Avaliação de oito polimorfismos em genes candidatos relacionados à função tireoidiana no idoso

Abstract

Introduction: Cross-sectional and longitudinal population studies point to higher TSH levels with aging. In addition, in older age groups, there is a higher prevalence of frailty, comorbidities and polypharmacy, which requires caution in interpretation of thyroid tests. Serum thyroid parameters show wide interindividual and narrow intraindividual variability, suggesting genetic factors as the main determinant for regulation of thyroid function. Several genetic loci were associated with thyroid function in large studies on association between genotype and phenotype in adult population. However, such findings were not analyzed in the elderly population. Objective: To analyze relationship between 8 polymorphisms of genes associated with thyroid function and serum levels of TSH, free T4 and free T3. Material and Methods: A cross-sectional study with elderly women conducted from 2018 to 2019. Males and patients with subclinical or overt thyroid disease were excluded. Sociodemographic and anthropometric data were collected. Tests were performed on thyroid function and for DNA extraction, which were followed by genotyping of 8 single-nucleotide polymorphisms selected for the study. Statistics: The Mann Whitney U Test was used on all analyses with quantitative variables. Data were presented as median and interquartile range (IQR). In relation to categorical variables, chi-square test was used to compare two proportions-square and Fisher's Exact test was used to assess the association between two qualitative variables. The Hardy-Weinberg-Equilibrium (HWE) was calculated using chi-square test. The statistical software STATA version 10 was used to perform descriptive analyzes and statistical tests. Significance level adopted was 0.05. Association between SNPs and thyroid genetic testing was used as a dominant genetic model. Results: 64 female individuals were included. Median age was 70 years (65-73), 100% female. Median BMI was 26.3kg/m2 (24-30.6). TSH, T4l and T3l medians were, respectively, 2.17 mU / L (1.58-2.97), 1.12 ng / dL (1.04-1.20) and 2.78 pg / ml (2.64-2.98). More than half of individuals had systemic arterial hypertension (62.26%), a quarter (24.53%) had diabetes mellitus and less than half (39.62%) had dyslipidemia. There was a statistically significant difference in TSH levels between wild-type (C) and polymorphic (T) alleles in SNP rs12885300 of DIO2 gene, p = 0.03. In this polymorphism, C/C genotype (present in 69,44% of individuals) showed TSH and T4l medians of 1.89mU/L (2.42), 2.85pg/dL (2.69-2.98) and 1.15ng/mL (1.11-1.21), respectively; set of C/T and T/T genotypes (present in 30.56% of individuals) showed medians of 2.82mU/L (2-4.2), 2.83pg/3.17) and 1.16 ng/mL, respectively. There was also a statistically significant difference in T4l levels between wild-type (T) and polymorphic (C) alleles in SNP rs225014 of DIO2 gene, p = 0.02. In this polymorphism, T/T genotype (present in 29,27% of individuals) showed TSH, T3l and T4l medians of 2,19mU/L (1,78-3,42), 2,99pg/dL (2,75-3,24) e 1,20ng/mL (1,16-1,29), respectively; set of C/T and T/T genotypes (present in 70,73% of individuals) showed medians of 2,2mU/L (1,53-2,8), 2,73pg/dL (2,65-2,92) e 1,12 ng/mL (1,06-1,18), respectively. For other polymorphisms, there were no associations with statistical significance. Conclusion: DIO2 gene rs1285300 polymorphism in homozygosity or heterozygosity was associated with higher TSH levels and DIO2 gene polymorphism in homozygosity or heterozygosity was associated with higher T4l levels. These data, unprecedentedly tested in a Brazilian geriatric population, point to the need to consider genetic aspects in interpretation of thyroid function in the elderly. A better understanding of the important influence of genes to thyroid function may contribute to the development of better treatment strategies for hypothyroidism in elderly patients.