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

MAURICIO GOMES PIO; MIGUEL M. ABELLEYRO; KAREN G. SCHEPS; HÉCTOR M. TARGOVNIK; MARICEL F. MOLINA; EZEQUIELA ADROVER; CARINA M. RIVOLTA

Mar del Plata

Congreso; Reunión Anual de la Sociedad Argentina de Investigación Clínica.; 2022

Sociedad Argentina de Investigación Clínica.

Thyroidperoxidase (TPO) is a thyroid-specific enzyme that plays a key role in thyroid hormones biosynthesisand is the majorautoantigen in Hashimoto?s disease, the most common organ-specific autoimmunedisease. TPO catalyzesboth iodination and coupling of iodotyrosine residues within the thyroglobulinmolecule. Variants in TPO gene cause congenital hypothyroidism (CH) by iodideorganification defect and are commonly inherited in an autosomal recessivemanner. In the present study, we report a detailed analysis and bioinformaticprediction of the TPO variants reported in the Genome Aggregation Database(gnomAD) v2.1.1. 456 variants from unrelated individualswere analized using prediction tools such as PROVEAN, SIFT, PolyPhen-2,Fsplice, among others. The proportion of missense cysteine, nonsense,frameshift, and splice acceptor/donor variants were analyzed in each ethnicgroup included in the gnomAD v2.1.1 dataset. The results showed a clearpredominance of frameshift variants in the East Asian (82%) and European(Finnish) (75%) population, whereas the splice site variants predominate inAfrican/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