Affiliations: [a] Department of Biological Sciences, International Islamic University, Islamabad, Pakistan | [b] Government Medical College Srinagar and Associated Hospitals, Srinagar, India | [c] Department of Pathology, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, India | [d] Research Centre for Modeling and Simulation, National University of Science and Technology, Islamabad, Pakistan
Correspondence:
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Corresponding author: Mosin Saleem Khan, Department of Biochemistry, Government Medical College Srinagar and Associated Hospitals, Srinagar, Kashmir 190010, India. Tel.: +91 941 900 5923; E-mail: [email protected].
Abstract: BACKGROUND: Somatic variations in rearranged during transfection (RET) proto-oncogene acts to influence Thyroid cancer (TC) in a low penetrance manner, but their effects tend to vary between different populations. OBJECTIVE: This case-control study was aimed to evaluate effect of RET G691S, S904S and L769L single nucleotide polymorphisms (SNPs) on the risk for differentiated thyroid carcinoma (DTC). METHODS: A total of 180 patients and 220 controls were genotyped by Polymerase chain reaction – restriction fragment length polymorphism (PCR-RFLP). Di-Deoxy Sanger sequencing was performed on 100 samples with variations and 20 wild samples for each amplified exon. In addition, In Silico tools were used to evaluate structural and functional impact of individual SNPs in disease progression. RESULTS: In RET G691S/L769L/S904S SNPs, frequency of variant genotypes in DTC cases was 61.1%, 54.4% and 76.6% as compared to 45.9%, 43.6% and 89.09% in controls respectively (P⩽ 0.05). In Silico analysis revealed that different protein formed due to G691S substitution decreases the stability of 3D structure of protein. The RET G691S and L769L SNP followed “Dominant” but RET S904S SNP confirmed an “Additive” mode of inheritance. CONCLUSION:RET G691S/L769L/S904S SNPs are significantly associated with DTC with G691S SNP declining the stability of final protein product.
