Bingül İlknur, Vural Pervin, Doğru-Abbasoğlu Semra, Çil Esra, Uysal Müjdat
Istanbul Faculty of Medicine, Department of Biochemistry, Istanbul University, Istanbul, Turkey.
II. Internal Medicine Clinic, Department of Endocrinology, Şişli Etfal Education and Research Hospital, Istanbul, Turkey.
J Clin Lab Anal. 2017 Nov;31(6). doi: 10.1002/jcla.22110. Epub 2016 Dec 7.
Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. Vascular endothelial growth factor (VEGF) is a mediator implicated with cell proliferation, differentiation and migration, and monocyte/macrophage chemotaxis. In present study, we aimed to investigate the relationship between VEGF gene polymorphisms (G+405C, T-460C, and A-2578C) and PTC susceptibility.
DNA was isolated from peripheral blood leukocytes of 127 patients with PTC and 203 healthy controls. Genotyping was performed by real-time PCR. Association of genotypes with susceptibility of PTC was analyzed with multivariate logistic regression adjusted for age, gender and smoking status.
In G+405C polymorphism, the frequencies of C allele (related with increased VEGF production) and combined CG+CC genotype were found to be higher (3.5 and 5-fold, respectively) among patients with PTC than controls (P<.001). However, VEGF T-460C and A-2578C polymorphisms are not associated with PTC risk. There was no relationship between VEGF polymorphisms and clinical/laboratory parameters of PTC. Haplotype analysis demonstrated that there was a strong linkage disequilibrium (LD) between -460/-2578 (D'=.89, r =.79), weak LD between +405/-460 (D'=.422, r =.035), and +405/-2578 (D'=.43, r =.038) locuses. Additionally, the +405/-460/-2578 GTA haplotype was found to be protective, whereas CTA haplotype to be related with increased PTC risk. As a conclusion, we suggest that VEGF G+405C polymorphism is associated with increased risk of PTC.
甲状腺乳头状癌（PTC）是最常见的内分泌恶性肿瘤。血管内皮生长因子（VEGF）是一种与细胞增殖、分化、迁移以及单核细胞/巨噬细胞趋化性有关的介质。在本研究中，我们旨在探讨VEGF基因多态性（G+405C、T-460C和A-2578C）与PTC易感性之间的关系。
从127例PTC患者和203例健康对照者的外周血白细胞中提取DNA。通过实时PCR进行基因分型。采用多因素logistic回归分析调整年龄、性别和吸烟状态后基因型与PTC易感性的关联。
在G+405C多态性中，发现PTC患者中与VEGF产生增加相关的C等位基因频率以及CG+CC基因型频率分别比对照组高3.5倍和5倍（P<0.001）。然而，VEGF的T-460C和A-2578C多态性与PTC风险无关。VEGF多态性与PTC的临床/实验室参数之间没有关系。单倍型分析表明，-460/-2578位点之间存在强连锁不平衡（LD）（D'=0.89，r=0.79），+405/-460位点之间存在弱LD（D'=0.422，r=0.035），+405/-2578位点之间存在弱LD（D'=0.43，r=0.038）。此外，发现+405/-460/-2578 GTA单倍型具有保护作用，而CTA单倍型与PTC风险增加有关。总之，我们认为VEGF G+405C多态性与PTC风险增加有关。
