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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front Med    2014, Vol. 8 Issue (1) : 113-117     DOI: 10.1007/s11684-014-0310-x
RESEARCH ARTICLE |
Are the SNPs of NKX2-1 associated with papillary thyroid carcinoma in the Han population of Northern China?
Lizhe Ai1, Yaqin Yu1, Xiaoli Liu2, Chong Wang1, Jieping Shi1, Hui Sun2, Qiong Yu1()
1. Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun 130021, China; 2. Jilin Provincial Key Laboratory of Surgical Translational Medicine, Department of Thyroid and Parathyroid Surgery, China-Japan Union Hospital, Jilin University, Changchun 130033, China
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Abstract  

Papillary thyroid carcinoma (PTC) is one of the most common tumors of the thyroid gland. The common risk factors of PTC include ionizing radiation, positive family history, and thyroid nodular disease. PTC was identified in Europeans by conducting a genome-wide association study, and a strong association signal with PTC was observed in rs944289 and NKX2-1 (located at the 14q13.3 locus), which was probably the genetic risk factor of PTC. This study aimed to examine the association of this gene with PTC in Chinese. A total of 354 patients with PTC and 360 healthy control subjects from the Han population of Northern China were recruited in the study. These individuals were genotyped to determine rs12589672, rs12894724, rs2076751, and rs944289. The association of rs944289 with PTC was obtained (C vs. T, P=0.027, OR=1.264, 95% CI=1.026-1.557; and C/C-C/T vs. T/T, P=0.034, OR=1.474, 95% CI=1.028-2.112). Conducting a subgroup analysis, we found a marginal difference in the allele frequency distribution of rs944289 (adjusted P=0.062) between the patients with PTC and multi-nodular goiter and the control subjects. We also observed an interaction (P=0.029; OR=2.578, 95% CI=1.104-6.023) between rs944289 and diabetes in patients with PTC. In conclusion, rs944289 was associated with an increased risk of PTC in the Han population of Northern China, but no clear association was observed in either of the tag single nucleotide polymorphisms of NKX2-1.

Keywords NKX2-1      papillary thyroid carcinoma      the Han population of Northern China      association     
Corresponding Authors: Yu Qiong,Email:yuqiong@jlu.edu.cn   
Issue Date: 26 April 2014
URL:  
http://academic.hep.com.cn/fmd/EN/10.1007/s11684-014-0310-x     OR     http://academic.hep.com.cn/fmd/EN/Y2014/V8/I1/113
SNPsPrimer sequence
rs12589672F5′-ACGTTGGATGACTCTGGCCCTCATAGACG-3′
R5′-ACGTTGGATGGGCTTCTGCTTCTCCCTTTC-3′
rs12894724F5′-ACGTTGGATGGAAATAATGGCGAGTGAGAG-3′
R5′-ACGTTGGATGTCCCGAATGGGGTCTAATTG-3′
rs2076751F5′-ACGTTGGATGAGAGAGGCAGACAGACTGAC-3′
R5′-ACGTTGGATGAACAAATGAGCGAGCGAGTC-3′
rs944289F5′-ACGTTGGATGCTTGCAATTTAATTTGGTTG-3′
R5′-ACGTTGGATGAGCCTGTGAATGGACATTAG-3′
Tab.1  Primer sequences of SNPs
Reference allele frequencyVariant allele frequencyH-W equilibrium P valueχ2POR (95% CI)
CaseControlCaseControlCaseControl
rs12589672 (A/Ta)All62763781830.2140.2520.0030.9590.991 (0.716-1.373)
MNG (+)46763751830.7320.2520.8830.347*0.838 (0.580-1.212)*
MNG (-)16063730830.2080.2522.5100.226*1.439 (0.858-2.413)*
rs12894724 (C/Ta)All63364275780.2550.6720.0220.8830.975 (0.697-1.364)
MNG (+)47364245780.9720.6721.5510.213*0.783 (0.532-1.152)*
MNG (-)16064230780.2080.6723.5300.120*1.543 (0.917-2.598)*
rs2076751 (G/Ta)All5855861231340.2200.3900.3710.5430.919 (0.702-1.205)
MNG (+)426586921340.4360.3900.1460.702*0.944 (0.704-1.266)*
MNG (-)159586311340.2690.3900.5340.702*0.853 (0.523-1.391)*
rs944289 (C/Ta)All3624103463100.4620.8744.8600.0271.264 (1.026-1.557)
MNG (+)2634102553100.2400.8744.6260.062*1.282 (0.989-1.662)*
MNG(-)99410913100.6010.8741.4280.232*1.216 (0.882-1.675)*
Tab.2  Association between allelic distributions of SNPs and PTC in a Northern Chinese Han population
ModelGenotypeCaseControlχ2POR (95% CI)
rs12589672OverdominantA/A-T/T2872910.0070.9351.000
A/T67690.985 (0.678-1.431)
rs12894724OverdominantC/C-T/T2912920.1420.7061.000
C/T63680.930 (0.636-1.358)
rs2076751OverdominantG/G-T/T2592462.0120.1561.000
G/T951140.792 (0.573-1.094)
rs944289RecessiveC/C-C/T2662944.4930.0341.000
T/T88661.474 (1.028-2.112)
Tab.3  Association results of the genotypic distributions of SNPs in patients with PTC and control subjects from Northern Chinese Han population
Ionizing radiationFamily historyDiabetes
POR (95% CI)POR (95% CI)POR (95% CI)
rs125896720.7791.102 (0.558-2.178)0.0640.152 (0.021-1.118)0.1622.057 (0.749-5.625)
rs128947240.5621.225 (0.617-2.430)0.0780.166 (0.023-1.224)0.1062.307 (0.837-6.361)
rs20767510.4190.773 (0.414-1.444)0.8831.084 (0.511-2.302)0.6850.799 (0.270-2.366)
rs9442890.4630.845 (0.539-1.325)0.2500.705 (0.389-1.278)0.0292.578 (1.104-6.023)
Tab.4  Interactions between allele frequencies of SNPs and exposed risk factors of patients with PTC from Northern Chinese Han population
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