1 - Laboratório de Genética, Instituto de Saúde Ambiental, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal.
2 - Instituto de Investigação Científica Bento da Rocha Cabral, Lisbon, Portugal.
3 - Serviço de Genética Médica, Hospital de Dona Estefânia, Lisbon, Portugal.
4 - Unidade de Hematologia, Hospital de Dona Estefânia, Lisbon, Portugal.
5 - Departamento de Genética Humana, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisbon, Portugal.
Clin Hemorheol Microcirc. 2016;64(4):957-963. doi: 10.3233/CH-168008. (publicação)
BACKGROUND: Sickle cell anemia (SCA) is an inherited blood disorder. SCA patients present clinical and hematologic variability that cannot be only explained by the single mutation in the beta-globin gene. Others genetic modifiers and environmental effects are important for the clinical phenotype. SCA patients present arginine deficiency that contributes to a lower nitric oxide (NO) bioactivity.
OBJECTIVE: The aim of this work is to determine the association between hematological and biochemical parameters and genetic variants from eNOS gene, in pediatric SCA patients.
METHODS: 26 pediatric SCA patients were genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques in three important eNOS gene polymorphisms - rs2070744, rs1799983 and intron 4 VNTR.
RESULTS: Results from this study show a significant statistical association between some parameters and genetic variants: an increased reticulocyte count and high serum lactate dehydrogenase levels were associated with both the rs2070744_TT and the rs1799983_GG genotypes at eNOS gene and high levels of neutrophils were associated with the eNOS4a allele at intron 4 VNTR.
CONCLUSIONS: Our results reinforce the importance of NO bioactivity in SCA. We presume that NO, and its precursors might be used as therapy to improve the quality of life of SCA patients.
Keywords: Sickle cell anemia; genetic modifiers; nitric oxide