Associations of Perfluoroalkyl substances with blood lipids and Apolipoproteins in lipoprotein subspecies: the POUNDS-lost study
Associations of Perfluoroalkyl substances with blood lipids and Apolipoproteins in lipoprotein subspecies: the POUNDS-lost study
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脂蛋白亚种中全氟烷基物质与血脂和载脂蛋白的关系：POUNDS丢失研究
DOI：
10.1186/s12940-020-0561-8
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发表时间：
2020-01-13
影响因子：
6
通讯作者：
Sun, Qi
中科院分区：
文献类型：
--
作者：
Liu, Gang;Zhang, Bo;Sun, Qi
背景全氟烷基物质（PFAS）暴露与血脂和脂蛋白的关系是不一致的，现有的研究没有考虑脂蛋白亚种的代谢异质性。本研究旨在探讨血浆PFAS浓度与脂蛋白和载脂蛋白亚种之间的关系。方法：研究对象为326名男性和女性，来自为期2年的新型饮食策略预防肥胖（POUNDS）减肥随机试验。在基线时测定血浆中全氟辛烷磺酸（PFOS）、全氟辛酸（PFOA）、全氟己磺酸（PFHxS）、全氟壬酸（PFNA）和全氟癸酸（PFDA） 5种全氟磺酸。对于脂蛋白和载脂蛋白亚种，总血浆首先按载脂蛋白C-III含量进行分级，然后按密度进行分级。然后在基线和2年后测量每个亚组的载脂蛋白ob、apoC-III和载脂蛋白e浓度，以及甘油三酯和胆固醇含量。结果对于基线时总血浆中的脂质和载脂蛋白，升高的血浆PFAS浓度与较高的载脂蛋白ob和apoC-III浓度显著相关，但与总胆固醇或甘油三酯无关。在对生活方式因素、降脂药物使用和饮食干预组进行多因素调整后，PFAS浓度主要与含有apoC-III的中低密度脂蛋白（IDL + LDL）和高密度脂蛋白（HDL）中的脂质或载脂蛋白浓度相关。比较PFOA的最高和最低三分位数，apoB的最小二乘平均值（SE） （mg/dl）为4.16（0.4）比3.47 (0.4)(P趋势= 0.04)，apoC-III的最小二乘平均值（SE）为2.03（0.2）比1.66 (0.2)(P趋势= 0.04)，含有apoC-III的IDL + LDL分数中甘油三酯的最小二乘平均值（SE）为8.4（0.8）比6.8 (0.8)（P趋势= 0.03）。对于含有apoC-III的HDL，比较PFOA的最高和最低分位数，apoC-III的最小二乘平均值（SE） （mg/dl）分别为11.9（0.7）和10.4 (0.7)（P趋势= 0.01）。此外，PFNA和PFDA浓度升高也与含有apoC-III的HDL中apoE浓度升高显著相关（P趋势< 0.01）。在基线PFAS浓度和2年测量的脂蛋白亚种之间也存在类似的关联模式。在干预期间，基线PFAS水平与脂蛋白亚种的变化无关。结论：我们的研究结果表明，血浆PFAS浓度主要与含有apoC-III的IDL、LDL和HDL亚种的血脂和载脂蛋白相关，这与流行病学研究中心血管风险升高有关。未来对pfas相关心血管风险的研究应集中在脂质亚组分上。
Background The associations of perfluoroalkyl substance (PFAS) exposure with blood lipids and lipoproteins are inconsistent, and existing studies did not account for metabolic heterogeneity of lipoprotein subspecies. This study aimed to examine the associations between plasma PFAS concentrations and lipoprotein and apolipoprotein subspecies. Methods The study included 326 men and women from the 2-year Prevention of Obesity Using Novel Dietary Strategies (POUNDS) Lost randomized trial. Five PFASs, including perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexanesulfonic acid (PFHxS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA), were measured in plasma at baseline. For lipoprotein and apolipoprotein subspecies, total plasma was fractionated first by apolipoprotein (apo) C-III content and then by density. Each subfraction was then measured for apoB, apoC-III, and apoE concentrations, as well as triglyceride and cholesterol contents, both at baseline and at 2 years. Results For lipids and apolipoproteins in total plasma at baseline, elevated plasma PFAS concentrations were significantly associated with higher apoB and apoC-III concentrations, but not with total cholesterol or triglycerides. After multivariate adjustment of lifestyle factors, lipid-lowering medication use, and dietary intervention groups, PFAS concentrations were primarily associated with lipids or apolipoprotein concentrations in intermediate-to-low density lipoprotein (IDL + LDL) and high-density lipoprotein (HDL) that contain apoC-III. Comparing the highest and lowest tertiles of PFOA, the least-square means (SE) (mg/dl) were 4.16 (0.4) vs 3.47 (0.4) for apoB (P trend = 0.04), 2.03 (0.2) vs 1.66 (0.2) for apoC-III (P trend = 0.04), and 8.4 (0.8) vs 6.8 (0.8) for triglycerides (P trend = 0.03) in IDL + LDL fraction that contains apoC-III. For HDL that contains apoC-III, comparing the highest and lowest tertiles of PFOA, the least-square means (SE) (mg/dl) of apoC-III were 11.9 (0.7) vs 10.4 (0.7) (P trend = 0.01). In addition, elevated PFNA and PFDA concentrations were also significantly associated with higher concentrations of apoE in HDL that contains apoC-III (P trend< 0.01). Similar patterns of associations were demonstrated between baseline PFAS concentrations and lipoprotein subspecies measured at 2 years. Baseline PFAS levels were not associated with changes in lipoprotein subspecies during the intervention. Conclusions Our results suggest that plasma PFAS concentrations are primarily associated with blood lipids and apolipoproteins in subspecies of IDL, LDL, and HDL that contain apoC-III, which are associated with elevated cardiovascular risk in epidemiological studies. Future studies of PFAS-associated cardiovascular risk should focus on lipid subfractions.