三个队列研究中的极端代谢健康评分与炎症和胆固醇转运的血浆蛋白标志物有关。

IF 5.6 2区 医学 Q1 GERIATRICS & GERONTOLOGY
Daniele Bizzarri, Erik B van den Akker, Marcel J T Reinders, René Pool, Marian Beekman, Nico Lakenberg, Nicolas Drouin, Kelly E Stecker, Albert J R Heck, Edward F Knol, Jeannette M Vergeer, M Arfan Ikram, Mohsen Ghanbari, Alain J van Gool, Joris Deelen, Bbmri-Nl, Dorret I Boomsma, P Eline Slagboom
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引用次数: 0

摘要

代谢健康评分是中老年个体生理虚弱的一个指标。当前研究的目的是探索哪些分子途径与代谢健康评分共同变化。使用Luminex细胞因子测定和基于液相色谱-质谱的蛋白质组学,我们从莱顿长寿研究(LLS)和鹿特丹研究(RS)两个大人群队列中选择了100个极端评分个体,并从荷兰双胞胎登记册(NTR)中选择了不一致的同卵双胞胎,探索了与差异相关的血浆蛋白。此外,我们利用726对单卵双胞胎(MZ)和450对异卵双胞胎(DZ)估计了得分的遗传力。在对比LLS和RS的极端评分个体中,我们发现3种(15种)细胞因子(GDF15、IL6和MIG)和106种(289种)血浆蛋白存在显著差异。健康相关的高、差评分与42种炎症和免疫相关蛋白水平(CRP、LBP、HPT)升高和71种HDL重塑和胆固醇转运相关蛋白(如APOA1、APOA2、APOA4和TETN)水平降低相关。使用NTR双胞胎,我们随后发现代谢健康评分具有中等遗传性(h2 = 0.4)。在选择最大不一致的MZ双胞胎中,我们发现68种血清蛋白与代谢健康评分相关,这表明在LLS和RS中观察到的关联中只有一小部分可能由遗传影响来解释。综上所述,我们的研究揭示了代谢健康评分、血浆蛋白、细胞因子和遗传影响之间复杂的相互作用,为未来旨在优化这一死亡率风险指标的研究铺平了道路。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Extreme MetaboHealth scores in three cohort studies associate with plasma protein markers for inflammation and cholesterol transport.

The MetaboHealth score is an indicator of physiological frailty in middle aged and older individuals. The aim of the current study was to explore which molecular pathways co-vary with the MetaboHealth score. Using a Luminex cytokine assay and liquid chromatography-mass spectrometry-based proteomics we explored the plasma proteins associating with the difference in 100 extreme scoring individuals selected from two large population cohorts, the Leiden Longevity Study (LLS) and the Rotterdam Study (RS), and discordant monozygotic twin pairs from the Netherlands Twin Register (NTR). In addition, we estimated the heritability of the score using 726 monozygotic (MZ) and 450 dizygotic (DZ) twin pairs. In the contrasting extreme scoring individuals from LLS and RS, we uncovered significant differences in 3 (out of 15) cytokines (GDF15, IL6, and MIG), and 106 (out of 289) plasma proteins. The high, poor health related, score associated with 42 increased inflammatory and immune related protein levels (CRP, LBP, HPT) and lowered levels of 71 HDL remodeling and cholesterol transport related proteins (e.g. APOA1, APOA2, APOA4, and TETN). Using the NTR twins, we subsequently showed that the MetaboHealth score is moderately heritable (h2 = 0.4). In MZ twins selected for maximal discordance within a pair we found 68 serum proteins associated with the MetaboHealth score indicating that only a minor part of the associations observed in LLS and RS is likely explained by genetic influences. Taken together, our study sheds light on the intricate interplay between the MetaboHealth score, plasma proteins, cytokines, and genetic influences, paving the way for future investigations aimed at optimizing this mortality risk indicator.

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来源期刊
Immunity & Ageing
Immunity & Ageing GERIATRICS & GERONTOLOGY-IMMUNOLOGY
CiteScore
10.20
自引率
3.80%
发文量
55
期刊介绍: Immunity & Ageing is a specialist open access journal that was first published in 2004. The journal focuses on the impact of ageing on immune systems, the influence of aged immune systems on organismal well-being and longevity, age-associated diseases with immune etiology, and potential immune interventions to increase health span. All articles published in Immunity & Ageing are indexed in the following databases: Biological Abstracts, BIOSIS, CAS, Citebase, DOAJ, Embase, Google Scholar, Journal Citation Reports/Science Edition, OAIster, PubMed, PubMed Central, Science Citation Index Expanded, SCImago, Scopus, SOCOLAR, and Zetoc.
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