Use of Generalized Additive Model to Detect the Threshold of δ-Aminolevulinic Acid Dehydratase Activity Reduced by Lead Exposure.
ALAD polymorphism
blood lead
delta-aminolevulinic dehydratase (ALAD)
generalized additive model (GAM)
hemopoietic enzyme
Journal
International journal of environmental research and public health
ISSN: 1660-4601
Titre abrégé: Int J Environ Res Public Health
Pays: Switzerland
ID NLM: 101238455
Informations de publication
Date de publication:
07 08 2020
07 08 2020
Historique:
received:
28
06
2020
revised:
01
08
2020
accepted:
05
08
2020
entrez:
14
8
2020
pubmed:
14
8
2020
medline:
24
11
2020
Statut:
epublish
Résumé
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. 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. 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, 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.
Sections du résumé
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,
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.
Identifiants
pubmed: 32784669
pii: ijerph17165712
doi: 10.3390/ijerph17165712
pmc: PMC7460038
pii:
doi:
Substances chimiques
Biomarkers
0
Lead
2P299V784P
Porphobilinogen Synthase
EC 4.2.1.24
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Références
Indian J Clin Biochem. 2020 Jan;35(1):80-87
pubmed: 32071499
Clin Chem. 1985 Apr;31(4):601-5
pubmed: 3978795
Int Arch Occup Environ Health. 2004 Aug;77(6):395-400
pubmed: 15258767
Int Arch Occup Environ Health. 1996;68(2):126-32
pubmed: 8720283
J Pediatr. 1986 Jul;109(1):60-4
pubmed: 3723241
Environ Health Perspect. 1994 Sep;102 Suppl 3:215-9
pubmed: 7843101
Neurotoxicology. 2004 Dec;25(6):1041-7
pubmed: 15474621
Biol Trace Elem Res. 1991 Mar;28(3):223-31
pubmed: 1713045
Environ Health Perspect. 2001 Aug;109(8):827-32
pubmed: 11564619
Arch Environ Health. 1976 Jul-Aug;31(4):211-5
pubmed: 942263
J Occup Health. 2003 Jul;45(4):209-14
pubmed: 14646278
Occup Environ Med. 2000 Sep;57(9):588-94
pubmed: 10935939
Int J Environ Res Public Health. 2012 Jul;9(7):2326-38
pubmed: 22851944
Indian J Clin Biochem. 2012 Jan;27(1):83-9
pubmed: 23277717
Int Arch Occup Environ Health. 1977 Aug 31;39(3):135-41
pubmed: 924684
Toxicol Lett. 2018 Oct 1;295:351-356
pubmed: 30025905
Environ Health Perspect. 2003 Mar;111(3):335-41
pubmed: 12611663
Clin Chem. 1987 Oct;33(10):1807-10
pubmed: 3665033
J Occup Environ Med. 2000 Feb;42(2):151-5
pubmed: 10693075
Kaohsiung J Med Sci. 2002 Jul;18(7):347-54
pubmed: 12380325
Trends Biochem Sci. 1998 Jun;23(6):217-21
pubmed: 9644976
Toxicology. 1999 Jun 15;134(2-3):143-52
pubmed: 10403633
Am J Ind Med. 1999 Jun;35(6):595-603
pubmed: 10332513
Int J Environ Res Public Health. 2017 Apr 18;14(4):
pubmed: 28420209
Z Klin Chem Klin Biochem. 1974 Aug;12(8):389-90
pubmed: 4428852
Scand J Work Environ Health. 1975 Dec;1(4):219-32
pubmed: 1228901
Environ Sci Pollut Res Int. 2016 Jan;23(1):898-907
pubmed: 26351197
Environ Health Perspect. 2005 Oct;113(10):1313-7
pubmed: 16203232