基于路径的炎症基因评分：邻苯二甲酸盐诱发不良神经发育结果的易感性指标。

IF 4.5 2区医学 Q1 INFECTIOUS DISEASES

International journal of hygiene and environmental health Pub Date : 2024-12-24 DOI:10.1016/j.ijheh.2024.114514

Ahmed Elagali , Alex Eisner , Samuel Tanner , Katherine Drummond , Christos Symeonides , Chloe Love , Mimi LK. Tang , Toby Mansell , David Burgner , Fiona Collier , Peter D. Sly , Martin O'Hely , Sarah Dunlop , Peter Vuillermin , Anne-Louise Ponsonby

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引用次数: 0

摘要

简介：邻苯二甲酸盐是一种用于增强塑料制品柔韧性的化学添加剂，它很容易释放到环境中，并会通过炎症等多种机制损害大脑发育。影响个体炎症易感性的遗传变异可能在邻苯二甲酸盐暴露对神经发育的影响中发挥作用，但目前还没有针对炎症遗传易感性的总结性测量方法。方法：基于大脑和其他组织中炎症反应通路的转录活性，我们开发了炎症遗传通路功能评分（gPFSin）。利用Barwon婴儿研究（n = 1074的出生队列），我们研究了gPFSin与关键神经发育结局之间的联系，以及产前邻苯二甲酸盐水平、儿童对炎症的遗传易感（gPFSin）和不良神经发育结局之间的相互作用。结果：回归技术揭示了gpfsin -邻苯二甲酸盐组合与关键神经发育结局之间的一致关联。高gPFSin评分与11.5岁时医生诊断的自闭症谱系障碍（ASD）和注意力缺陷/多动障碍（ADHD）的风险增加相关，调整后的优势比分别为2.15（p = 0.039）和2.42（p = 0.005）。此外，高gPFSin和产前邻苯二甲酸盐暴露的个体表现出更多的神经发育问题。这包括高gPFSin和邻苯二甲酸双（2-乙基己基）酯（DEHP）水平与父母报告的ASD特征和医生诊断的ASD之间的关联。这种相互作用的归因比例分别为0.39 （p = 0.045）和0.37 （p = 0.037）。结论：这些发现为妊娠期邻苯二甲酸盐暴露和炎症与不良神经发育联系起来提供了证据，并强调了对炎症遗传易感性较高的儿童的风险增加。

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A pathway-based genetic score for inflammation: An indicator of vulnerability to phthalate-induced adverse neurodevelopment outcomes

Introduction

Phthalates, chemical additives used to enhance plastic products' flexibility, are easily released into the environment, and can harm the brain development through various mechanisms including inflammation. Genetic variation influencing an individual's susceptibility to inflammation may play a role in the effects of phthalate exposure on neurodevelopment however there is no summary measure developed for genetic susceptibility to inflammation.

Methods

We developed a genetic pathway function score for inflammation (gPFSⁱⁿ), based on the transcriptional activity of the inflammatory response pathway in the brain and other tissues. Using the Barwon Infant Study (a birth cohort of n = 1074), we examined the connection between gPFSⁱⁿ and key neurodevelopmental outcomes, along with the interplay between prenatal phthalate levels, children's genetic susceptibility to inflammation (gPFSⁱⁿ), and adverse neurodevelopmental outcomes.

Results

Regression techniques revealed consistent associations between gPFSⁱⁿ-phthalate combinations and key neurodevelopmental outcomes. A high gPFSⁱⁿ score was associated with an increased risk of doctor-diagnosed Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD) by age 11.5 years, with adjusted odds ratios of 2.15(p = 0.039) and 2.42(p = 0.005), respectively. Furthermore, individuals with both high gPFSⁱⁿ and prenatal phthalate exposure exhibited more neurodevelopmental problems. This included associations of high gPFSⁱⁿ and bis(2-ethylhexyl) phthalate (DEHP) levels with parent-reported ASD traits and doctor-diagnosed ASD. The attributable proportions due to this interaction were 0.39 (p = 0.045) and 0.37 (p = 0.037), respectively.

Conclusion

These findings contribute to the evidence linking gestational phthalate exposure and inflammation to adverse neurodevelopment and underscoring increased risks in children with higher genetic susceptibility to inflammation.

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来源期刊

International journal of hygiene and environmental health 医学-传染病学

CiteScore

11.50

自引率

5.00%

发文量

151

审稿时长

22 days

期刊介绍： The International Journal of Hygiene and Environmental Health serves as a multidisciplinary forum for original reports on exposure assessment and the reactions to and consequences of human exposure to the biological, chemical, and physical environment. Research reports, short communications, reviews, scientific comments, technical notes, and editorials will be peer-reviewed before acceptance for publication. Priority will be given to articles on epidemiological aspects of environmental toxicology, health risk assessments, susceptible (sub) populations, sanitation and clean water, human biomonitoring, environmental medicine, and public health aspects of exposure-related outcomes.