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Genotype Analyses in the Japanese and Belarusian Populations Reveal Independent Effects of rs965513 and rs1867277 but Do Not Support the Role of FOXE1 Polyalanine Tract Length in Conferring Risk for Papillary Thyroid Carcinoma


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Title: Genotype Analyses in the Japanese and Belarusian Populations Reveal Independent Effects of rs965513 and rs1867277 but Do Not Support the Role of FOXE1 Polyalanine Tract Length in Conferring Risk for Papillary Thyroid Carcinoma
Authors: Nikitski, Alyaksandr V. / Rogounovitch, Tatiana I. / Bychkov, Andrey / Takahashi, Meiko / Yoshiura, Koh-ichiro / Mitsutake, Norisato / Kawaguchi, Takahisa / Matsuse, Michiko / Drozd, Valentina M. / Demidchik, Yuri / Nishihara, Eijun / Hirokawa, Mitsuyoshi / Miyauchi, Akira / Rubanovich, Alexander V. / Matsuda, Fumihiko / Yamashita, Shunichi / Saenko, Vladimir A.
Issue Date: 1-Feb-2017
Publisher: Mary Ann Liebert Inc.
Citation: Thyroid, 27(2), pp.224-235; 2017
Abstract: Background: Several functional single-nucleotide polymorphisms (SNPs) at the FOXE1 locus on chromosome 9q22.33 have been associated with the risk for papillary thyroid carcinoma (PTC). This study set out to elucidate whether their effects are independent, using genotyping results in populations of Asian and European descent. Methods: SNPs rs965513 and rs1867277 and a polymorphic region determining the length of the FOXE1 polyalanine (poly-Ala) tract were genotyped in 501 patients with PTC and 748 healthy individuals from Japan, and in 660 patients and 820 population controls from Belarus. Functional analysis of transactivation activities of FOXE1 isoforms with varying number of alanine repeats was performed by a Dual-Luciferase® Assay. Results: All three polymorphisms were significantly associated with PTC in both populations on univariate analysis. However, conditional analysis revealed independent effects of rs965513 and rs1867277 SNPs but not of the FOXE1 poly-Ala polymorphism. The independent effect of the lead rs965513 SNP was observed in both populations, while that of rs1867277 was only identified in the Japanese population, in which linkage disequilibrium between the three polymorphisms is markedly weaker. Despite the strong decrease in transcriptional activity with increasing FOXE1 poly-Ala tract length, no difference in transactivation potential of the FOXE1 poly-Ala isoforms could be seen after adjustment for the minimal promoter activity in the reporter vectors. Plasmids encoding FOXE1 isoforms of increasing poly-Ala tract length were also found to produce less FOXE1 protein after cell transfection. Conclusions: The functional variants rs965513 and rs1867277 independently contribute to genetic predisposition to PTC, while a contributing role of the FOXE1 poly-Ala polymorphism could not be confirmed.
Keywords: case-control association study / FOXE1 polymorphism / functional analysis of transactivation potential / genotype / papillary thyroid carcinoma
URI: http://hdl.handle.net/10069/37435
ISSN: 10507256
DOI: 10.1089/thy.2015.0541
Rights: ©2017 Mary Ann Liebert, Inc. / Final publication is available from Mary Ann Liebert, Inc., publishers http://dx.doi.org/10.1089/thy.2015.0541
Type: Journal Article
Text Version: author
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/37435

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