Main Article Content
Alpha Thalassemia, Iron Treatment, Amazonas, Brazil
Background: Alpha Thalassemia (a-thal) is a heterogeneous group of hereditary alterations caused by deletions that affect alpha regulatory genes and the 3.7Kb deletion is the most frequent worldwide. In Brazil, the prevalence ranges from 20% and 35%, depending mainly on race, being more predominant in Afro-descendants. Purpose: The aim was to determine ?-thal -?3.7Kb and -?4.2Kb deletions, estimating their frequency in individuals from five regions of Amazon. Methods: Volunteers (individuals >18 years old, of both genders) blood samples (n=1809) were collected from march 2014 to september 2017, at hospitals and/or health centers of each participant city. Alpha Thalassemia 3.7Kb genotyping was performed by GAP-PCR, while 4.2Kb deletion by Multiplex-PCR. The studied population included: Manaus (capital), 356 (19.7%) samples; Iranduba 232 (12.8%); Manacapuru, 287 (15.9%); Presidente Figueiredo, 370 (20.5%); Itacoatiara, 301 (16.6%); and Coari, 263 (14.5%). Results: The average age among males was 35.3±14.8, while for females it was 36.7±14.9 years old. Alpha Thalassemia was diagnosed in 143 individuals (7.9%) and all of these individuals carried the 3.7Kb deletion, 5.95% in heterozygosis and 1.95% in homozygosis. The associations analyses to the a-thal genotypes were statistically significant for all hematological parameters (p<.001), except serum iron and serum ferritin analyses among carriers ?-thal. Microcytosis (MCV <80fL) was found in 158 individuals (8,46%). Conclusion: The alfa-thal prevalence corroborates with other Brazilians studies. Molecular diagnosis is important to prevent the most severe forms of the disease, thus epidemiological studies using molecular tools become extremely important in regions where the disease is underestimated. In this context, this is the first study that reports ?-thalassemia deletion in the population from State of Amazonas. Our findings are relevant because they have impact in the clinical therapeutic choice and also demonstrate the importance of differential diagnosis between genetic anemia and iron deficiency anemia.
2. Sakai Y, Kobayashi S, Shibata H, Furuumi H, Endo T, Fucharoen S, Hamano S, Acharya GP, Kawasaki T, Fukumaki Y. Molecular analysis of alpha-thalassemia in Nepal: correlation with malaria endemicity. J Hum Genet. 2000;45(3):127-32.
3. Koza K. Hemoglobinopathies and thalasemias - genetic basis and molecular diagnosis. 2012;(7):589–94.
4. P. Ponka, M.J. Koury, A.D. Sheftel. Erythropoiesis, hemoglobin synthesis, and erythroid mitochondrial iron homeostasis. G.C. Ferreira, K.M. Kadish, K.M. Smith, R. Guilard (Eds.), Handbook of Porphyrin Science, World Scientific Co., Singapore (2013), pp. 41-84.
5. Goh SH1, Lee YT, Bhanu NV, Cam MC, Desper R, Martin BM, Moharram R, Gherman RB, Miller JL. A newly discovered human globin gene. Blood. 2005 Aug 15;106(4):1466-72. Epub 2005 Apr 26.
6. Higgs DR, Weatherall DJ. The Alpha Thalassaemias. Cell Mol Life Sci. 2009;66(7):1154–62.
7. D OTTO, FRC.; SILVA, JEP. Talassemias Alfa e Beta: Revisão. Trabalho apresentado ao curso de Pós Graduação em Nível de Especialização. Centro de Ciências da Saúde, Universidade Federal de Santa Maria –(Especialização).Santa Maria, 37f., 2005.
8. Kasper, Dennis L., Anthony S. Fauci, Stephen L. Hauser, Dan L. Longo, J. Larry Jameson, and Joseph Loscalzo. eds. Harrison's Principles of Internal Medicine, 18e. New York, NY: McGraw-Hill; 2015.
9. Spier C. Wintrobe?s Atlas of Clinical Hematology. Am J Surg Pathol. 2008;32:1428.
10. Higgs DR, Goodbourn SE, Lamb J, Clegg JB, Weatherall DJ, Proudfoot NJ. Alpha-Thalassemia caused by a polyadenylation signal mutation. Nature. 1983 Nov 24-30;306(5941):398-400.
11. Harteveld CL, Higgs DR. Alpha-thalassaemia. Orphanet J Rare Dis. 2010 May 28;5:13.
12. Ribeiro DM, Sonati MF. Regulation of human alpha-globin gene expression and alpha-thalassemia. Genet Mol Res. 2008 Oct 14;7(4):1045-53.
13. Hardison RC. (2012) Evolution of hemoglobin and its genes. Cold Spring Harb Perspect Med. 2:a011627. doi: 10.1101/cshperspect.a011627. PubMed PMID:23209182. PMCID: PMC3543078.
14. Li CK. New trend in the epidemiology of thalassaemia. Best Pract Res Clin Obstet Gynaecol. 2017 Feb;39:16-26.
15. Baysal E. Huisman TJH. Detection of common deletional ?-thalassemia-2 determinants by PCR. Am J Hematol. 1994;46(3):208–13.
16. Tan AS, Quah TC, Low PS, Chong SS. A rapid and reliable 7-deletion multiplex polymerase chain reaction assay for a-thalassemia. Blood, vol. 98, no. 1, pp. 250-251, 2001.
17. GOOGLE, INC. Google Maps. Available in: http://code.google.com/apis/maps/documentation/directions/ Accessed on: March 2020.
18. Cürük MA1, Kilinç Y, Evrüke C, Ozgünen FT, Aksoy K, Yüre?ir GT. Prenatal diagnosis of Hb H disease caused by a homozygosity for the ?2 polyA mutation. Hemoglobin. 2001 May;25(2):255-8
19. Karen DF. Clinical evaluation of hemoglobinopathies: Part I. Thalassemia. The Warde Medical Laboratory Article Archives. 2003, Volume 14, Number 2.
20. Foglietta E1, Deidda G, Graziani B, Modiano G, Bianco I. Detection of ?-globin gene disorders by a simple PCR methodology. Haematologica. 1996 Sep-Oct;81(5):387-96.
21. Wagner SC, Silvestri MC, Bittar CM, Friedrisch JR, Silla LMR, Para C. Prevalence of thalassemias and variant hemoglobins in patients with non-ferropenic anemia. bras hematol hemoter. 2005;27(1):37–42.
22. WHO. Thalassaemia and other haemoglobinopathies. 2006. http://apps.who.int/gb/archive/pdf_files/EB118/B118_5-en.pdf (Acesso em 20/01/2019).
23. Sankar VH, Arya V, Tewari D, Gupta UR, Pradhan M, Agarwal S. Genotyping of alpha-thalassemia in microcytic hypochromic anemia patients from North India. J Appl Genet. 2006;47(4):391-5.
24. Lois R. Manning, J. Eric Russell, Julio C. Padovan, Brian T. Chait, Anthony Popowicz, Robert S. Manning, and James M. Manning. Human embryonic, fetal, and adult hemoglobins have different subunit interface strengths. Correlation with lifespan in the red cell. Protein Sci. 2007 Aug; 16(8): 1641–1658.
25. Karamzade A, Mirzapour H, Hoseinzade M, Asadi S, Gholamrezapour T, Tavakoli P, Salehi M. ?-Globin Gene Mutations in Isfahan Province, Iran. Int. J. Hemoglobin. Res. 2014;38(3).
26. Amaz RV. Revista Veredas Amazônicas – Nov – no 01, vol i, 2011. issn: 2237- 4043. 2011;I(V).
27. Jakob AAE. International migration in the Brazilian Amazon. Toledo Vol. 15, Ed. 3, (2011): 422-442.
28. Xavier FCC. Migrações Internacionais na Amazônia Brasileira: Impactos na Política Migratória e na Política Externa. 2012. http://repositorio.unb.br/bitstream/10482/10739/1/2012_Fernando%20Cesar%20Costa%20Xavier.pdf
29. Jakob AAE. The recent international migration in the Brazilian Amazon. REMHU, Rev. Interdiscip. Mobil. Hum. vol.23 no.45 Brasília July/Dec. 2015.
30. Osório, Rafael Guerreiro. O Sistema Classificatório de Cor ou Raça do IBGE. Brasília, nov.2003. Disponível em: http://www.ipea.gov.br/portal/index.php? option=com_content&view=article&id=4212. Acesso em março 2019
31 .Petruccelli, José Luís & Saboia, Ana Lucia(org.).Características Étnico-Raciais da População. IBGE,2013.
32. Nunes D, Galvani CM, Pegoraro PP, Sucena TA, Barril N. Prevalence and Epidemiological Aspects of Patients with Hemoglobinopathies in a Genetic Counseling Outpatient Clinic. CuidArte, Enferm ; 11(1): 100-103, jan.2017.
33. Borges E, Wenning MR, Kimura EM, Gervásio SA, Costa FF, Sonati MF. High prevalence of alpha-thalassemia among individuals with microcytosis and hypochromia without anemia. Braz J Med Biol Res. 2001 Jun;34(6):759-62.
34. Carlos AM, Souza RA, Souza BM, Pereira Gde A, Tostes Júnior S, Martins PR, Moraes-Souza H. Hemoglobinopathies in newborns in the southern region of the Triângulo Mineiro, Brazil. Cross-sectional study. Sao Paulo Medical Journal = Revista Paulista de Medicina, 31 Aug 2015, 133(5):439-444.
35. Adorno EV, Couto FD, Moura Neto JP, Menezes JF, Rêgo M, Reis MG, Gonçalves MS.. Hemoglobinopathies in newborns from Salvador, Bahia, Northeast Brazil. Cad Saude Publica. 2005 Jan-Feb;21(1):292-8. Epub 2005 Jan 28.