title: The potential role of the sodium iodide symporter gene polymorphism in the development of differentiated thyroid cancer.
abstract: The sodium iodide symporter (NIS) (solute carrier family 5; SLC5A), mediates the active transport of iodine anion (I(-)) into thyroid follicular cells to facilitate thyroid hormone biosynthesis. Considering its fundamental role in thyroid function, our objective in this study is to explore its potential involvement in the pathogenesis of differentiated thyroid cancer (DTC). Following a preliminary sequencing of the gene in a representative sample of the general population, five variants, (1) rs45602038, (2) rs4808708, (3) rs4808709, (4) rs7250346 and (5) rs12327843, were selected for a larger population-based association study consisting of 507 cases and 597 controls, of which only the rs45602038_TT [Odds ratio (95% confidence interval)=1.90 (1.26-2.88); p=0.002] was associated with disease following adjustment for other confounders using the multivariate analysis. Furthermore, a 5-mer haplotype CGAGT constructed from the five studied SNPs conferred a significant risk (χ(2)=10.98; p=0.0009) for DTC. This association trickled down through shorter derivatives, with the 4-mer haplotype CGAG (χ(2)=13.25; p=0.0003) displaying the most significant association and the 3-mer GAG (χ(2)=11.80; p=0.0006) being equally strongly linked to the disease. Comparison of the flanking derivatives of the primary 5-mer haplotype also indicated that the 3-mer CGA (χ(2)=4.04; p=0.045) constructed from SNP block 1-3 was a lot weaker than that of the AGT (χ(2)=6.73; p=0.0095) constructed from the blocks 3-5 from the other end of the gene. Put together, these data implicate the three nucleotide changes at the rs4808708, rs4808709 and rs7250346 loci (blocks 2-4) as the core for this relationship.
authors.affiliation: Clinical Pharmacy Department, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211, Saudi Arabia; School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton BN2 4GJ, UK. Electronic address: mahalrasheed@ksu.edu.sa.
authors.forename: Maha M
authors.initials: MM
authors.lastname: Al-Rasheed
authors.affiliation: King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211, Saudi Arabia. Electronic address: aliz@kfshrc.edu.sa.
authors.forename: Ali S
authors.initials: AS
authors.lastname: Alzahrani
authors.affiliation: School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton BN2 4GJ, UK. Electronic address: A.Macadam@bton.ac.uk.
authors.forename: Angela
authors.initials: A
authors.lastname: Macadam
authors.affiliation: School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton BN2 4GJ, UK. Electronic address: A.D.J.Overall@brighton.ac.uk.
authors.forename: Andrew
authors.initials: A
authors.lastname: Overall
authors.affiliation: School of Pharmacy and Biomolecular Sciences, University of Brighton, Brighton BN2 4GJ, UK. Electronic address: P.R.Gard@bton.ac.uk.
authors.forename: Paul
authors.initials: P
authors.lastname: Gard
authors.affiliation: King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh 11211, Saudi Arabia. Electronic address: dzimiri@kfshrc.edu.sa.
authors.forename: Nduna
authors.initials: N
authors.lastname: Dzimiri
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies / Q000379:methods; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012529:Saudi Arabia; D017422:Sequence Analysis, DNA; D027981:Symporters / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology*; D000099209:Sodium-Iodide Symporters
chemical_list: D027981:Symporters; D000099209:Sodium-Iodide Symporters
keywords: Association study; Differentiated thyroid cancer; Gene polymorphism; Haplotypes; Sodium iodide symporter gene