Investigação de biomarcadores do estado nutricional de vitamina D em gestantes e de seus determinantes sociodemográficos, de estilo de vida e genéticos

Abstract

The knowledge of the determinants of vitamin D status in pregnant women is particularly important due to the potential implications of its insufficiency for both maternal and fetal health. In addition to sociodemographic and lifestyle factors, it is possible that single nucleotide polymorphisms (SNPs) determine the genetic predisposition of pregnant women to inadequate vitamin D status. Pregnancy is associated with important changes in vitamin D metabolism. Vitamin D status assessment in pregnant women based exclusively on the serum concentrations of the conventional vitamin D indicator [25(OH)D] has been questioned. In the present thesis, two original manuscripts are presented investigating a broad set of biomarkers of nutritional vitamin D status in Brazilian pregnant women and their demographic and lifestyle determinants (manuscript 1), as well as the association between concentrations of these biomarkers and SNPs the gene encoding vitamin D binding protein (DBP - GC gene) (manuscript 2). This is a cross-sectional study with a convenience sample (n = 123) conducted in women in the third trimester of pregnancy attended at a public maternity of the Municipal health in Rio de Janeiro, Brazil. Information on maternal age, educational attainment, gestational age, pre-gestational BMI, number of previous pregnancies, smoking habit, drinking habits and practicing of physical exercise during pregnancy were self-reported at the time of the interview. The skin pigmentation was evaluated using a portable colorimeter. Serum concentration of total 25(OH)D3 was measured by high-performance liquid chromatography coupled with diode array detector (HPLC-DAD). Serum concentrations of albumin, DBP and PTH were determined. Free and bioavailable fractions of 25(OH)D3 were indirectly estimated based on the protein-ligand binding kinetics. The genotyping of the SNPs rs2282679 (G>T), rs4588 (G>T) e rs7041 (A>C) were performed by Real-Time PCR. In the first manuscript, using multiple linear regression analysis, gestational age was inversely associated with 25(OH)D3 concentrations, whereas pre-pregnancy BMI was directly associated with DBP concentrations (β = 5.84, 95% CI: 0.62, 11.06). Lower concentrations of 25(OH)D3, DBP and free and bioavailable 25(OH)D3 fractions were observed in women who had blood collected during the winter and autumn. In the second manuscript, after adjustments for season, gestational age and pre-pregnancy BMI, women with GG genotype (rs2282679) had lower DBP concentrations compared to those with TT genotype. The genotypes GT and GG (rs2282679) were associated with the highest PTH concentrations (β = 14.53, 95% CI: 3.86, 25.20 and β = 19.66, 95% CI: 0.28, 39, 04), while lower concentrations of PTH were observed in women with GT and TT genotypes at the SNP rs4588 (β = -14.12; 95% CI: -25.47, -2.78 and β = -19.39; 95% CI: -38.88, 0.11, respectively). Our results suggest that the season of the year, gestational age and pre-pregnancy BMI are the main factors determining the predisposition of pregnant women to vitamin D insufficiency and that, apparently, total 25(OH)D3, as well as its free and bioavailable fractions, provide similar information about vitamin D status in Brazilian pregnant women. The results also suggest that although the evaluated SNPs were not associated with 25(OH)D3 (both total and fractions), it appears that they may influence PTH concentrations, considered a marker of vitamin D function.