The potential role of the sodium iodide symporter gene polymorphism in the development of differentiated thyroid cancer

Maha M. Al-Rasheed, Ali S. Alzahrani, Angela Macadam, Andrew Overall, Paul Gard, Nduna Dzimiri

Research output: Contribution to journalArticleResearchpeer-review

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 (chi(2)=10.98; p=0.0009) for DTC. This association trickled down through shorter derivatives, with the 4-mer haplotype CGAG (chi(2)=13.25; p=0.0003) displaying the most significant association and the 3-mer GAG (chi(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 (chi(2)=4.04; p=0.045) constructed from SNP block 1-3 was a lot weaker than that of the AGT (chi(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.
Original languageEnglish
Pages (from-to)163-168
Number of pages6
JournalGene
Volume572
Issue number2
DOIs
Publication statusPublished - 6 Jul 2015

Fingerprint

Thyroid Neoplasms
Haplotypes
Single Nucleotide Polymorphism
Genes
Active Biological Transport
Thyroid Hormones
Iodine
Population
Anions
Thyroid Gland
Multivariate Analysis
Nucleotides
Odds Ratio
Confidence Intervals
sodium-iodide symporter

Keywords

  • Differentiated thyroid cancer
  • Gene polymorphism
  • Sodium iodide symporter gene
  • Haplotypes
  • Association study

Cite this

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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 (chi(2)=10.98; p=0.0009) for DTC. This association trickled down through shorter derivatives, with the 4-mer haplotype CGAG (chi(2)=13.25; p=0.0003) displaying the most significant association and the 3-mer GAG (chi(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 (chi(2)=4.04; p=0.045) constructed from SNP block 1-3 was a lot weaker than that of the AGT (chi(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.",
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The potential role of the sodium iodide symporter gene polymorphism in the development of differentiated thyroid cancer. / Al-Rasheed, Maha M.; Alzahrani, Ali S.; Macadam, Angela; Overall, Andrew; Gard, Paul; Dzimiri, Nduna.

In: Gene, Vol. 572, No. 2, 06.07.2015, p. 163-168.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - The potential role of the sodium iodide symporter gene polymorphism in the development of differentiated thyroid cancer

AU - Al-Rasheed, Maha M.

AU - Alzahrani, Ali S.

AU - Macadam, Angela

AU - Overall, Andrew

AU - Gard, Paul

AU - Dzimiri, Nduna

PY - 2015/7/6

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N2 - 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 (chi(2)=10.98; p=0.0009) for DTC. This association trickled down through shorter derivatives, with the 4-mer haplotype CGAG (chi(2)=13.25; p=0.0003) displaying the most significant association and the 3-mer GAG (chi(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 (chi(2)=4.04; p=0.045) constructed from SNP block 1-3 was a lot weaker than that of the AGT (chi(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.

AB - 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 (chi(2)=10.98; p=0.0009) for DTC. This association trickled down through shorter derivatives, with the 4-mer haplotype CGAG (chi(2)=13.25; p=0.0003) displaying the most significant association and the 3-mer GAG (chi(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 (chi(2)=4.04; p=0.045) constructed from SNP block 1-3 was a lot weaker than that of the AGT (chi(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.

KW - Differentiated thyroid cancer

KW - Gene polymorphism

KW - Sodium iodide symporter gene

KW - Haplotypes

KW - Association study

U2 - 10.1016/j.gene.2015.07.009

DO - 10.1016/j.gene.2015.07.009

M3 - Article

VL - 572

SP - 163

EP - 168

JO - Gene

JF - Gene

SN - 0378-1119

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ER -