载脂蛋白 E 基因 ε4 等位基因对南方汉族人群血脂谱及心脑血管疾病和肿瘤发病风险的影响。
Effects of APOE gene ε4 allele on serum lipid profiles and risk of cardiovascular disease and tumorigenesis in southern Chinese population.
机构信息
Center for Precision Medicine, Meizhou People's Hospital, Meizhou, China.
Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translational Research of Hakka Population, Meizhou, China.
出版信息
World J Surg Oncol. 2022 Sep 3;20(1):280. doi: 10.1186/s12957-022-02748-2.
BACKGROUND
Human apolipoprotein E (APOE) polymorphisms are attributable to the presence of three common alleles, namely, ε2, ε3, and ε4, which generate six genotypes, viz, E2/E2, E2/E3, E3/E3, E3/E4, E4/E4, and E2/E4. APOE polymorphisms are associated with all types of tumors and cardiovascular diseases (CVD). However, the relationship between the type of APOE polymorphisms and tumorigenesis remains debatable. Therefore, we aimed to investigate the role of APOE polymorphisms on the tumor with or without CVD in southern China.
METHODS
A total of 1438 participants were categorized into 4 groups: 409 patients with tumor, 369 patients with CVD, 338 patients with both tumor and CVD, and 322 controls. APOE polymorphisms were determined by genotyping assay. The factors influencing tumor patients with or without CVD were also analyzed by logistic regression analysis.
RESULTS
The present study involved different types of solid tumors. Lung cancer was the most common cancer (20.2%, 151/747), followed by colorectal (17%, 127/747), esophageal (9.8%, 73/747), and liver (8.7%, 65/747) cancers. E3/E3 was the most frequent genotype, and ɛ3 was the greatest allele frequency in our study population. The frequencies of the E3/E3, E3/E4, E2/E3, E2/E4, E4/E4, and E2/E2 genotypes in tumor patients were 76.97% (575/747), 14.19% (106/747), 6.83% (51/747), 1.2% (9/747), 0.4% (3/747), and 0.4% (3/747), respectively. Tumor patients carrying ε3 with or without CVD showed higher levels of TG, TC, and LDL-C and lower levels of HDL-C compared to the controls carrying ε3. On the other hand, the tumor patients carrying ε4 with or without CVD showed higher levels of TG and LDL-C and lower levels of HDL-C (all P < 0.05). The frequency of APOE ε4 allele and the E3/E4 genotype was relatively greater in tumor or CVD patients (P < 0.001). In addition, ε4 allele acted as an independent risk factor for tumor patients group (P = 0.037, adjusted OR = 1.92, 95% CI 1.04-3.55) and tumor + CVD patients group (P = 0.012, adjusted OR = 2.53, 95% CI 1.22-5.23).
CONCLUSIONS
Individuals carrying ε4 are at a higher risk of tumor with or without CVD, and APOE polymorphisms affect the serum lipid profiles.
背景
人类载脂蛋白 E（APOE）多态性归因于三个常见等位基因的存在，即 ε2、ε3 和 ε4，它们产生六种基因型，即 E2/E2、E2/E3、E3/E3、E3/E4、E4/E4 和 E2/E4。APOE 多态性与所有类型的肿瘤和心血管疾病（CVD）有关。然而，APOE 多态性的类型与肿瘤发生之间的关系仍存在争议。因此，我们旨在研究 APOE 多态性对中国南方肿瘤伴或不伴 CVD 的影响。
方法
共纳入 1438 名参与者，分为 4 组：409 例肿瘤患者、369 例 CVD 患者、338 例肿瘤合并 CVD 患者和 322 例对照。通过基因分型检测 APOE 多态性。通过逻辑回归分析还分析了影响有或无 CVD 的肿瘤患者的因素。
结果
本研究涉及不同类型的实体瘤。肺癌最常见（20.2%，151/747），其次是结直肠癌（17%，127/747）、食管癌（9.8%，73/747）和肝癌（8.7%，65/747）。E3/E3 是最常见的基因型，在我们的研究人群中，ɛ3 是最大的等位基因频率。肿瘤患者中 E3/E3、E3/E4、E2/E3、E2/E4、E4/E4 和 E2/E2 基因型的频率分别为 76.97%（575/747）、14.19%（106/747）、6.83%（51/747）、1.2%（9/747）、0.4%（3/747）和 0.4%（3/747）。患有 CVD 的携带 ε3 的肿瘤患者与携带 ε3 的对照组相比，甘油三酯（TG）、总胆固醇（TC）和低密度脂蛋白胆固醇（LDL-C）水平更高，高密度脂蛋白胆固醇（HDL-C）水平更低。另一方面，患有 CVD 的携带 ε4 的肿瘤患者与携带 ε4 的对照组相比，TG 和 LDL-C 水平更高，HDL-C 水平更低（均 P < 0.05）。APOE ε4 等位基因和 E3/E4 基因型在肿瘤或 CVD 患者中更为常见（P < 0.001）。此外，ε4 等位基因是肿瘤患者组（P = 0.037，调整 OR = 1.92，95%CI 1.04-3.55）和肿瘤+CVD 患者组（P = 0.012，调整 OR = 2.53，95%CI 1.22-5.23）的独立危险因素。
结论
携带 ε4 的个体患肿瘤伴或不伴 CVD 的风险更高，APOE 多态性影响血清脂质谱。
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