Comprimento telomérico e sua associação com marcadores socioeconômicos e polimorfismos genéticos determinantes do estado de vitamina D: Estudo Pró-Saúde

Abstract

Telomere length in adult life is a consistent predictor of earlier onset of cardiovascular and metabolic diseases. The knowledge of social and biological determinants of telomere length is critical to evaluate the risk of early biological aging. In this thesis we present two original manuscripts that investigated the association of LTL with socioeconomic and demographic markers (manuscript 1) and serum concentrations of 25(OH)D and single nucleotide polymorphisms (SNPs) related to vitamin D metabolism (manuscript 2). This is a cross-sectional study conducted with part of a cohort of employees from a University in the State of Rio de Janeiro - the Pró-Saúde Study (n = 470; 51 ± 8 years; 52% women). Information on race/skin color, educational attainment, marital status, household income, smoking status, physical activity and medical diagnoses of chronic disease were self-reported during the interview. The LTL of each sample was measured by quantitative Real-Time polymerase chain reaction (qPCR). Serum concentrations of 25(OH)D were evaluated by chemiluminescence immunoassay. The polymorphisms genotyping (rs12785878, rs10741657, rs6013897 and rs2282679) was performed by Real-Time PCR. In the first manuscript, after adjustment for age and potential health-related covariates, lower educational attainment was associated with shorter LTL only in men (β = -0.05; 95% CI -0.09, -0.01). Both women and men showed the expected relationship between older age with shorter LTL (r = -0.19, P < 0.01 and r = -0.18, P <0.01, respectively). However, there was a more pronounced gradient in the inverse relationship between LTL and age in men with lower educational attainment (r = -0.31, P <0.01). In the second manuscript, categories of 25(OH)D serum concentrations were not associated with LTL (P = 0.19). After adjustments, participants with CC genotype (GC gene - rs2282679) had significantly shorter LTL than those with AC and AA genotypes (mean ± SE: 0.50 ± 0.03, 0.58 ± 0.01 and 0.57 ± 0.01, respectively, P < 0.05). Using adjusted multivariate regression models, CC genotype (GC gene - rs2282679) was inversely associated with LTL ( = -0.07; 95% CI -0.13, -0.01). In men, those with AC and CC (GC gene - rs2282679) had higher odds ratio for LTL below the median (0.54), compared to those with AA genotype (OR= 4.78; 95% CI 1.19, 19.17, and OR=4.61; 95% CI 1.18, 17.90, respectively). Our results suggest that educational attainment may be an important socioeconomic marker that can affect LTL, especially among men. In addition, we also suggest that the SNP rs2282679, involved in the synthesis of vitamin D binding protein (DBP), can modulate LTL and SNPs associated with vitamin D metabolism may indicate more accurately the influence of this vitamin on telomere length