与铁变态相关的 CPT1A 和 GDF15 基因多态性是肺腺癌的危险因素：一项病例对照研究。

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS ACS Applied Bio Materials Pub Date : 2024-10-12 DOI:10.1016/j.gene.2024.149002

Xing Zhang, Rong Wang, Xia Zhang, Yanli Yang, Ruifen Tian

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引用次数: 0

摘要

背景：铁蛋白沉积不仅是炎症的结果，也是一个动态过程。最近的生物信息学分析表明，铁蛋白沉积相关基因可能与肺腺癌（LUAD）有关。CPT1A和GDF15对铁蛋白沉积过程和炎症的发展至关重要；然而，很少有研究关注这些基因在LUAD患者中的突变水平：方法：利用 Mass ARRAY 平台对 320 对 LUAD 患者和对照组进行了 CPT1A 和 GDF15 候选 SNPs 的基因分型。此外，通过 qRT-PCR 和 ELISA 验证了 CPT1A 和 GDF15 在 LUAD 病例和健康对照组中的不同表达：结果发现：rs80356779 G > A、rs3019594 C > T、rs888663 T > G 和 rs4808793 G > C 均表现出患病风险增加（p A. G > G）、在显性和加性模型下，rs888663 T > G 和 rs4808793 G > C 与 LUAD 易感性相关（在所有三个模型中，p T 与疾病风险升高相关（p A 和 rs3019594 C > T 与 wile 型相比，CPT1A 的表达和血清浓度较低；rs888663 T > G 和 rs4808793 G > C 患者的血清和 GDF15 表达水平较高。结论研究结果为铁蛋白沉积在 LUAD 中的作用提供了新线索，也为筛查易感人群提供了新的潜在靶点。

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Ferroptosis related CPT1A and GDF15 gene polymorphisms are risk factors for lung adenocarcinoma: A case-control study

Background

Ferroptosis is not only a consequence of inflammation, but also a dynamic process. Recent bioinformatics analysis suggests that ferroptosis related genes might be associated with lung adenocarcinoma (LUAD). CPT1A and GDF15 are critical for the process of ferroptosis and development of inflammation; however, little study focused on the mutation level of these genes in patients with LUAD.

Methods

The candidate SNPs in CPT1A and GDF15 were genotyped in 320 pairs of LUAD patients and controls using Mass ARRAY platform. Moreover, the different expression of CPT1A and GDF15 in LUAD cases and healthy controls were validated by qRT-PCR and ELISA.

Results

The rs80356779 G > A, rs3019594 C > T, rs888663 T > G and rs4808793 G > C all exhibited an increased risk of the disease (p < 0.05). Moreover, the rs80356779-GA, rs3019594-TT, rs888663-TG and rs4808793-CC genotypes were all related to different levels of increase in LUAD risk (p < 0.05). Genetic model results showed that rs80356779 G > A, rs888663 T > G and rs4808793 G > C were associated with LUAD susceptibility under dominant and additive models (p < 0.05), while rs3019594 C > T was correlated with an elevated risk of the disease in all three models (p < 0.05). Additionally, patients with rs80356779 G > A and rs3019594 C > T exhibited lower expression and serum concentration of CPT1A compared with wile types, and patients with rs888663 T > G and rs4808793 G > C exhibited higher serum and expression level of GDF15.