Association of the TSHR Gene Intronic Single Nucleotide Polymorphism rs2268458 With Non-autoimmune Hypothyroidism: A...

Background Nonautoimmune hypothyroidism is underexplored despite its potential metabolic and muscular complications. This study investigated the thyroid-stimulating hormone receptor (TSHR) intronic single nucleotide polymorphism (SNP) rs2268458 to assess its association with non-autoimmune hypothyroidism in an Indian population. Methods A hospital-based cross-sectional study was conducted between May 2023 and July 2024 and included 36 patients with non-autoimmune hypothyroidism, 22 healthy controls, and 13 autoimmune hypothyroid patients (positive controls). Thyroid function (T3, T4, and thyroid-stimulating hormone (TSH)) and anti-thyroid peroxidase (anti-TPO) antibody levels were measured using electrochemiluminescence immunoassay. Genotyping of the TSHR rs2268458 polymorphism was performed using PCR-restriction fragment length polymorphism (PCR-RFLP) and confirmed by Sanger sequencing. Genotype and allele frequencies were analyzed in relation to thyroid biochemical parameters. Results The patients showed significantly higher TSH and lower T3 levels than controls (p < 0.05), along with elevated T4 levels. Anti-TPO antibody levels were substantially lower than those observed in autoimmune hypothyroid patients. The TC genotype was the most frequent among patients (52.78%), whereas healthy controls demonstrated a higher frequency of the CC genotype. Genotype distribution differed between patients and controls, with predominance of the TC genotype among patients. Conclusion The TSHR intronic SNP rs2268458 may be associated with non-autoimmune hypothyroidism, with predominance of the TC genotype among affected individuals. These findings suggest a possible role of TSHR genetic variation in disease susceptibility independent of overt autoimmunity. Further large-scale and functional studies are required to validate these observations.