Istanbul University, Istanbul Faculty of Medicine, Department of Biochemistry, Istanbul, Turkey.
Istanbul University, Istanbul Faculty of Medicine, Department of Biochemistry, Istanbul, Turkey.
Int Immunopharmacol. 2014 Jan;18(1):198-202. doi: 10.1016/j.intimp.2013.11.017. Epub 2013 Dec 2.
Endothelin 1 (EDN1) is a strong angiogenic and mitogenic factor, playing a key role in hypervascularization, thyroid follicle cell hyperplasia, and lymphocyte infiltration in the thyroid gland of patients with Graves' disease (GD). EDN1 induces angiogenesis and mitogenesis via endothelin receptor type A (EDNRA). This study examined the possible association of EDN1 (G5665T and T-1370G) and EDNRA (C+70G and G-231A) single nucleotide polymorphisms (SNPs) with the occurrence of GD, and evaluates the relationship between genotypes and clinical/laboratory manifestations of GD.
We analyzed genotype and allele distributions of EDN1 and EDNRA polymorphisms in 165 patients with GD and 181 healthy controls by real-time PCR combined with melting curve analysis.
No significant associations between GD and variant alleles of the studied polymorphisms were observed. However, the anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-TG) levels in EDN1 G5665T GG genotype were higher than those in T allele carriers (GT+TT) (p=0.001 and p=0.026, respectively). In addition, anti-TPO levels in EDN1 T-1370G wild-type homozygous patients were found to be higher than in mutant gene carrying patients (GT+GG) (p=0.006). The presence of EDNRA+70G allele was associated with 3.37-fold increased risk for development of ophthalmopathy in GD patients (p=0.009).
Although there were no associations between EDN1 (G5665T and T-1370G) and EDNRA (C+70G and G-231A) SNPs and susceptibility to GD, EDN1 G5665T and T-1370G polymorphisms were related to alterations of autoantibody production and EDNRA C+70G polymorphism is related with increased risk for ophthalmopathy in GD patients.
内皮素 1（EDN1）是一种强有力的血管生成和有丝分裂原，在格雷夫斯病（GD）患者甲状腺中的血管生成、甲状腺滤泡细胞增生和淋巴细胞浸润中发挥关键作用。EDN1 通过内皮素受体 A（EDNRA）诱导血管生成和有丝分裂。本研究探讨了 EDN1（G5665T 和 T-1370G）和 EDNRA（C+70G 和 G-231A）单核苷酸多态性（SNP）与 GD 发生的可能相关性，并评估了基因型与 GD 临床/实验室表现之间的关系。
通过实时 PCR 结合熔解曲线分析，对 165 例 GD 患者和 181 例健康对照者的 EDN1 和 EDNRA 多态性基因型和等位基因分布进行分析。
未观察到 GD 与研究多态性的变异等位基因之间存在显著相关性。然而，EDN1 G5665T GG 基因型的甲状腺过氧化物酶（anti-TPO）和甲状腺球蛋白（anti-TG）水平高于 T 等位基因携带者（GT+TT）（p=0.001 和 p=0.026）。此外，EDN1 T-1370G 野生型纯合患者的 anti-TPO 水平高于突变基因携带者（GT+GG）（p=0.006）。EDNRA+70G 等位基因的存在与 GD 患者眼病发生的风险增加 3.37 倍相关（p=0.009）。
尽管 EDN1（G5665T 和 T-1370G）和 EDNRA（C+70G 和 G-231A）SNP 与 GD 易感性之间没有关联，但 EDN1 G5665T 和 T-1370G 多态性与自身抗体产生的改变有关，EDNRA C+70G 多态性与 GD 患者眼病发生的风险增加有关。
