Abstract
TSHR GENE POLYMORPHISM AND ITS ASSOCIATION WITH HYPOTHYROIDISM IN KASHMIRI POPULATION

Gousia Qayoom Mir, Bashir Ahmad Ganai*, Shagufta Sheikh, Shariq Rashid Masoodi, Hilal Ahmad Wani, Akbar Masood

ABSTRACT

Thyroid stimulating hormone receptor gene (THSR) is critical for the normal functioning of the thyroid gland. A mutation in this gene is associated with several disorders of thyroid hormonogenesis including hypothyroidism. In this study, we investigated the role of TSHR codon D727E genetic variants in hypothyroidism. A sample of 445 participants (220 cases and 225 healthy subjects), aged 16-70 years, were randomly selected from among the Kashmiri population. Information on thyroid disease and other lifestyle and environmental exposure were gathered by questionnaire and the patient's endocrinologist or general practitioner verified the diagnosis. The polymorphism of codon D727E of the TSHR gene was identified by polymerase chain reaction-based restriction analysis and direct sequencing. Statistical analysis revealed a single nucleotide polymorphism that is a C-to-G substitution at codon 727 of the TSHR gene (GAC TO GAG). The result showed a 3 fold increased risk among subjects homozygous for G variants as compared to healthy subjects (OR = 3.01; 95% CI = 2.01-4.53; P = < 0.0001). Our study also showed a positive association of the TSHR polymorphism with certain environmental exposures, lifestyle changes, smoking habits and in subjects with high basal metabolic Index (BMI), all of which suggests a possible role of these polymorphisms in the etiology of hypothyroidism in Kashmir.

Keywords: Thyroid stimulating hormone receptor gene, Thyroid peroxidase gene, auto-immune thyroid disorder, Basal Metabolic Index, Goitrogens.


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