Modification by the genes ALAD and VDR of lead-induced cognitive effects in children

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.