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Modification by the genes ALAD and VDR of lead-induced cognitive effects in children.
Neurotoxicology. 2012 Jan; 33(1):37-43.N

Abstract

Lead has negative effect on cognitive functions in children. However, individuals differ in susceptibility. One possible explanation is a genetic predisposition. Polymorphisms in the δ-aminolevulinic acid dehydratase (ALAD) and the vitamin D receptor (VDR) genes may modify lead metabolism and neurotoxicity, but information regarding the central nervous system is very limited. The aim of the study was to determine whether ALAD and VDR polymorphisms modify blood lead (B-Pb), and the association between B-Pb and cognitive function (IQ) in children. In 2007-2010 a cohort of 175 children (age 6-10years, mean 7.8) was recruited in Southern Poland, tested for IQ (Wechsler intelligence scale) and analyzed for B-Pb (range 9.0-221; mean 46.6μg/L), ALAD (RsaI, MspI) and VDR (FokI, BsmI, TaqI) polymorphisms. ALAD or VDR genotypes were not associated with B-Pb. B-Pb was non-significantly negatively associated with full scale IQ (r(S)=-0.11; P=0.14), and significantly with performance subscale results (r(S)=-0.19; P=0.01). The ALAD RsaI polymorphism modified the relationship between full scale IQ and B-Pb: RsaI T carriers had a steeper slope compared to CC homozygote carriers (β coefficient -0.06 vs 0.32, respectively, P for interaction <0.001, adjusted for the child's age, mother's education and family income). This means that with increasing B-Pb with 1μg/L, T carriers demonstrate 0.06 score lower IQ. For the VDR BsmI, B carriers had a steeper slope than the bb homozygotes carriers (β coefficient -0.08 vs 0.16, respectively, P for interaction=0.001), and similar effect was found for TaqI t carriers vs TT homozygotes (P for interaction=0.02). For ALAD MspI and VDR FokI there was no significant modification. The ALAD RsaI, VDR BsmI and TaqI polymorphisms modified the relationship between IQ and B-Pb. Hence, there is a fraction of the population, which is particularly sensitive to lead neurotoxicity.

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Authors+Show Affiliations

Pawlas N
Institute of Occupational Medicine and Environmental Health, 13, Kościelna str., PL 41-200 Sosnowiec, Poland. n-pawlas@wp.pl
Broberg K
No affiliation info available
Olewińska E
No affiliation info available
Prokopowicz A
No affiliation info available
Skerfving S
No affiliation info available
Pawlas K
No affiliation info available

MeSH

AdolescentChildCohort StudiesFemaleGene Expression RegulationGenetic Predisposition to DiseaseHumansIntelligenceIntelligence TestsLeadLead PoisoningMaleMultivariate AnalysisNeuropsychological TestsPolandPolymorphism, GeneticPorphobilinogen SynthaseReceptors, CalcitriolRetrospective Studies

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22101007

Citation

Pawlas, Natalia, et al. "Modification By the Genes ALAD and VDR of Lead-induced Cognitive Effects in Children." Neurotoxicology, vol. 33, no. 1, 2012, pp. 37-43.
Pawlas N, Broberg K, Olewińska E, et al. Modification by the genes ALAD and VDR of lead-induced cognitive effects in children. Neurotoxicology. 2012;33(1):37-43.
Pawlas, N., Broberg, K., Olewińska, E., Prokopowicz, A., Skerfving, S., & Pawlas, K. (2012). Modification by the genes ALAD and VDR of lead-induced cognitive effects in children. Neurotoxicology, 33(1), 37-43. https://doi.org/10.1016/j.neuro.2011.10.012
Pawlas N, et al. Modification By the Genes ALAD and VDR of Lead-induced Cognitive Effects in Children. Neurotoxicology. 2012;33(1):37-43. PubMed PMID: 22101007.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Modification by the genes ALAD and VDR of lead-induced cognitive effects in children. AU - Pawlas,Natalia, AU - Broberg,Karin, AU - Olewińska,Elżbieta, AU - Prokopowicz,Adam, AU - Skerfving,Staffan, AU - Pawlas,Krystyna, Y1 - 2011/11/09/ PY - 2011/07/11/received PY - 2011/10/30/revised PY - 2011/10/30/accepted PY - 2011/11/22/entrez PY - 2011/11/22/pubmed PY - 2012/6/5/medline SP - 37 EP - 43 JF - Neurotoxicology JO - Neurotoxicology VL - 33 IS - 1 N2 - Lead has negative effect on cognitive functions in children. However, individuals differ in susceptibility. One possible explanation is a genetic predisposition. Polymorphisms in the δ-aminolevulinic acid dehydratase (ALAD) and the vitamin D receptor (VDR) genes may modify lead metabolism and neurotoxicity, but information regarding the central nervous system is very limited. The aim of the study was to determine whether ALAD and VDR polymorphisms modify blood lead (B-Pb), and the association between B-Pb and cognitive function (IQ) in children. In 2007-2010 a cohort of 175 children (age 6-10years, mean 7.8) was recruited in Southern Poland, tested for IQ (Wechsler intelligence scale) and analyzed for B-Pb (range 9.0-221; mean 46.6μg/L), ALAD (RsaI, MspI) and VDR (FokI, BsmI, TaqI) polymorphisms. ALAD or VDR genotypes were not associated with B-Pb. B-Pb was non-significantly negatively associated with full scale IQ (r(S)=-0.11; P=0.14), and significantly with performance subscale results (r(S)=-0.19; P=0.01). The ALAD RsaI polymorphism modified the relationship between full scale IQ and B-Pb: RsaI T carriers had a steeper slope compared to CC homozygote carriers (β coefficient -0.06 vs 0.32, respectively, P for interaction <0.001, adjusted for the child's age, mother's education and family income). This means that with increasing B-Pb with 1μg/L, T carriers demonstrate 0.06 score lower IQ. For the VDR BsmI, B carriers had a steeper slope than the bb homozygotes carriers (β coefficient -0.08 vs 0.16, respectively, P for interaction=0.001), and similar effect was found for TaqI t carriers vs TT homozygotes (P for interaction=0.02). For ALAD MspI and VDR FokI there was no significant modification. The ALAD RsaI, VDR BsmI and TaqI polymorphisms modified the relationship between IQ and B-Pb. Hence, there is a fraction of the population, which is particularly sensitive to lead neurotoxicity. SN - 1872-9711 UR - https://www.unboundmedicine.com/medline/citation/22101007/Modification_by_the_genes_ALAD_and_VDR_of_lead_induced_cognitive_effects_in_children_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0161-813X(11)00200-2 DB - PRIME DP - Unbound Medicine ER -