Background: The vascular endothelial growth factor-A (VEGFA) family of cytokines regulates proliferation, angiogenesis, and migration of endothelial cells, increases vascular permeability, and controls thrombogenicity. Recent studies have suggested that the VEGFA gene plays an important role in the pathogenesis of metabolic syndrome and its related disorders. Dietary diversity score (DDS) has also been shown to have potential favorable effects against features of metabolic syndrome. This study examined the interactions between +405 VEGFA C/G (rs2010963) polymorphism and DDS on the metabolic and biochemical profile of metabolic syndrome. Therefore, in the current study, we aimed to evaluate the interaction between DDS and VEGFA rs2010963 gene polymorphisms in modification of metabolic risk factors including serum lipids, blood pressure, serum adiponectin, and matrix metalloproteinase (MMP)-3 concentrations in patients with metabolic syndrome. Methods and Materials: In the current cross-sectional study, 254 patients with metabolic syndrome were recruited. Measurements of blood pressure, anthropometric parameters, and dietary intakes were performed and the DDS was calculated. Biochemical variables including serum adiponectin concentrations, lipid profile, serum glucose, and MMP-3 concentrations were measured by enzyme-linked immunosorbent assay method (ELISA) and enzymatic colorimetric methods. Determination of +405 C/G VEGFA gene polymorphisms was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Results: Patients in the lowest DDS quartile had higher insulin and homeostatic model assessment of insulin resistance (HOMA-IR), while patients in the highest DDS quartile had higher quantitative insulin check index (QUICKI; p < 0.05). Higher serum triglyceride and systolic blood pressure (SBP) values and lower serum adiponectin concentrations were also observed in lower DDS quartiles (p < 0.05). Patients with the CC genotype in the VEGFA rs2010963 polymorphism had significantly higher body mass index (BMI), fasting blood glucose, aspartate aminotransferase (AST), and alanine aminotransferase (ALT; p < 0.05) compared to patients with the other 2 genotypes. In lower quartiles of DDS, 30% of patients with metabolic syndrome had the GG genotype, while 30.4 and 30.8% of patients with metabolic syndrome in higher DDS quartiles had GC and CC genotypes, respectively (p = 0.04). Conclusion: Our study found lower insulin resistance, serum triglyceride, and SBP and higher adiponectin concentrations among patients with metabolic syndrome in highest quartiles of DDS. Moreover, patients with the CC genotype were more likely to have higher BMI, fasting blood glucose, AST, and ALT. This significant interaction gives a possible evidence of a VEGFA-DDS association that may be relevant to metabolic syndrome. Further studies are warranted to clarify the underlying mechanisms of these interactions.

中文翻译：

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血管内皮生长因子-A (rs2010963) 基因多态性与代谢综合征患者心血管危险因素饮食多样性评分之间的相互作用

背景：血管内皮生长因子-A (VEGFA) 细胞因子家族调节内皮细胞的增殖、血管生成和迁移，增加血管通透性，并控制血栓形成。最近的研究表明，VEGFA 基因在代谢综合征及其相关疾病的发病机制中起重要作用。饮食多样性评分 (DDS) 也已被证明对代谢综合征的特征具有潜在的有利影响。本研究检查了 +405 VEGFA C/G (rs2010963) 多态性和 DDS 之间的相互作用，对代谢综合征的代谢和生化特征。因此，在目前的研究中，我们旨在评估 DDS 和 VEGFA rs2010963 基因多态性在改变代谢危险因素（包括血脂、血压、代谢综合征患者血清脂联素和基质金属蛋白酶（MMP）-3浓度。方法和材料：在目前的横断面研究中，招募了 254 名代谢综合征患者。测量血压、人体测量参数和饮食摄入量并计算 DDS。通过酶联免疫吸附测定法 (ELISA) 和酶促比色法测量生化变量，包括血清脂联素浓度、脂质谱、血清葡萄糖和 MMP-3 浓度。使用聚合酶链反应限制性片段长度多态性 (PCR-RFLP) 技术确定 +405 C/G VEGFA 基因多态性。结果：DDS 最低四分位数的患者具有较高的胰岛素和胰岛素抵抗稳态模型评估 (HOMA-IR)，而 DDS 最高四分位数的患者具有较高的定量胰岛素检查指数 (QUICKI；p < 0.05)。在较低的 DDS 四分位数中也观察到较高的血清甘油三酯和收缩压 (SBP) 值以及较低的血清脂联素浓度 (p < 0.05)。与其他 2 种基因型患者相比，具有 VEGFA rs2010963 多态性中 CC 基因型的患者的体重指数 (BMI)、空腹血糖、天冬氨酸转氨酶 (AST) 和丙氨酸转氨酶 (ALT；p < 0.05) 显着更高。在 DDS 的较低四分位数中，30% 的代谢综合征患者具有 GG 基因型，而在较高 DDS 四分位数中，30.4% 和 30.8% 的代谢综合征患者具有 GC 和 CC 基因型，分别（p = 0.04）。结论：我们的研究发现，在 DDS 最高四分位数的代谢综合征患者中，胰岛素抵抗、血清甘油三酯和 SBP 较低，脂联素浓度较高。此外，具有 CC 基因型的患者更有可能具有更高的 BMI、空腹血糖、AST 和 ALT。这种显着的相互作用提供了可能与代谢综合征相关的 VEGFA-DDS 关联的可能证据。需要进一步的研究来阐明这些相互作用的潜在机制。AST 和 ALT。这种显着的相互作用提供了可能与代谢综合征相关的 VEGFA-DDS 关联的可能证据。需要进一步的研究来阐明这些相互作用的潜在机制。AST 和 ALT。这种显着的相互作用提供了可能与代谢综合征相关的 VEGFA-DDS 关联的可能证据。需要进一步的研究来阐明这些相互作用的潜在机制。