Identification of the Thyroid-stimulating Hormone Receptor c.2181G>C Variant in Hypothyroid Cases among Mongoloid Population of Northeast India
Trisha Sonowal, Jatin SarmahAbstract
Background:
Genetic alterations in thyroid-stimulating hormone receptor (TSHR) are associated with a spectrum of thyroid disorders which either result hypothyroidism or hyperthyroidism.
Objective:
The present study aimed to screen for mutations or genetic variants in the TSHR gene among individuals with hypothyroidism and hyperthyroidism from the Mongoloid ethnic population of Northeast India, a genetically distinct and underrepresented group.
Methods:
Thyroid function parameters, including thyroid-stimulating hormone, triiodothyronine, tetraiodothyronine, free triiodothyronine, and free thyroxine, were measured using a chemiluminescence immunoassay system. Individuals diagnosed with hypothyroidism were selected for molecular analysis. Genomic DNA was extracted from peripheral blood samples and subjected to polymerase chain reaction amplification targeting exons 7, 9, and 10 of the TSHR gene. Amplified products were analyzed using agarose gel electrophoresis and subsequently sequenced by Sanger sequencing. Sequence alignment and variant identification were performed using BioEdit and Basic Local Alignment Search Tool against the reference sequence (Gene ID: 7253; RefSeq: NC_000014.9).
Results:
Out of 900 individuals, 223 (24.69%) were hypothyroid and 11 (1.22%) were hyperthyroid. A higher prevalence of hypothyroidism was observed with 223 (24.69%) cases than hyperthyroidism with 11 (1.22%) cases. Sanger sequencing identified the TSHR exon 10 variant c.2181G>C (rs1991517) in 18 hypothyroid cases, resulting in an amino acid substitution p.Glu727Asp (E727D).
Conclusion:
The c.2181G>C (p.E727D) variant of the TSHR gene was identified in hypothyroid individuals from the Mongoloid population of Northeast India.