Alpha thalassemia, but not β(S)-globin haplotypes, influence sickle cell anemia clinical outcome in a large, single-center Brazilian cohort.

Affiliation

Hatzlhofer BLD(1)(2), Pereira-Martins DA(3)(4), de Farias Domingos I(3)(5), Arcanjo GDS(3), Weinhäuser I(4), Falcão DA(3), Farias ICC(6), de Freitas Batista JVG(3), Prado LPL(3), Oliveira JMF(3), Batista THC(3), Sobreira MJVC(3), de Santana RM(3), Araújo ABS(3), de Melo MA(3), de Ancântara BV(3), Coelho-Silva JL(3)(7), de Moura Rafael ABL(3), de Lima Silva DM(3), Albuquerque FP(3)(8), Santos MNN(9), Dos Anjos AC(10), Costa FF(8), da Silva Araújo A(10), Lucena-Araújo AR(3), Bezerra MAC(3).
Author information:
(1)Department of Pharmaceutical Sciences, Health Sciences Centre, Federal University of Pernambuco, Av. Prof. Arthur de Sá, s/n, Cidade Universitária, Recife, PE, 50740-521, Brazil. [Email]
(2)Genetics Postgraduate Program, Centre of Biosciences, Federal University of Pernambuco, Recife, Brazil. [Email]
(3)Genetics Postgraduate Program, Centre of Biosciences, Federal University of Pernambuco, Recife, Brazil.
(4)Department of Internal Medicine, Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.
(5)Department of Clinical and Toxicological Analysis, Federal University of Rio Grande do Norte, Natal, Brazil.
(6)Biological Science Institute and College of Medical Sciences, University of Pernambuco, Recife, Brazil.
(7)Department of Medical Images, Hematology and, Clinical Oncology of The University of São Paulo, Ribeirão Preto Medical School, Ribeirão Preto, Brazil.
(8)Hematology and Hemotherapy Centre, State University of Campinas, Campinas, São Paulo, Brazil.
(9)Department of Clinical Pathology, School of Medical Sciences, State University of Campinas, Campinas, São Paulo, Brazil.
(10)Department of Internal Medicine, Hematology and Hemotherapy Foundation of Pernambuco, Recife, Brazil.

Abstract

Alpha thalassemia and beta-globin haplotype are considered classical genetic disease modifiers in sickle cell anemia (SCA) causing clinical heterogeneity. Nevertheless, their functional impact on SCA disease emergence and progression remains elusive. To better understand the role of alpha thalassemia and beta-globin haplotype in SCA, we performed a retrospective study evaluating the clinical manifestations of 614 patients. The univariate analysis showed that the presence of alpha-thalassemia -3.7-kb mutation (αα/-α and -α/-α) decreased the risk of stroke development (p = 0.046), priapism (p = 0.033), and cholelithiasis (p = 0.021). Furthermore, the cumulative incidence of stroke (p = 0.023) and cholelithiasis (p = 0.006) was also significantly lower for patients carrying the alpha thalassemia -3.7-kb mutation. No clinical effects were associated with the beta-globin haplotype analysis, which could be explained by the relatively homogeneous haplotype composition in our cohort. Our results reinforce that alpha thalassemia can provide protective functions against hemolysis-related symptoms in SCA. Although, several genetic modifiers can impact the inflammatory state of SCA patients, the alpha thalassemia mutation remains one of the most recurrent genetic aberration and should therefore always be considered first.