Prevalência da insuficiência/deficiência de vitamina D em Pacientes portadores de fibrose cística: associação com o Perfil inflamatório e polimorfismo foki do gene VDR

Cystic fibrosis is an autosomal recessive disease caused by mutations in the CFTR gene. In Brazil, it has an approximate incidence of 1/7000, subject to regional variations. About 90% of patients have pancreatic insufficiency, resulting in malabsorption and risk of deficiency of fat-soluble vitamins, including vitamin D. Vitamin D has recently been linked to several disease states, such as hypertension, diabetes mellitus, cardiovascular disease, Cancer and chronic obstructive pulmonary disease. Vitamin D has immunomodulatory effects on inflammation. Studies have indicated the existence of several polymorphisms in the VDR gene. These polymorphisms have been studied as possible factors involved in predisposition to diseases as well as in the modulation of vitamin D activity. These new insights into the biological functions of vitamin D have led to interest in the clinical consequences of their deficiency. Based on these facts, the study aimed to identify the prevalence of 25- hydroxyvitamin D deficiency / deficiency in individuals with cystic fibrosis and to analyze its association with the inflammatory profile and FokI polymorphism of the VDR gene. This was a cross-sectional study, conducted with patients who were followed at the Pediatric Outpatient Clinic of the University Hospital Lauro Wanderley - UFPB, involving 18 patients, of both sexes. Socio-demographic information, factors associated with sun exposure and clothing were collected through a questionnaire. Weight, height and arm circumference were measured and a food consumption frequency questionnaire was applied. Blood was collected for analysis of biochemical parameters (25-hydroxyvitamin D, parathyroid hormone, serum calcium, alanine transaminase, aspartate transaminase, urea, creatinine, uric acid, fasting glycemia and blood count), inflammatory markers (C-reactive protein, α-1 glycoprotein Acid) and to verify the presence of FokI polymorphism of the vitamin D receptor VDR gene, analyzed by RFLP. Statistical analysis was performed using Student's independent t-tests (or their non-parametric correspondent, the Mann-Whitney test), Spearman's Chi-square test and Pearson's correlation, adopting a significance of p <0.05. The majority of the participants were male (55.6%). Of the total sample, 33.33% (n = 6) had vitamin D insufficiency / deficiency (19.60 ± 6.180 ng / ml) and 27.8% (n = 5) anemia and low weight for age. Regarding genotypes, 5.6% (n = 1) had FF genotype, 72.3% (n = 13) had Ff genotype and 22.2% (n = 4) presented ff genotype. There was an association between serum levels of 25- hydroxyvitamin D and hemoglobin (p = 0.008), hematocrit (p = 0.019) and leukocytes (p = 0.0114). There was no association between the values of 25-hydroxyvitamin D and the genotypes (FF, Ff and ff) (p = 0.23). In addition, there was an association between FokI polymorphism and total leukocyte count (p = 0.01). There was no association of hemoglobin with nutritional status (p = 0.61). There was also no association between vitamin D and inflammatory profile. When analyzing the frequency of consumption of source foods of vitamin D, it was observed that all the individuals consume whole milk daily. The present study found an association between the serum values of 25-hydroxyvitamin D and those of hemoglobin, hematocrit and leukocytes in the individuals analyzed. In addition, the association of the FokI polymorphism with the total leukocyte count was found.NenhumaA fibrose cística é uma doença autossômica recessiva, causada por mutações no gene CFTR. No Brasil, tem incidência aproximada de 1/7000, sujeita a variações regionais. Cerca de 90% dos pacientes apresentam insuficiência pancreática, resultando em má absorção e risco de deficiência de vitaminas lipossolúveis, incluindo a vitamina D. Recentemente, a vitamina D tem sido associada a vários estados de doença, como hipertensão, diabetes mellitus, doenças cardiovasculares, câncer e doença pulmonar obstrutiva crônica. A vitamina D tem efeitos imunomoduladores na inflamação. Estudos têm indicado a existência de vários polimorfismos no gene do VDR. Estes polimorfismos foram estudados como possíveis fatores envolvidos na predisposição a doenças, bem como na modulação da atividade da vitamina D. Estes novos insights sobre as funções biológicas da vitamina D levaram ao interesse pelas consequências clínicas da sua deficiência. Baseado nestes fatos, o estudo teve como objetivo identificar a prevalência da insuficiência/deficiência de 25-hidroxivitamina D em indivíduos portadores de fibrose cística e analisar sua associação com o perfil inflamatório e o polimorfismo FokI do gene VDR. Tratou-se de um estudo transversal, conduzido com pacientes acompanhados no ambulatório de Pediatria do Hospital Universitário Lauro Wanderley – UFPB, envolvendo 18 pacientes, de ambos os sexos. Foram coletadas, através de um questionário, informações sócio-demográficas, fatores associados à exposição ao sol e vestimentas. Foram medidos o peso, altura e circunferência do braço e aplicado um questionário de frequência de consumo alimentar. Sangue foi coletado para análise de parâmetros bioquímicos (25-hidroxivitamina D, paratormônio, cálcio sérico, alanina transaminase, aspartato transaminase, uréia, creatinina, ácido úrico, glicemia de jejum e hemograma), marcadores inflamatórios (Proteína C Reativa, α-1 glicoproteína ácida) e para verificar a presença do polimorfismo FokI do gene VDR receptor da vitamina D, analisado por RFLP. Análise estatística foi realizada através dos testes t de Student independente (ou seu correspondente não-paramétrico, o teste de Mann- Whitney), Teste do Qui-quadrado de Spearman e Correlação de Pearson, adotando-se significância de p