Research Group of Personalized Diet, Korea Food Research Institute, Wanju-gun 55365, Jeollabuk-do, Korea.
Department of Food Biotechnology, Korea University of Science & Technology, Wanju-gun 55365, Jeollabuk-do, Korea.
Nutrients. 2022 Aug 6;14(15):3222. doi: 10.3390/nu14153222.
Over the last several decades, there has been a considerable growth in type 2 diabetes (T2DM) in Asians. A pathophysiological mechanism in Asian T2DM is closely linked to low insulin secretion, β-cell mass, and inability to compensate for insulin resistance. We hypothesized that genetic variants associated with lower β-cell mass and function and their combination with unhealthy lifestyle factors significantly raise T2DM risk among Asians. This hypothesis was explored with participants aged over 40. Participants were categorized into T2DM (case; n = 5383) and control (n = 53,318) groups. The genetic variants associated with a higher risk of T2DM were selected from a genome-wide association study in a city hospital-based cohort, and they were confirmed with a replicate study in Ansan/Ansung plus rural cohorts. The interacted genetic variants were identified with generalized multifactor dimensionality reduction analysis, and the polygenic risk score (PRS)-nutrient interactions were examined. The 8-SNP model was positively associated with T2DM risk by about 10 times, exhibiting a higher association than the 20-SNP model, including all T2DM-linked SNPs with p < 5 × 10−6. The SNPs in the models were primarily involved in pancreatic β-cell growth and survival. The PRS of the 8-SNP model interacted with three lifestyle factors: energy intake based on the estimated energy requirement (EER), Western-style diet (WSD), and smoking status. Fasting serum glucose concentrations were much higher in the participants with High-PRS in rather low EER intake and high-WSD compared to the High-EER and Low-WSD, respectively. They were shown to be higher in the participants with High-PRS in smokers than in non-smokers. In conclusion, the genetic impact of T2DM risk was mainly involved with regulating pancreatic β-cell mass and function, and the PRS interacted with lifestyles. These results highlight the interaction between genetic impacts and lifestyles in precision nutrition.
在过去几十年中，亚洲 2 型糖尿病（T2DM）的发病率显著上升。亚洲人 T2DM 的病理生理学机制与胰岛素分泌减少、β细胞数量减少以及无法代偿胰岛素抵抗密切相关。我们假设，与较低的β细胞数量和功能相关的遗传变异及其与不健康生活方式因素的结合，会显著增加亚洲人患 T2DM 的风险。本研究通过对年龄超过 40 岁的参与者进行了研究，来验证这一假说。将参与者分为 T2DM（病例；n=5383）和对照组（n=53318）。选择来自城市医院队列的全基因组关联研究中与 T2DM 风险较高相关的遗传变异，并在安山/安城及农村队列的重复研究中进行验证。通过广义多因子降维分析识别相互作用的遗传变异，并检验多基因风险评分（PRS）与营养素的相互作用。8-SNP 模型与 T2DM 风险呈正相关，其关联程度约为 10 倍，比包含所有 p<5×10−6的与 T2DM 相关的 20-SNP 模型具有更高的关联。模型中的 SNP 主要涉及胰岛β细胞的生长和存活。8-SNP 模型的 PRS 与三种生活方式因素相互作用：基于估计能量需求（EER）的能量摄入、西式饮食（WSD）和吸烟状况。与高-EER 和低-WSD 相比，高 PRS 且低 EER 摄入和高 WSD 的参与者空腹血糖浓度明显更高。与非吸烟者相比，吸烟者中高 PRS 参与者的空腹血糖浓度更高。总之，T2DM 风险的遗传影响主要与调节胰岛β细胞数量和功能有关，PRS 与生活方式相互作用。这些结果强调了遗传影响和生活方式在精准营养中的相互作用。
