Division of Vitreous and Retina, Department of Ophthalmology, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon 16247, Korea.
Food and Nutrition, Obesity/Diabetes Research Center, Institute of Basic Science, Hoseo University, Asan 31499, Korea.
Nutrients. 2020 Nov 17;12(11):3534. doi: 10.3390/nu12113534.
Age-related cataract (ARC) development is associated with loss of crystalline lens transparency related to interactions between genetic and environmental factors. We hypothesized that polygenetic risk scores (PRS) of the selected genetic variants among the ARC-related genes might reveal significant genetic impacts on ARC risk, and the PRS might have gene-gene and gene-lifestyle interactions. We examined the hypothesis in 1972 and 39,095 subjects aged ≥50 years with and without ARC, respectively, in a large-scale hospital-based cohort study conducted from 2004 to 2013. Single nucleotide polymorphisms (SNPs) of the genes related to ARC risk were identified, and polygenetic risk scores (PRS) were generated based on the results of a generalized multifactor dimensionality reduction analysis. Lifestyle interactions with PRS were evaluated. The PRS derived from the best model included the following six SNPs related to crystallin metabolism: _rs1417380362, _rs2070894, _rs55785344, _rs879419608, _rs322348, and _rs200053781. The risk of ARC in the high-PRS group was 2.47-fold higher than in the low-PRS group after adjusting for confounders. Age, blood pressure, and glycemia interacted with PRS to influence the risk of ARC: the incidence of ARC was much higher in the elderly (≥65 years) and individuals with hypertension or hyperglycemia. The impact of PRS on ARC risk was greatest in middle-aged individuals with hypertension or hyperglycemia. Na, coffee, and a Western-style diet intake also interacted with PRS to influence ARC risk. ARC risk was higher in the high-PRS group than in the low-PRS group, and high Na intake, Western-style diet, and low coffee intake elevated its risk. In conclusion, ARC risk had a positive association with PRS related to crystallin metabolism. The genetic impact was greatest among those with high Na intake or hypertension. These results can be applied to precision nutrition interventions to prevent ARC.
年龄相关性白内障 (ARC) 的发生与晶状体透明度丧失有关，这与遗传和环境因素的相互作用有关。我们假设 ARC 相关基因中选定遗传变异的多基因风险评分 (PRS) 可能会揭示对 ARC 风险的显著遗传影响，并且 PRS 可能具有基因-基因和基因-生活方式相互作用。我们在 2004 年至 2013 年期间进行的一项大规模基于医院的队列研究中，分别对 1972 名年龄≥50 岁的 ARC 患者和 39095 名无 ARC 患者进行了假设检验。确定了与 ARC 风险相关的基因的单核苷酸多态性 (SNP)，并基于广义多因子降维分析的结果生成了多基因风险评分 (PRS)。评估了 PRS 与生活方式的相互作用。最佳模型得出的 PRS 包括以下与晶状体代谢相关的六个 SNP：_rs1417380362、_rs2070894、_rs55785344、_rs879419608、_rs322348 和 _rs200053781。在调整混杂因素后，高 PRS 组的 ARC 风险是低 PRS 组的 2.47 倍。年龄、血压和血糖与 PRS 相互作用影响 ARC 风险：老年人（≥65 岁）和高血压或高血糖个体的 ARC 发生率更高。PRS 对 ARC 风险的影响在高血压或高血糖的中年个体中最大。Na、咖啡和西式饮食的摄入也与 PRS 相互作用影响 ARC 风险。高 PRS 组的 ARC 风险高于低 PRS 组，高 Na 摄入、西式饮食和低咖啡摄入会增加其风险。总之，ARC 风险与晶状体代谢相关的 PRS 呈正相关。遗传影响在高 Na 摄入或高血压患者中最大。这些结果可应用于精准营养干预以预防 ARC。
Zotero 插件
