engleski

Genetic variants in the ST6GAL1 gene are associated with thyroglobulin plasma levels in healthy individuals

Background: Thyroglobulin (Tg) is the largest and most abundant protein in the thyroid gland that serves as a precursor for thyroid hormone synthesis. A twin study showed that there is a strong genetic component to the variability of serum Tg ; however, no genome-wide association study (GWAS) of serum/plasma Tg levels has been reported so far. The aim of this study was to identify genetic variants associated with plasma Tg levels among healthy individuals. Methods: We performed GWAS meta-analysis within two Croatian populations, CROATIA_Split and CROATIA_Korcula. The analyses included 1094 healthy individuals. The selection of healthy individuals was based on detailed thyroid function assessment (including measurements of Tg, TSH, fT3, fT4, TgAb, and TPOAb) and anamnestic data. A total of 7 597 379 variants, imputed using the 1000 Genomes reference panel, were analysed for the association. GWAS was performed under an additive model, controlling for age, gender, and relatedness within each data set. Meta-analysis was conducted using the inverse-variance fixed-effects method. Results: Sixteen polymorphisms located on chromosome 3 within the ST6GAL1 gene reached genome-wide significance. The most significant SNP was rs4012172 (P=1.29x10-10), which explained 3.19% of the variance in Tg levels. ST6GAL1 belongs to the sialyltransferase proteins family which has a fundamental role in the synthesis of specific sialylated structures on various glycoproteins, including thyroglobulin. ST6GAL1 could have a role in the regulation of thyroglobulin level through receptor-mediated signalling transduction, helping to recycle immature Tg from thyrocytes into the follicle lumen, subsequently causing the alteration of Tg release in the circulation. Conclusions: In this first reported GWA meta- analysis of Tg levels, we identified a highly biologically plausible locus that could have a role in the regulation of plasma Tg levels in healthy individuals.

genome-wide association analysis ; thyroglobulin

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