Indicadores nutricionais e biomarcadores bioquímicos e moleculares em indivíduos com doença falciforme

Abstract

Studies are still controversial regarding differences between individuals with sickle cell anemia (SCA) and SC disease (HbSC), mainly in relation to the association of nutritional status with severity markers. Phase angle (PhA), a measure of cell membrane integrity, correlates with prognosis in different clinical situations; however, there is still limited information about its correlation with prognostics in sickle cell disease (SCD). Dyslipidemia in SCD is variable and there are few studies indicating a relationship with the severity and genetic variants involved in lipid homeostasis. The aims of this study was to evaluate clinical, nutritional, laboratory and molecular biomarkers in individuals with SCD (SCA and HbSC), the potential of PhA as a predictor of SC severity, the influence of CETP gene variants and haplotypes, as well as associations between the variables and the differences between the two genotypes of SCD. The study has been conducted with children and adolescents with SCD (SCA and HbSC) followed in the blood center of Governador Valadares of the Hemominas Foundation. Demographic, socioeconomic, clinical, anthropometric, laboratory (vitamins A and D, lipid profile and severity markers) and electrical bioimpedance data were collected. Of the 138 participants, 75 had SCA (54.3%) and 63 HbSC (45.7%), with a mean age of 11.63 years. Sixty-four patients with SCA participated in the analyzes involving PhA and the same number in the group without sickle cell disease (WSCD), with an average age of 12.27 and 11.47 years, respectively. The αthalassemia (α-thal) and the polymorphisms in the CETP gene (rs247616, rs183130 and rs3764261) were genotyped. PhA values were defined and compared between WSCD and SCA groups and the relationship of this measure with severity markers in SCA was investigated. Group SCA exhibited higher nutritional deficit, more severe hypocholesterolemia and anemia, as well as greater severity indicated by hemolytic and inflammatory markers compared to group HbSC. In SCA, body mass index, vitamin A, high-density lipoprotein (HDL-C) and apolipoprotein A1 (apoA1) showed an inverse correlation with total leukocytes, lactate dehydrogenase (LDH) and/or total bilirubin (TB). Hemoglobin (Hb) was positively associated with vitamin A and negatively associated with triglycerides (TG). In SCD, individuals with αthal exhibited lower values for the mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH). The PhA value was lower in the SCA individuals and showed association with markers of disease severity. Subjects with SCA using Hydroxyurea had higher levels of HDL-C, however, there was no association between these variables. The absence of the SNP TTA haplotype (rs247616, rs183130 and rs3764261) of the CETP gene tripled the risk of having low HDL-C levels in patients with SCD. In addition, the low levels of Hb also led to risk of low values of this lipoprotein in these patients when analyzing only the SCA group. The study concluded that the SCA group had worse condition compared to the HbSC group when considering nutritional profile and disease severity. Nutritional status was associated with severity markers, especially in SCA. The PhA proved to be a promising variable in predicting the severity of SCA. Variants of the CETP gene together with the intrinsic factors of the hemolytic anemia itself could explain part of the variation observed in dyslipidemia in patients with SCD