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

Autor: Te-Yu Liu, Chao-Ling Wang, Chia-Yen Dai, Hung-Yi Chuang, Chen-Cheng Yang, Chan-Ching Huang
Rok vydání: 2020
Předmět:
Adult
Male
medicine.medical_specialty
blood lead
Genotype
European community
Health
Toxicology and Mutagenesis
lcsh:Medicine
010501 environmental sciences
Polymerase Chain Reaction
01 natural sciences
Article
03 medical and health sciences
hemopoietic enzyme
Risk Factors
Occupational Exposure
Internal medicine
Threshold effect
medicine
Humans
ALAD polymorphism
030304 developmental biology
0105 earth and related environmental sciences
generalized additive model (GAM)
0303 health sciences
medicine.diagnostic_test
Chemistry
lcsh:R
Generalized additive model
Heme biosynthesis
Public Health
Environmental and Occupational Health
Porphobilinogen Synthase
δ-aminolevulinic acid
Porphyrias
Hepatic
Endocrinology
Lead
Dehydratase
Lead exposure
Blood lead level
delta-aminolevulinic dehydratase (ALAD)
Biomarkers
Polymorphism
Restriction Fragment Length
Zdroj: International Journal of Environmental Research and Public Health
Volume 17
Issue 16
International Journal of Environmental Research and Public Health, Vol 17, Iss 5712, p 5712 (2020)
ISSN: 1660-4601
DOI: 10.3390/ijerph17165712
Popis: Background: Lead inhibits the enzymes in heme biosynthesis, mainly reducing &delta
aminolevulinic acid dehydratase (ALAD) activity, which could be an available biomarker. The aim of this study was to detect the threshold of &delta
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 &mu
g/dL. Conclusions: ALAD activity was inhibited by blood lead at a possible threshold of 5 &mu
g/dL, which suggests that ALAD activity could be used as an indicator for lead exposure regulation.
Databáze: OpenAIRE
Externí odkaz: