ANALYSIS OF NOVEL THYROID PEROXIDASE GENE VARIANTS FROM THE GNOMAD DATABASE USING IN SILICO BIOINFORMATICS ALGORITHMS AND LITERATURE REVIEW

MARICEL F MOLINA; MAURICIO GOMES PIO; SCHEPS, KAREN G.; ADROVER, EZEQUIELA

Congreso; LXVII Reunión Anual de la Sociedad Argentina de investigación Clínica; 2022

Thyroid peroxidase (TPO) is a thyroid-specific enzyme that plays a key role in thyroid hormones biosynthesis and is the major autoantigen in Hashimoto’s disease, the most common organ-specific autoimmune disease. TPO catalyzes both iodination and coupling of iodotyrosine residues within the thyroglobulin molecule. Variants in TPO gene cause congenital hypothyroidism (CH) by iodide organification defect and are commonly inherited in an autosomal recessive manner. In the present study, we report a detailed analysis and bioinformatic prediction of the TPO variants reported in the Genome Aggregation Database (gnomAD) v2.1.1. 456 variants from unrelated individuals were analized using prediction tools such us PROVEAN, SIFT, PolyPhen-2, Fsplice, among others. The proportion of missense cysteine, nonsense, frameshift, and splice acceptor/donor variants were analyzed in each ethnic group included in the gnomAD v2.1.1 dataset. The results showed a clear predominance of frameshift variants in the East Asian (82%) and European (Finnish) (75%) population, whereas the splice site variants predominate in African/African Americans (99.46%), Other (96%), Latino/Admixed American (94%), South Asian (86%), European (Non-Finnish) (56%) and Ashkenazi Jewish (56%) populations with a significant p value