Institute of Occupational Medicine and Environmental Health, PL 41-200 Sosnowiec, Poland.
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.
Environ Toxicol Pharmacol. 2015 May;39(3):1091-8. doi: 10.1016/j.etap.2015.03.008. Epub 2015 Mar 14.
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.
δ-氨基酮戊酸脱水酶（ALAD）和维生素 D 受体（VDR）基因的多态性可能会改变铅的代谢和神经毒性。我们检查了两组儿童的听力[纯音听阈（PTA）、脑干听觉诱发电位（BAEP）]、声导发射（由点击引起的瞬态发射）和血铅浓度（B-Pb）。对 ALAD 和 VDR 基因的多态性进行了基因分型。两组儿童的 B-Pb 中位数分别为 55 和 36μg/L（合并组为 45μg/L）。B-Pb 与 PTA（相关系数 rS=0.12；P<0.01）、BAEP（rS=0.18；P<0.001）和导发射（rS=-0.24；P<0.001）测试的听力受损显著相关。VDR 显著改变了铅对 PTA 的诱导作用。与 BsmI bb、VDR TaqI TT 和 VDR FokI ff 携带者相比，VDR 等位基因 BsmI B、VDR TaqI t 和 VDR FokI F 的携带者对 PTA 的毒性作用更大。未发现 ALAD 有显著的交互作用。在低水平暴露下，铅会损害耳蜗到脑干的听力功能，而 VDR 的多态性显著改变了这些影响。
