Ancestralidade como fator de risco para hipotireoidismo: estudo da coorte ELSA-BRASIL

Abstract

Introduction– Genomic ancestry refers to the genetic relationship between an individual and their ancestors, from whom they biologically descend. The self-reported ancestry of the Brazilian population is subject to important genomic divergence and there are sensitive markers capable of stratifying the three main Brazilian ancestral roots. The prevalence of hypothyroidism in Brazil is approximately 7.4% and has been highlighted as possibly one of the highest in the world. The ELSA-Brazil-thyroid study showed that women self-reported as white have a higher frequency of hypothyroidism than brown and black women. Objective – To determine genomic ancestry as a risk factor for hypothyroidism. Material and methods – 9372 participants (53.8% women; average age 51 years) from the ELSA-Brazil study cohort were included. Purified DNA was obtained from participants' peripheral blood using the QIAamp DNA Mini-kit1. Samples were genotyped using a panel of 192 ancestry-informative markers. Genomic ancestry analysis was conducted using the ADMIXTURE program. Results – The prevalence of subclinical hypothyroidism (SCH) and clinical hypothyroidism (CH) was found to be 9% and 7.1%, respectively; Female sex increased the risk of CH by 4.43 and 4.68, respectively, in univariate and multivariate logistic regression analyses. Regarding predominant genomic ancestry, genotyping divided individuals into 69.9% with European predominance (EUR), 13% African (AFR), 4.6% native and 12.5% with multiancestry genotype. The EUR subgroup had the highest prevalence of CH (7.9%), demonstrating that EUR ancestry is associated with a higher risk of CH while African genomic ancestry (AFR) and multiancestry played a protective role. On the other hand, the predominant AFR genomic ancestry had the highest percentage of hyperthyroidism (1.7%). Obesity increased the risk of CH and the percentage of hypertension, diabetes mellitus and obesity were significantly higher in the predominant AFR genomic ancestry subgroup. TSH demonstrated a directly proportional relationship with EUR ancestry (p < 0.01) and inversely proportional relationship with AFR (p < 0.01), as well as with free T4 (p < 0.01). Conclusion – Our results demonstrate the important influence of ancestry on thyroid diseases and associated diseases.