Institute of Occupational Medicine and Environmental Health, 13, Kościelna str., PL 41-200 Sosnowiec, Poland.
Neurotoxicology. 2012 Jan;33(1):37-43. doi: 10.1016/j.neuro.2011.10.012. Epub 2011 Nov 9.
Lead has negative effect on cognitive functions in children. However, individuals differ in susceptibility. One possible explanation is a genetic predisposition. Polymorphisms in the δ-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 6-10years, mean 7.8) was recruited in Southern Poland, tested for IQ (Wechsler intelligence scale) and analyzed for B-Pb (range 9.0-221; mean 46.6μg/L), ALAD (RsaI, MspI) and VDR (FokI, BsmI, TaqI) 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 RsaI polymorphism modified the relationship between full scale IQ and B-Pb: RsaI T carriers had a steeper slope compared to CC homozygote carriers (β 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 1μg/L, T carriers demonstrate 0.06 score lower IQ. For the VDR BsmI, B carriers had a steeper slope than the bb homozygotes carriers (β coefficient -0.08 vs 0.16, respectively, P for interaction=0.001), and similar effect was found for TaqI t carriers vs TT homozygotes (P for interaction=0.02). For ALAD MspI and VDR FokI there was no significant modification. The ALAD RsaI, VDR BsmI and TaqI polymorphisms modified the relationship between IQ and B-Pb. Hence, there is a fraction of the population, which is particularly sensitive to lead neurotoxicity.
铅对儿童的认知功能有负面影响。然而，个体对铅的易感性存在差异。一种可能的解释是遗传易感性。δ-氨基乙酰丙酸脱水酶（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，但有关中枢神经系统的信息非常有限。本研究的目的是确定 ALAD 和 VDR 多态性是否会改变血铅（B-Pb），以及 B-Pb 与儿童认知功能（智商）之间的关系。2007-2010 年，在波兰南部招募了一组 175 名 6-10 岁（平均 7.8 岁）的儿童，对他们进行智商（韦氏智力测验）测试，并检测 B-Pb（范围 9.0-221；平均 46.6μg/L）、ALAD（RsaI、MspI）和 VDR（FokI、BsmI、TaqI）多态性。ALAD 或 VDR 基因型与 B-Pb 无关。B-Pb 与全量表智商呈非显著负相关（r(S)=-0.11；P=0.14），与表现分量表结果显著相关（r(S)=-0.19；P=0.01）。ALAD RsaI 多态性改变了全量表智商与 B-Pb 之间的关系：与 CC 纯合子携带者相比，RsaI T 携带者的斜率更陡（β系数分别为-0.06 和 0.32，交互作用 P<0.001，调整儿童年龄、母亲教育程度和家庭收入）。这意味着，随着 B-Pb 增加 1μg/L，T 携带者的智商下降 0.06 分。对于 VDR BsmI，B 携带者的斜率比 bb 纯合子携带者更陡（β系数分别为-0.08 和 0.16，交互作用 P=0.001），而 TaqI t 携带者与 TT 纯合子的相似效果（交互作用 P=0.02）。对于 ALAD MspI 和 VDR FokI，没有发现显著的修饰作用。ALAD RsaI、VDR BsmI 和 TaqI 多态性改变了智商与 B-Pb 之间的关系。因此，有一部分人群对铅的神经毒性特别敏感。
