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

Chan-Ching Huang, Chen-Cheng Yang, Te-Yu Liu, Chia-Yen Dai, Chao-Ling Wang and Hung-Yi Chuang
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Chan-Ching Huang: Department of Occupational and Environmental Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
Chen-Cheng Yang: Department of Occupational and Environmental Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
Te-Yu Liu: Department of Public Health, and Research Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
Chia-Yen Dai: Department of Occupational and Environmental Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
Chao-Ling Wang: Department of Occupational and Environmental Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan
Hung-Yi Chuang: Department of Occupational and Environmental Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan

IJERPH, 2020, vol. 17, issue 16, 1-10

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, p < 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.

Keywords: generalized additive model (GAM); blood lead; delta-aminolevulinic dehydratase (ALAD); ALAD polymorphism; hemopoietic enzyme (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2020
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