title: Disturbance of posture in children with very low lead exposure, and modification by VDR FokI genotype.
abstract: OBJECTIVE
  Lead has a negative effect on the central nervous system (CNS), inter alia indicated by disturbance of posture. However, knowledge of the CNS effects at low exposure is insufficient. Individuals differ in vulnerability, possibly because of genetic predisposition. Polymorphisms in the δ-aminolevulinic acid dehydratase (ALAD) and vitamin D receptor (VDR) genes may modify lead metabolism and neurotoxicity. The objective of the study was to determine whether very low lead exposure affects posture in children, and whether ALAD and VDR genotypes modify the effect.
  
  
  METHODS
  In 1996-2001, 108 (age 5-13, mean 6.9), and in 2008-2010 231 (age 5-11, mean 7.9) children from Poland were tested by posturography and blood-lead concentration (B-Pb; medians 50 and 36 µg/L, respectively). The children were genotyped for ALAD (RsaI, MspI) and VDR (FokI, BsmI, TaqI).
  
  
  RESULTS
  There were correlations between posture and B-Pb (sway area with closed eyes: rS=0.24, P<0.001; velocity: rS=0.21, P<0.001). Significant effects (adjusted for the potential confounders height and mother´s education) were present already at (ln-transformed) B-Pb<50 µg/L [β (regression coefficient) for sway area 0.025, p=0.001), and even stronger than at higher levels (β=0.006, p=0.06, respectively)]. The ff carriers in VDR FokI polymorphism were more susceptible to the effect of lead on the balance system, while other VDR or ALAD genotypes did not significantly modify the effect.
  
  
  CONCLUSIONS
  Effects on CNS, as reflected by disturbances of posture, were present at very low lead exposure (B-Pb<50 µg/L), and the effect was significantly greater at such low B-Pbs than at higher. VDR FokI significantly modified the effect.
authors.affiliation: Institute of Occupational Medicine and Environmental Health, Sosnowiec, Poland.
authors.forename: Natalia
authors.initials: N
authors.lastname: Pawlas
authors.affiliation: Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Broberg
authors.affiliation: Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund, Sweden.
authors.forename: Staffan
authors.initials: S
authors.lastname: Skerfving
authors.affiliation: Institute of Occupational Medicine and Environmental Health, Sosnowiec, Poland; Department of Hygiene, Wroclaw Medical University, Wroclaw, Poland.
authors.forename: Krystyna
authors.initials: K
authors.lastname: Pawlas
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D002658:Developmental Disabilities / Q000139:chemically induced* / Q000235:genetics*; D005260:Female; D059647:Gene-Environment Interaction; D005838:Genotype; D006801:Humans; D007854:Lead / Q000097:blood / Q000633:toxicity*; D008297:Male; D011044:Poland; D020641:Polymorphism, Single Nucleotide; D000623:Porphobilinogen Synthase / Q000235:genetics* / Q000378:metabolism; D011187:Posture; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000378:metabolism
chemical_list: D018167:Receptors, Calcitriol; C579457:VDR protein, human; D007854:Lead; D000623:Porphobilinogen Synthase