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CYP1A1、谷胱甘肽S-转移酶(GST)、72TP53基因多态性与甲状腺结节发病机制的关系。

Involvement of CYP1A1, GST, 72TP53 polymorphisms in the pathogenesis of thyroid nodules.

作者信息

Reis A A S, Silva D M, Curado M P, da Cruz A D

机构信息

Universidade Federal de Goiás, Goiânia, GO, Brasil.

出版信息

Genet Mol Res. 2010 Nov 16;9(4):2222-9. doi: 10.4238/vol9-4gmr807.

Abstract

Specific genotypes appear to be related to the development of thyroid disease. We examined whether polymorphisms of the genes CYP1A1, GSTM1, GSTT1, and TP53 at codon 72 are associated with increased risk for thyroid nodules. Blood samples were obtained from 122 thyroid patients with nodules and from 134 healthy control individuals from Goiânia city, GO, Brazil. We found no significant association of CYP1A1m1 and CYP1A1m2 genotypes with thyroid diseases (P > 0.05). The null genotypes of GSTM1 and GSTT1 genes were predominant in patients with nodules, indicating that individuals that possess these genotypes have a predisposition for thyroid disease. The genotype p53Arg Arg was associated with a low risk for thyroid cancer (OR = 0.15; P < 0.0001), indicating that the arginine allele in homozygosis could have a protective effect against carcinogenesis. On the other hand, the p53ArgPro genotype was significantly associated with malignant neoplastic nodules (OR = 3.65; P = 0.001). Interindividual variation in susceptibility to thyroid diseases could provide new perspectives for early diagnosis, prognosis and treatment, indicating which patients with thyroid nodules will benefit from treatment, depending on specific polymorphic profiles.

摘要

特定的基因型似乎与甲状腺疾病的发生有关。我们研究了细胞色素P450 1A1(CYP1A1)、谷胱甘肽S转移酶M1(GSTM1)、谷胱甘肽S转移酶T1(GSTT1)基因多态性以及第72位密码子的TP53基因多态性是否与甲状腺结节风险增加相关。从巴西戈亚尼亚市的122例甲状腺结节患者和134例健康对照个体中采集血样。我们发现CYP1A1m1和CYP1A1m2基因型与甲状腺疾病无显著相关性(P>0.05)。GSTM1和GSTT1基因的无效基因型在结节患者中占主导地位,表明具有这些基因型的个体易患甲状腺疾病。p53基因的Arg Arg基因型与甲状腺癌低风险相关(比值比[OR]=0.15;P<0.0001),表明纯合子中的精氨酸等位基因可能对致癌作用具有保护作用。另一方面,p53基因的ArgPro基因型与恶性肿瘤结节显著相关(OR=3.65;P=0.001)。甲状腺疾病易感性的个体差异可为早期诊断、预后和治疗提供新的视角,根据特定的多态性谱表明哪些甲状腺结节患者将从治疗中获益。

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