Genetic susceptibility to low-level lead exposure in men: Insights from ALAD polymorphisms.

Autor: Stajnko A; Department of Environmental Sciences, Jožef Stefan Institute, Jamova Cesta 39, 1000, Ljubljana, Slovenia. Electronic address: anja.stajnko@ijs.si., Palir N; Department of Environmental Sciences, Jožef Stefan Institute, Jamova Cesta 39, 1000, Ljubljana, Slovenia; Jožef Stefan International Postgraduate School, Jamova Cesta 39, 1000, Ljubljana, Slovenia., Snoj Tratnik J; Department of Environmental Sciences, Jožef Stefan Institute, Jamova Cesta 39, 1000, Ljubljana, Slovenia., Mazej D; Department of Environmental Sciences, Jožef Stefan Institute, Jamova Cesta 39, 1000, Ljubljana, Slovenia., Sešek Briški A; Institute of Clinical Chemistry and Biochemistry, University Medical Centre Ljubljana, Njegoševa 4, 1000, Ljubljana, Slovenia., Runkel AA; Department of Environmental Sciences, Jožef Stefan Institute, Jamova Cesta 39, 1000, Ljubljana, Slovenia., Horvat M; Department of Environmental Sciences, Jožef Stefan Institute, Jamova Cesta 39, 1000, Ljubljana, Slovenia; Jožef Stefan International Postgraduate School, Jamova Cesta 39, 1000, Ljubljana, Slovenia., Falnoga I; Department of Environmental Sciences, Jožef Stefan Institute, Jamova Cesta 39, 1000, Ljubljana, Slovenia.
Jazyk: angličtina
Zdroj: International journal of hygiene and environmental health [Int J Hyg Environ Health] 2024 Mar; Vol. 256, pp. 114315. Date of Electronic Publication: 2024 Jan 01.
DOI: 10.1016/j.ijheh.2023.114315
Abstrakt: The genetic susceptibility to low-level lead (Pb) exposure in general populations has been poorly investigated and is limited to the single nucleotide polymorphism (SNP) rs1800435 in the delta-aminolevulinic acid dehydratase gene (ALAD). This study explored associations between ten selected ALAD SNPs with Pb concentrations in blood (BPb) and urine (UPb) among 281 men aged 18-49 years from Slovenia, including 20 individuals residing in a Pb-contaminated area. The geometric mean (range) of BPb and UPb were 19.6 (3.86-84.7) μg/L and 0.69 (0.09-3.82) μg/L SG, respectively. The possible genetic influence was assessed by examining SNP haplotypes, individual SNPs, and the combination of two SNPs using multiple linear regression analyses. While no significant associations were found for haplotypes, the presence of variant alleles of rs1800435 and rs1805312 resulted in an 11% and 13% decrease in BPb, respectively, while the presence of variant allele of rs1139488 (homozygous only) exhibited significant 20% increase in BPb, respectively. Additionally, variant allele of rs1800435 resulted in lower UPb. Individual SNPs in the model explained only around 1 additional percentage point of BPb variability. In contrast, combination analyses identified six combinations of two SNPs, which significantly explained 3-22 additional percentage points of BPb variability, with the highest explanatory power observed for the rs1800435-rs1139488 and rs1139488-rs1805313 combinations. Moreover, excluding participants from the Pb-contaminated area indicated that exposure level influenced SNPs-Pb associations. Our results confirm the importance of the ALAD gene in Pb kinetics even at low exposure levels. Additionally, we demonstrated that identifying individuals with specific combinations of ALAD SNPs explained a larger part of Pb variability, suggesting that these combinations, pending confirmation in other populations and further evaluation through mechanistic studies, may serve as superior susceptibility biomarker in Pb exposure compared to individual SNPs.
Competing Interests: Declaration of competing interest The authors report no conflict of interest.
(Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)
Databáze: MEDLINE
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