| 1. |
- Pawlas, Natalia, et al.
(författare)
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Genetic modification of ALAD and VDR on lead-induced impairment of hearing in children.
- 2015
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Ingår i: Environmental Toxicology and Pharmacology. - : Elsevier BV. - 1872-7077 .- 1382-6689. ; 39:3, s. 1091-1098
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Tidskriftsartikel (refereegranskat)abstract
- Polymorphisms in the δ-aminolevulinic acid dehydratase (ALAD) and the vitamin D receptor (VDR) genes may modify lead metabolism and neurotoxicity. Two cohorts of children were examined for hearing [pure-tone audiometry (PTA), brain stem auditory evoked potentials (BAEP)], acoustic otoemission (transient emission evoked by a click) and blood-lead concentrations (B-Pb). The children were genotyped for polymorphisms in ALAD and VDR. The median B-Pbs were 55 and 36μg/L in the two cohorts (merged cohort 45μg/L). B-Pb was significantly associated with impaired hearing when tested with PTA (correlation coefficient rS=0.12; P<0.01), BAEP (rS=0.18; P<0.001) and otoemission (rS=-0.24; P<0.001). VDR significantly modified the lead-induced effects on PTA. Carriers of the VDR alleles BsmI B, VDR TaqI t and VDR FokI F showed greater toxic effects on PTA, compared to BsmI bb, VDR TaqI TT and VDR FokI ff carriers. No significant interaction was found for ALAD. Lead impairs hearing functions in the route from the cochlea to the brain stem at low-level exposure, and polymorphisms in VDR significantly modify these effects.
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| 2. |
- Pawlas, Natalia, et al.
(författare)
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Modification by the genes ALAD and VDR of lead-induced cognitive effects in children
- 2012
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Ingår i: NeuroToxicology. - : Elsevier BV. - 1872-9711 .- 0161-813X. ; 33:1, s. 37-43
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Tidskriftsartikel (refereegranskat)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 B-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 6-10 years, mean 7.8) was recruited in Southern Poland, tested for IQ (Wechsler intelligence scale) and analyzed for B-Pb (range 9.0-221; mean 46.6 mu g/L), ALAD (Rsal, Mspl) and VDR (Fokl, Bsml, Taql) 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 Rsal polymorphism modified the relationship between full scale IQ and B-Pb: Rsal T carriers had a steeper slope compared to CC homozygote carriers (beta 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 1 mu g/L,T carriers demonstrate 0.06 score lower IQ. For the VDR Bsml, B carriers had a steeper slope than the bb homozygotes carriers (beta coefficient -0.08 vs 0.16, respectively, P for interaction = 0.001), and similar effect was found for Taql t carriers vs TT homozygotes (P for interaction = 0.02). For ALAD Mspl and VDR Fokl there was no significant modification. The ALAD Rsal, VDR Bsml and Taql polymorphisms modified the relationship between IQ and B-Pb. Hence, there is a fraction of the population, which is particularly sensitive to lead neurotoxicity. (C) 2011 Elsevier Inc. All rights reserved.
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