A STUDY ON ASSOCIATION OF TETRANUCLEOTIDE DUPLICATION (-GGCC-) OF TPO GENE WITH HYPOTHYROIDISM

Abstract

Thyroid disorders are one of the most common endocrine disorders in the world, of which hypothyroidism with iodide organification defects (IOD) is prominent. Congenital hypothyroidism (CH) is a severe type of hypothyroidism, mainly attributed to genes like PAX8, DUOX2, SLC5A5, TPO, TG, TSHR and TSHβ etc. These genes are involved in metabolism of thyroid hormones. TPO is a membrane bound glycoprotein with 110 KD and is located on the chromosome number 2p25. It is involved in iodination of tyrosine residues in thyroid gland. Mutations in TPO gene effect IDA (Iron deficiency anemia) and iodide metabolism of thyroid. Over the years, as many as 60 TPO SNPs have been identified, of which a tetranucleotide insertion -GGCC- (rs p.R396fsX472) in exon 8 is one of the most common that causes premature stop codon in exon nine. This is the main cause of inborn errors in the metabolism of thyroid hormones, which leads to TIOD, PIOD or thyroid dyshormogenesis and AITD. This hospital based study was conducted to access the association of rs p.R396fsX472 with hypothyroidism in Hubbali, Karnataka. Blood samples of hypothyroidism patients and matched controls were collected and genotyped using PCR-RFLP technique. rs p.R396fsX472 was observed in 10% of the cases and none in the control group. The findings suggest that anomalies in TPO may be associated with iodine deficiency in case of hypothyroidism in Indian population.