Association between single nucleotide variants of vascular endothelial growth factor A and the risk of thyroid carcinoma and nodular goiter in a Han Chinese population

Abstract

// Rui Liu 1, * , Lifeng Ning 1, 2, * , Xiaoli Liu 3 , Huiping Zhang 4 , Yaqin Yu 1 , Shangchao Zhang 1 , Wenwang Rao 1 , Jieping Shi 1 , Hui Sun 3 , Qiong Yu 1 1 Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun 130021, China 2 National Research Institute for Family Planning, Beijing 100081, China 3 Jilin Provincial Key Laboratory of Surgical Translational Medicine, China-Japan Union Hospital, Jilin University, Changchun 130033, China 4 Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, USA * These authors have contributed equally to this work Correspondence to: Qiong Yu, email: yuqiong@jlu.edu.cn Keywords: papillary thyroid carcinoma, nodular goiter, VEGFA, SNPs, Han Chinese Received: September 01, 2016      Accepted: January 06, 2017      Published: February 02, 2017 ABSTRACT The aim of the present study was to investigate whether genetic variants in the vascular endothelial growth factor A gene ( VEGFA ) were risk factors for papillary thyroid carcinoma (PTC) or nodular goiter (NG) in Han Chinese. A total of 2,319 subjects (861 PTC patients, 562 NG patients, and 896 healthy controls) were included. Five tag single nucleotide polymorphisms (tagSNPs: rs3024997, rs3025040, rs833070, rs25648, and rs10434) in VEGFA were genotyped. SNP rs3025040 T allele was associated with a decreased risk of NG ( P <0.05). SNP rs3024997 was associated with an increased risk of PTC ( P <0.05) and NG ( P <0.001) when an over-dominant model (AA+GG vs . AG) was considered. PTC patients carry the less frequent TT genotype (compared to the CC genotype) ( P <0.05) of SNP rs3025040. Likewise, NG patients have the less frequent TC genotype compared to the CC ( P <0.05). No significant association of SNPs rs833070, rs25648, and rs10434 with PTC or NG was observed. Haplotypes AT (rs3024997 and rs3025040) and GTA (rs10434, rs3025040, and rs3024997) showed a lower risk for NG ( P <0.01 and P <0.05, respectively), while haplotypes GTT (rs833070, rs3025040, and rs3024997) and GGGT (rs833070, rs10434, rs3024997, and rs3025040) predicted the risk of progression to NG (both P <0.05). Haplotype AGAC (rs833070, rs10434, rs3024997, and rs3025040) conferred protection for PTC ( P <0.05). In summary, this study indicated for the first time that SNPs rs3024997 and rs3025040 in VEGFA were significantly associated with PTC and/or NG. Haplotypes of the VEGFA may influence the risk of PTC and NG.