脂质分布受遗传和环境因素的影响。在先前的研究中,APOA4-APOA5-ZPR1-BUD13基因簇中的遗传变异和异常睡眠持续时间被独立地鉴定为与脂质相关。我们旨在调查睡眠持续时间是否改变了与纵向脂质变化的遗传关联。
四个单核苷酸多态性(SNPs),在东风-同济(DFTJ)队列的8648名明显健康的受试者中,对APOA4-APOA5-ZPR1-BUD13基因簇中的rs17119975,rs651821,rs7396835和rs964184进行了基因分型。通过问卷调查获得有关睡眠持续时间的信息。总胆固醇的变化,甘油三酯,高密度脂蛋白胆固醇(HDL-c),低密度脂蛋白胆固醇(LDL-c),从基线到5年随访进行评估。
多变量调整后,我们发现rs651821和加权遗传风险评分(GRS)与甘油三酯升高显著相关,在睡眠持续时间类别中,与甘油三酯变化的遗传关联持续增强。rs651821每增加风险等位基因的甘油三酯变化差异为0.028(SE=0.017,p=0.112),0.051(SE=0.009,p<0.001),在睡眠持续时间≤7、>7-<9和≥9小时的个体中,和0.064(SE=0.016,p<0.001),分别(p相互作用=0.031)。GRS还显示出与甘油三酯变化的睡眠持续时间类别的显著相互作用(p相互作用=0.010)。此外,4个SNPs和GRS均与HDL-c变化呈负相关.
睡眠时间延长可能会加剧APOA4-APOA5-ZPR1-BUD13基因簇SNPs对5年甘油三酯变化的不利影响。
Lipid profiles are influenced by both genetic and environmental factors. Genetic variants in the APOA4-APOA5-ZPR1-BUD13 gene cluster and aberrant sleep duration were independently identified to be associated with lipids in previous studies. We aimed to investigate whether sleep duration modified the genetic associations with longitudinal lipids changes.
Four single nucleotide polymorphisms (SNPs), rs17119975, rs651821, rs7396835, and rs964184 in the APOA4-APOA5-ZPR1-BUD13 gene cluster were genotyped among 8648 apparently healthy subjects from the Dongfeng-Tongji (DFTJ) cohort. Information on sleep duration was obtained by questionnaires. Changes in total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), were evaluated from baseline to 5-year follow-up.
After multivariate adjustments, we found that rs651821 and weighted genetic risk score (GRS) were significantly associated with increased triglyceride, and the genetic association with triglyceride change consistently strengthened across sleep duration categories. The differences in triglyceride changes per increment of risk allele for rs651821 were 0.028 (SE = 0.017, p = 0.112), 0.051 (SE = 0.009, p < 0.001), and 0.064 (SE = 0.016, p < 0.001) in individuals with sleep duration ≤7, >7-<9, and ≥9 h, respectively (p interaction = 0.031). The GRS also showed a significant interaction with sleep duration categories for triglyceride change (p interaction = 0.010). In addition, all of the four SNPs and GRS were inversely related to HDL-c changes.
Longer sleep duration might exacerbate the adverse effects of SNPs in APOA4-APOA5-ZPR1-BUD13 gene cluster on 5-year triglyceride changes.