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Association of KLOTHO polymorphisms with clinical complications of sickle cell anemia

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Abstract

The clinical and phenotypic heterogeneity of patients with sickle cell anemia (SCA) is influenced by environmental and genetic factors. Several genetic modifiers, such as the KLOTHO (KL) gene, have been associated with SCA clinical outcomes. The KL gene and its encoded proteins are implicated in important biological pathways, which affect the disease’s pathophysiology, such as expression of adhesion molecules VCAM-1 and ICAM-1, oxidative stress, and nitric oxide biology. Here, we evaluated the clinical relevance of two polymorphisms found on the KL gene (rs685417 and rs211239) in 588 unrelated patients with SCA. Genotyping analyses were performed using the TaqMan system. The KL rs211239 was associated with increased number of vaso-occlusive crisis (VOCs) per year (P = 0.001), while KL rs685417 was associated with increased frequency of stroke (P = 0.034), priapism (P = 0.011), number of complications (P = 0.019), and with a lower incidence of priapism (P = 0.036). Additionally, the associations with VOCs, stroke, and priapism remained consistent in multivariate analyses (P < 0.05). Our data highlight the clinical importance of KL in SCA.

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Acknowledgements

The authors thank to the sickle cell anemia patients and their families who made this research possible.

Funding

This investigation was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Grant #483714/2013-5).

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Authors and Affiliations

  1. Genetics Postgraduate Program, Federal University of Pernambuco, Recife, Brazil

    Jéssica V. G. F. Batista, Diego A. Pereira-Martins, Diego A. Falcão, Igor F. Domingos, Gabriela S. Arcanjo, Betânia L. Hatzlhofer, Thais H. C. Batista, Antonio R. Lucena-Araujo & Marcos A. Bezerra

  2. Department of Internal Medicine, Medical School of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil

    Diego A. Pereira-Martins & Isabel Weinhäuser

  3. Department of Clinical and Toxicological Analyses, Federal University of Rio Grande do Norte, Natal, Brazil

    Igor F. Domingos

  4. Department of Pharmaceutical Sciences, Health Sciences Center, Federal University of Pernambuco, Recife, Brazil

    Betânia L. Hatzlhofer

  5. Laboratory of Immunomodulation and Novel Therapeutic Approaches (LINAT), Research Center for Therapeutic Innovation Suely Galdino (NUPIT-SG), Federal University of Pernambuco, Recife, Brazil

    Pablo R. G. Cardoso & Maira G. R. Pitta

  6. Department of Internal Medicine, Hematology and Hemotherapy Foundation of Pernambuco, Recife, Brazil

    Ana C. dos Anjos, Manuela F. Hazin & Aderson S. Araujo

  7. Hematology and Hemotherapy Center, State University of Campinas, Campinas, Brazil

    Fernando F. Costa

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  1. Jéssica V. G. F. Batista
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Contributions

J.V.G.F.B. conceived and designed the study, performed experiments, analyzed and interpreted data, performed the statistical analyses, and drafted the article. D.A.P.M., D.A.F., I.F.D. B.L.H., G.S.A., I.W., T.H.C.B., and P.R.G.C. collected data and reviewed the paper. A.C.A., A.S.A., F.C.F, and M.F.H. recruited patients, updated clinical data, and reviewed the manuscript. M.G.R.P, A.R.L.A., and M.A.B. gave final approval of the submitted version.

Corresponding author

Correspondence to Marcos A. Bezerra.

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Ethics approval and informed consent

The local research ethics board approved this study (CAAE: 58863316.6.3001.5195), and, in accordance with the Declaration of Helsinki, informed consent was obtained from all participants before study commencement. For those under the age of 18 years, informed consent was obtained from their parents or legal guardian.

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The authors declare no competing interests.

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Batista, J.V.G.F., Pereira-Martins, D.A., Falcão, D.A. et al. Association of KLOTHO polymorphisms with clinical complications of sickle cell anemia. Ann Hematol 100, 1921–1927 (2021). https://doi.org/10.1007/s00277-021-04532-w

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