title: Genetic modification of ALAD and VDR on lead-induced impairment of hearing in children.
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.
authors.affiliation: Institute of Occupational Medicine and Environmental Health, PL 41-200 Sosnowiec, Poland. Electronic address: n-pawlas@wp.pl.
authors.forename: Natalia
authors.initials: N
authors.lastname: Pawlas
authors.affiliation: Division of Occupational and Environmental Medicine, Lund University, SE-22185 Lund, Sweden; Unit of Metals and Health, Institute of Environmental Medicine, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Broberg
authors.affiliation: Institute of Occupational Medicine and Environmental Health, PL 41-200 Sosnowiec, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Olewińska
authors.affiliation: Institute of Occupational Medicine and Environmental Health, PL 41-200 Sosnowiec, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Kozłowska
authors.affiliation: Division of Occupational and Environmental Medicine, Lund University, SE-22185 Lund, Sweden.
authors.forename: Staffan
authors.initials: S
authors.lastname: Skerfving
authors.affiliation: Institute of Occupational Medicine and Environmental Health, PL 41-200 Sosnowiec, Poland; Department of Hygiene, Wroclaw Medical University, PL 50-368 Wrocław, Poland.
authors.forename: Krystyna
authors.initials: K
authors.lastname: Pawlas
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D016057:Evoked Potentials, Auditory, Brain Stem; D005260:Female; D034381:Hearing Loss / Q000097:blood / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D006320:Hearing Tests; D006801:Humans; D007854:Lead / Q000097:blood* / Q000633:toxicity; D008297:Male; D011110:Polymorphism, Genetic; D000623:Porphobilinogen Synthase / Q000235:genetics*; D018167:Receptors, Calcitriol / Q000235:genetics*
chemical_list: D018167:Receptors, Calcitriol; C579457:VDR protein, human; D007854:Lead; D000623:Porphobilinogen Synthase
keywords: ALAD polymorphism; Brainstem auditory evoked potential; Gene–environment interaction; Lead; Neurotoxicity; Otoemission; Pure-tone audiometry; VDR polymorphism; rs1139488; rs1544410; rs1800435; rs2228570; rs731236