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应用广义加性模型探测铅暴露降低 δ-氨基酮戊酸脱水酶活性的阈值。

Use of Generalized Additive Model to Detect the Threshold of δ-Aminolevulinic Acid Dehydratase Activity Reduced by Lead Exposure.

机构信息

Department of Occupational and Environmental Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.

Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.

出版信息

Int J Environ Res Public Health. 2020 Aug 7;17(16):5712. doi: 10.3390/ijerph17165712.

DOI:10.3390/ijerph17165712
PMID:32784669
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7460038/
Abstract

BACKGROUND

Lead inhibits the enzymes in heme biosynthesis, mainly reducing δ-aminolevulinic acid dehydratase (ALAD) activity, which could be an available biomarker. The aim of this study was to detect the threshold of δ-aminolevulinic acid dehydratase activity reduced by lead exposure.

METHODS

We collected data on 121 lead workers and 117 non-exposed workers when annual health examinations were performed. ALAD activity was determined by the standardized method of the European Community. ALAD G177C (rs1800435) genotyping was conducted using the polymerase chain reaction and restricted fragment length polymorphism (PCR-RFLP) method. In order to find a threshold effect, we used generalized additive models (GAMs) and scatter plots with smoothing curves, in addition to multiple regression methods.

RESULTS

There were 229 ALAD1-1 homozygotes and 9 ALAD1-2 heterozygotes identified, and no ALAD2-2 homozygotes. Lead workers had significantly lower ALAD activity than non-exposed workers (41.6 ± 22.1 vs. 63.3 ± 14.0 U/L, < 0.001). The results of multiple regressions showed that the blood lead level (BLL) was an important factor inversely associated with ALAD activity. The possible threshold of BLL affecting ALAD activity was around 5 μg/dL.

CONCLUSIONS

ALAD activity was inhibited by blood lead at a possible threshold of 5 μg/dL, which suggests that ALAD activity could be used as an indicator for lead exposure regulation.

摘要

背景

铅会抑制血红素生物合成中的酶,主要是降低 δ-氨基酮戊酸脱水酶(ALAD)的活性,这可能是一种可用的生物标志物。本研究旨在检测铅暴露导致 δ-氨基酮戊酸脱水酶活性降低的阈值。

方法

我们收集了 121 名铅作业工人和 117 名非暴露工人在年度体检时的数据。ALAD 活性通过欧洲共同体的标准化方法测定。使用聚合酶链反应和限制性片段长度多态性(PCR-RFLP)方法进行 ALAD G177C(rs1800435)基因分型。为了找到阈值效应,我们使用了广义加性模型(GAMs)和带有平滑曲线的散点图,以及多元回归方法。

结果

共鉴定出 229 名 ALAD1-1 纯合子和 9 名 ALAD1-2 杂合子,没有 ALAD2-2 纯合子。铅作业工人的 ALAD 活性明显低于非暴露工人(41.6±22.1 与 63.3±14.0 U/L,<0.001)。多元回归的结果表明,血铅水平(BLL)是与 ALAD 活性呈负相关的重要因素。可能影响 ALAD 活性的 BLL 阈值约为 5μg/dL。

结论

血铅可能在 5μg/dL 的阈值下抑制 ALAD 活性,这表明 ALAD 活性可作为铅暴露调节的指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67c7/7460038/e5c9229070d5/ijerph-17-05712-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67c7/7460038/e5c9229070d5/ijerph-17-05712-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67c7/7460038/e5c9229070d5/ijerph-17-05712-g001.jpg

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