disease: overview of molecular etiology, pathophysiology, and therapeutic approaches. Sci World J . 2008;8:1295-324.
2. Frenette PS, Atweh GF. Sickle cell disease: old discoveries, new concepts, and future promise. J Clin Invest. 2007;117(4):850-8.
3. Nagel RL. The origin of the hemoglobin S gene: clinical, genetic and anthropological consequences. Einstein Quart J Biol Med. 1984;2(1):53-62.
4. Sutton M, Bouhassira EE, Nagel RL. Polymerase chain reaction amplification applied to the determination of β-like globin gene cluster haplotypes. Am J Hematol. 1989;32(1):66-9.
5. Bonini-Domingos CR. Metodologias laboratoriais para o diagnóstico de hemoglobinopatias e talassemias. São José do Rio Preto: HN Editora; 2006. 121 p.
6. da Silva Filho IL, Ribeiro GS, Moura PG, Vechi ML, Cavalcante AC, de Andrada-Serpa MJ. Sickle cell disease: acute clinical manifestations in early childhood and molecular characteristics in a group of children in Rio de Janeiro. Rev Bras Hematol Hemoter. 2012;34(3):196-201.

Corresponding author:

Jéssika Viviani Okumura

Universidade Estadual Paulista "Júlio de Mesquita Filho" (UNESP)- Instituto de Biociencias, Letras e Ciências Exatas Laboratório de Hemoglobinopatias e Genética das Doenças Hematológicas

Rua Cristóvão Colombo, 2265, Jardim Nazareth

15054000 São José do Rio Preto, SP, Brazil

jessika_okumura@hotmail.com

Publication Dates

Publication in this collection
05 Apr 2013
Date of issue
2013

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. Steinberg MH. Sickle cell anemia, the first molecular disease: overview of molecular etiology, pathophysiology, and therapeutic approaches. Sci World J . 2008;8:1295-324.

[2] 2. Frenette PS, Atweh GF. Sickle cell disease: old discoveries, new concepts, and future promise. J Clin Invest. 2007;117(4):850-8.

[3] 3. Nagel RL. The origin of the hemoglobin S gene: clinical, genetic and anthropological consequences. Einstein Quart J Biol Med. 1984;2(1):53-62.

[4] 4. Sutton M, Bouhassira EE, Nagel RL. Polymerase chain reaction amplification applied to the determination of β-like globin gene cluster haplotypes. Am J Hematol. 1989;32(1):66-9.

[5] 5. Bonini-Domingos CR. Metodologias laboratoriais para o diagnóstico de hemoglobinopatias e talassemias. São José do Rio Preto: HN Editora; 2006. 121 p.

[6] 6. da Silva Filho IL, Ribeiro GS, Moura PG, Vechi ML, Cavalcante AC, de Andrada-Serpa MJ. Sickle cell disease: acute clinical manifestations in early childhood and molecular characteristics in a group of children in Rio de Janeiro. Rev Bras Hematol Hemoter. 2012;34(3):196-201.