Introduction: Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy, with a steadily increasing incidence in the last few decades worldwide. Studies revealed the predisposition to PTC by the heterozygous state of rs2910164 within the precursor of microRNA146a. Interestingly, on the same chromosome, 40Kb separate the pre-miR-146a from the pituitary tumour transforming gene (PTTG1), a proto-oncogene involved in thyroid carcinomas. A genome-wide study revealed an association of the genomic region encompassing pre-miR-146a and PTTG1 gene with systemic lupus erythematosus. In this study, we analyzed, with a casecontrol design, the genetic association between PTC and pre-miR-146a rs2910164 as well as PTTG1 (rs1862391A/C and rs2910201C/T).
Methods: Two hundred and six healthy controls (3078 of age) and 307 PTC patients (3074 of age) were enrolled. The diagnosis of PTC was histological at surgery. Thyroid sonography was performed in controls to exclude nodules. SNP genotyping of pre-miR-146a and PTTG1 was performed by Sanger sequencing and high resolution melting. Linkage disequilibrium (LD) analysis and statistics were performed with Haplowiev 4.2 and GraphPad Prism5 software.
Results and conclusions: Pre-miR-146a rs2910164 allelic frequencies were not statistically different in patients (C=24.3%) and controls (C=28.6%) and the SNP was not in LD with the investigated PTTG1 SNPs. We did not confirm a previously described association of the CG genotype with PTC. However, a significant association between the GG genotype and PTC (GG vs GC+CC odds ratio=1.38, 95% CI 0.82.4) was found. The PTTG1 SNPs (rs1862391A/C and rs2910201C/T), in perfect LD, have the same allelic frequency in patients (A=76.7%) and controls (A=76.2%) and are not associated with PTC. In conclusion, the study showed a new evidence of association between pre-miR-146a rs2910164 and PTC while PTTG1 did not seem to be involved.
27 Apr - 01 May 2013
European Society of Endocrinology