Environmental Research Center, Duke Kunshan University, Kunshan, China.
School of Medicine, Yale University, New Haven, Connecticut, USA.
Rejuvenation Res. 2021 Feb;24(1):49-61. doi: 10.1089/rej.2019.2301. Epub 2020 May 29.
Residential greenness is an important environmental factor that is strongly associated with mortality. To our knowledge, there was no previous study on the gene-environment interaction analysis between residential greenness and forkhead box O () gene, a candidate longevity gene. Our sample consisted of 3179 participants aged 65 and older from the Chinese Longitudinal Healthy Longevity Survey. Residential greenness was measured by satellite-derived normalized difference vegetation index (NDVI) using a 500-m radius around each residential location. Contemporaneous NDVI, cumulative NDVI, and changes in NDVI over time were calculated. We used Cox-proportional hazard regression models to assess the main effect and gene-environment interaction effect of single nucleotide polymorphism (SNP) and residential greenness on mortality. We found that participants carrying two minor alleles of the three studied SNPs had lower mortality risk than those without minor allele (hazard ratio [HR]: 0.803 95% confidence interval [CI]: 0.654-0.987 for rs4946936, HR: 0.807 95% CI: 0.669-0.974 for rs2802292, HR: 0.803 95% CI: 0.666-0.968 for rs2253310). We found no difference in mortality among the genotypes of the other three SNPs (rs17630266, rs2755213, or rs2755209). Higher contemporaneous NDVI was associated with lower mortality risk (HR: 0.887 95% CI: 0.863-0.911 for 0.1-U of NDVI). The protective effect of both contemporaneous NDVI and cumulative NDVI was stronger for two minor allele carriers compared with zero minor allele carriers of the three SNPs. Compared with the zero minor allele genotype of the three SNPs, the protective effect on the mortality risk of minor allele homozygotes also increased with the increasing NDVI level at percentile 25, 50, and 75 (interaction term coefficient < 0.05). We found gene-environment interaction between and residential greenness on mortality in this population study. A higher level of greenness may interact with pathways.
居住绿化是一个重要的环境因素，与死亡率密切相关。据我们所知，以前没有研究过居住绿化与叉头框 O()基因（候选长寿基因）之间的基因-环境交互作用。我们的样本包括来自中国长寿纵向研究的 3179 名 65 岁及以上的参与者。居住绿化通过卫星衍生的归一化差异植被指数（NDVI）进行测量，使用每个居住地点周围 500 米的半径。同时计算 NDVI、累积 NDVI 和随时间变化的 NDVI 变化。我们使用 Cox 比例风险回归模型来评估单核苷酸多态性 (SNP) 和居住绿化对死亡率的主要影响和基因-环境相互作用效应。我们发现，与没有携带次要等位基因的参与者相比，携带三个研究 SNP 中的两个次要等位基因的参与者的死亡率风险较低（rs4946936 的风险比 [HR]：0.803，95%置信区间 [CI]：0.654-0.987，rs2802292 的 HR：0.807，95%CI：0.669-0.974，rs2253310 的 HR：0.803，95%CI：0.666-0.968）。在其他三个 SNP(rs17630266、rs2755213 或 rs2755209)的基因型中，死亡率没有差异。更高的同时 NDVI 与更低的死亡率风险相关（0.1-U NDVI 的 HR：0.887，95%CI：0.863-0.911）。与三个 SNP 中没有携带三个 SNP 中的两个次要等位基因的参与者相比，同时 NDVI 和累积 NDVI 的保护作用对两个次要等位基因携带者更强。与三个 SNP 的零次要等位基因基因型相比，次要等位基因纯合子的死亡率风险保护作用也随着 25%、50%和 75%分位数的 NDVI 水平的增加而增加（交互项系数 <0.05）。在这项人群研究中，我们发现与死亡率的基因-环境相互作用。更高的绿化水平可能与 途径相互作用。
