味觉SNP与环境因素对老年群体认知功能的影响

Influence of Taste-Related SNPs and Environmental Factors on Cognitive Function in Elderly Populations

关键词:  味觉功能  认知功能  GMDR  味觉SNP  健康长寿

Key words:  Taste function  Cognitive function  GMDR  Taste-related SNPs  Healthy longevity

摘要:

目的 本研究旨在探讨遗传因素及其与环境因素的交互作用对红水河流域老年人认知功能的影响。方法 采用病例-对照设计,选取红水河流域老年群体,分为认知正常组和认知损害组进行比较。通过提取外周血DNA检测味觉相关的单核苷酸多态性(SNP),评估各SNP与味觉感知和认知状态的关联,并采用多因素模型分析基因-基因及基因-环境交互效应对认知状态的影响。结果 多个SNP位点与老年人味觉功能显著相关,苦味受体基因TAS2R38 rs10246939位点在显性遗传模型下显著增加认知障碍发生风险,而CLEC5A rs1285950位点杂合基因型在认知损害组中频率更高,可能是认知损害的危险因素。广义多因子降维法(GMDR)筛选出的最佳AGK、DENND11和CLEC5A基因的四位点模型以及包含味觉评分和性别的SNP-环境交互模型均对认知功能具有良好的预测效能。结论 红水河流域老年人群的认知功能受多基因遗传因素影响,味觉相关SNP及其与味觉功能和性别等环境因素的交互作用在其中发挥重要作用。

Abstract:

Objective: This study aims to investigate the impact of genetic factors and their interactions with environmental factors on cognitive function among the elderly in the Red River Basin. Methods: A case-control design was employed, involving elderly individuals from the Red River Basin, divided into cognitively normal and cognitively impaired group for comparison. Peripheral blood DNA was extracted to detect taste-related single nucleotide polymorphisms (SNPs). The associations between each SNP with taste perception and cognitive status were evaluated. Multifactorial models were utilized to analyze gene-gene and gene-environment interactions. Results: Several SNP loci were significantly associated with taste function in the elderly. The TAS2R38 rs10246939 locus, a bitter taste receptor gene, was found to significantly increase the risk of cognitive impairment under the dominant genetic model. In contrast, the heterozygous genotype of the CLEC5A rs1285950 locus was more frequent in the cognitively impaired group, suggesting it may be a potential risk factor for cognitive decline. The best four-locus model involving the AGK, DENND11, and CLEC5A genes, identified through generalized multifactor dimensionality reduction (GMDR), as well as a SNP–environment interaction model incorporating taste score and sex, both demonstrated good predictive performance for cognitive function. Conclusion: The cognitive function of the elderly population in the Hongshui River Basin is influenced by multiple genetic factors. Taste-related SNPs and their interactions with environmental factors such as taste function and gender play significant roles in this process.