氨基酸水平在多环芳烃暴露与代谢综合征关联中的效应修饰作用:一项焦化工人的巢式病例对照研究

Effect modification of amino acid levels in association between polycyclic aromatic hydrocarbon exposure and metabolic syndrome: A nested case-control study among coking workers

  • 摘要:
    背景 多环芳烃(PAHs)暴露与代谢综合征(MS)的发生有关,氨基酸在PAHs与MS关联中发挥的作用尚不清楚。
    目的 探讨焦化工人暴露于PAHs与MS发生的关联,以及氨基酸水平对这一关系的修饰作用。
    方法 本研究是一项非匹配巢式病例对照研究,分别于2017和2019年对太原两焦化厂工人进行了基线调查,并进行了为期4年的随访。该队列包括667名焦化工人。选取随访中84名新发病例作为病例组,278人为对照组,共362人纳入研究。使用超高效液相色谱-质谱联用技术(UPLC-MS/MS)检测工人尿中的11种PAHs代谢物和17种血浆氨基酸。使用logistic回归估计单种PAHs代谢物与MS之间的关联。按氨基酸浓度的中位数分层,使用贝叶斯核机器回归(BKMR)模型评估PAHs暴露对MS的混合暴露效应。因数据分布呈偏态,分析中所有的PAHs代谢物和氨基酸的值都经过自然对数ln转换(以lnv表示)。
    结果 362名参与者的年龄中位数为37岁,其中男性占83.2%。与对照组相比,病例组工人尿中2-羟基菲(2-OHPhe)、9-羟基菲(9-OHPhe)、羟基菲(OHPhe)浓度更高(P=0.005,P=0.049,P=0.004);血浆中支链氨基酸(BCAA)和芳香族氨基酸(AAA)浓度更高(P<0.05)。在调整混杂因素后,研究对象尿中lnv2-OHPhe每增加一个单位,发生MS的OR及其95%CI达1.57(1.11~2.26);lnvOHPhe每增加一个单位,发生MS的OR及其95%CI达1.82(1.16~2.90)。酪氨酸、亮氨酸、AAA与MS之间的非线性关联有统计学意义;酪氨酸、亮氨酸和AAA在低水平时,并不会增加MS的发病风险;而在高水平时,会导致MS的发病风险升高。在低水平氨基酸组、低水平BCAA组和低水平AAA组中均发现,与PAHs代谢物水平处于P50相比,PAHs代谢物水平处于P75时发生MS的OR及其95%CI的对数值分别为0.158(0.150~0.166)、0.218(0.209~0.227)和0.262(0.241~0.282);但在高水平氨基酸组中未见PAHs与MS的关联。
    结论 氨基酸在PAHs与MS的关联中起效应修饰作用,在血浆氨基酸水平低的人群中发现,MS的发病风险随着PAHs混合暴露浓度上升而升高;并且这一效应可能是低水平BCAA和AAA所引起。

     

    Abstract:
    Background Exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with the development of metabolic syndrome (MS). However, the role of amino acids in PAH-induced MS remains unclear.
    Objective To explore the impact of PAHs exposure on the incidence of MS among coking workers, and to determine potential modifying effect of amino acid on this relationship.
    Methods Unmatched nested case-control design was adopted and the baseline surveys of coking workers were conducted in two plants in Taiyuan in 2017 and 2019, followed by a 4-year follow-up. The cohort comprised 667 coking workers. A total of 362 participants were included in the study, with 84 newly diagnosed cases of MS identified as the case group and 278 as the control group. Urinary levels of 11 PAH metabolites and plasma levels of 17 amino acids were measured by ultrasensitive performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Logistic regression was used to estimate the association between individual PAH metabolites and MS. Stratified by the median concentration of amino acids, Bayesian kernel machine regression (BKMR) model was employed to assess the mixed effects of PAHs on MS. Due to the skewed data distribution, all PAH metabolites and amino acids in the analysis were converted by natural logarithm ln (expressed as lnv).
    Results The median age of the 362 participants was 37 years, and 83.2% were male. Compared to the control group, the case group exhibited higher concentrations of urinary 2-hydroxyphenanthrene (2-OHPhe), 9-hydroxyphenanthrene (9-OHPhe), and hydroxyphenanthrene (OHPhe) (P=0.005, P=0.049, and P=0.004, respectively), as well as elevated levels of plasma branched chain amino acid (BCAA) and aromatic amino acid (AAA) (P<0.05). After being adjusted for confounding factors, for every unit increase in lnv2-OHPhe in urine, the OR (95%CI) of MS was 1.57 (1.11, 2.26), and for every unit increase in lnvOHPhe, the OR (95%CI) of MS was 1.82 (1.16, 2.90). Tyrosine, leucine, and AAA all presented a significant nonlinear correlation with MS. At low levels, tyrosine, leucine, and AAA did not significantly increase the risk of MS, but at high levels, they increased the risk of MS. In the low amino acid concentration group, as well as in the low BCAA and low AAA concentration groups, it was found that compared to the PAH metabolite levels at the 50th percentile (P50), the log-odds of MS when the PAH metabolite levels was at the 75th percentile (P75) were 0.158 (95%CI: 0.150, 0.166), 0.218 (95%CI: 0.209, 0.227), and 0.262 (95% CI: 0.241, 0.282), respectively, However, no correlation between PAHs and MS was found in the high amino acid concentration group.
    Conclusion Amino acids modify the effect of PAHs exposure on the incidence of MS. In individuals with low plasma amino acid levels, the risk of developing MS increases with higher concentrations of mixed PAH exposure. This effect is partly due to the low concentrations of BCAA and AAA.

     

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