Association of FOXE1 polyalanine repeat region with papillary thyroid cancer

Bullock, Martyn, Duncan, Emma L., O'Neill, Christine, Tacon, Lyndal, Sywak, Mark, Sidhu, Stan, Delbridge, Leigh, Learoyd, Diana, Robinson, Bruce G., Ludgate, Marian and Clifton-Bligh, Roderick J. (2012) Association of FOXE1 polyalanine repeat region with papillary thyroid cancer. Journal of Clinical Endocrinology and Metabolism, 97 9: E1814-E1819. doi:10.1210/jc.2012-1456

Author Bullock, Martyn
Duncan, Emma L.
O'Neill, Christine
Tacon, Lyndal
Sywak, Mark
Sidhu, Stan
Delbridge, Leigh
Learoyd, Diana
Robinson, Bruce G.
Ludgate, Marian
Clifton-Bligh, Roderick J.
Total Author Count Override 11
Title Association of FOXE1 polyalanine repeat region with papillary thyroid cancer
Journal name Journal of Clinical Endocrinology and Metabolism   Check publisher's open access policy
ISSN 0021-972X
Publication date 2012-09
Sub-type Article (original research)
DOI 10.1210/jc.2012-1456
Volume 97
Issue 9
Start page E1814
End page E1819
Total pages 6
Place of publication Chevy Chase, MD, United States
Publisher The Endocrine Society
Collection year 2013
Language eng
Formatted abstract
Context: Polyalanine tract variations in transcription factors have been identified for a wide spectrum of developmental disorders. The thyroid transcription factor forkhead factor E1 (FOXE1) contains a polymorphic polyalanine tract with 12–22 alanines. Single-nucleotide polymorphisms (SNP) close to this locus are associated with papillary thyroid cancer (PTC), and a strong linkage disequilibrium block extends across this region.
Objective: The objective of the study was to assess whether the FOXE1 polyalanine repeat region was associated with PTC and to assess the effect of polyalanine repeat region variants on protein expression, DNA binding, and transcriptional function on FOXE1-responsive promoters.
Design: This was a case-control study.
Setting: The study was conducted at a tertiary referral hospital.
Patients and Methods: The FOXE1 polyalanine repeat region and tag SNP were genotyped in 70 PTC, with a replication in a further 92 PTC, and compared with genotypes in 5767 healthy controls (including 5667 samples from the Wellcome Trust Case Control Consortium). In vitro studies were performed to examine the protein expression, DNA binding, and transcriptional function for FOXE1 variants of different polyalanine tract lengths.
Results: All the genotyped SNP were in tight linkage disequilibrium, including the FOXE1 polyalanine repeat region. We confirmed the strong association of rs1867277 with PTC (overall P = 1 × 10−7, odds ratio 1.84, confidence interval 1.31–2.57). rs1867277 was in tight linkage disequilibrium with the FOXE1 polyalanine repeat region (r2 = 0.95). FOXE116Ala was associated with PTC with an odds ratio of 2.23 (confidence interval 1.42–3.50; P = 0.0005). Functional studies in vitro showed that FOXE116Ala was transcriptionally impaired compared with FOXE114Ala, which was not due to differences in protein expression or DNA binding.
Conclusions: We have confirmed the previous association of FOXE1 with PTC. Our data suggest that the coding polyalanine expansion in FOXE1 may be responsible for the observed association between FOXE1 and PTC.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2013 Collection
UQ Diamantina Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 23 times in Thomson Reuters Web of Science Article | Citations
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Created: Mon, 05 Nov 2012, 10:47:43 EST by Roheen Gill on behalf of UQ Diamantina Institute