An investigation into the polymorphisms of TSH R and TPO genes in patients with Thyroid disorder in Kashmir

Abstract

Interactions between individual genetic and environmental factors determine the onset of thyroid disorders. The thyroid-stimulating hormone receptor (TSHR) gene is a convincing candidate gene, wherein the germline mutation has been reported to be associated with certain thyroid diseases. Thyroid peroxidase (TPO) is the key enzyme in the synthesis of thyroid hormones and its (TPO) mutation is one of the most common causes of thyroid dyshormonogenesis, characterized by iodide organification defects. The role of the TSHR and TPO genetic variants in thyroid disorders has not been well studied. This study investigated the possible relationship between the polymorphisms of TSHR gene codon D727E and codon T2229C of the TPO gene and thyroid disorders among the ethnic population of Kashmir. In this case-control study, 500 cases and 500 controls (a total of 446 males and 554 females), aged 16-70 years, were randomly selected from among the Kashmiri population. TSHR gene codon D727E and TPO gene codon T2229C SNPs were detected by PCR and RFLP using N1AIII and Eco57I as the restriction enzymes. Genotyping results were validated by sequencing 10 % of the samples. newlineand#967;2 and Fisher exact tests were used to test the allelic and genotypic associations of each SNP and to assess the association of various genotypes with different thyroid disorder types (hypothyroidism, hyperthyroidism, and goiter), gene-gene and gene-environment interactions. Hardy-Weinberg equilibrium of each SNP in the case and control individuals were also examined using a and#967;2 test. We analyzed non-parametric variables by Mann-Whitney U test. All tests were done using GraphPad InStat software (GraphPad InStat software, San Diego, CA). newlineStatistical analysis revealed that TSHR gene codon D727E variant genotypes (sum of C/G and G/G genotypes) was significantly associated with an increased risk of hypothyroidism (OR = 3.01; 95% CI = 2.011-4.53; P = lt 0.0001). However, no positive association of TSHR gene codon D727E polymorphism was observed for hyperthyroidism.......