A Dopamine Receptor (DRD2) but Not Dopamine Transporter (DAT1) Gene Polymorphism is Associated with Neurocognitive Development of Mexican Preschool Children with Lead Exposure

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• 作者：Katarzyna Kordas ; PhD^a ; ^{kxk48@psu.edu} ; Adrienne S. Ettinger ; ScD^b ; David C. Bellinger ; PhD^b ; ^c ; Lourdes Schnaas ; MS^d ; Martha Marí ; a Té ; llez Rojo ; PhD^e ; Mauricio Herná ; ndez-Avila ; MD ; ScD^f ; Howard Hu ; MD ; ScD^g ; Robert O. Wright ; MD^b ; ^h
• 关键词：BLL ; Blood lead concentration ; DAT1 ; Dopamine transporter ; DRD2 ; Dopamine receptor-2 ; GCI ; General Cognitive Index ; MDI ; Mental Development Index ; PDI ; Psychomotor Development Index ; VNTR ; Variable number tandem repeat
• 刊名：The Journal of Pediatrics
• 出版年：2011
• 出版时间：October, 2011
• 年：2011
• 卷：159
• 期：4
• 页码：638-643
• 全文大小：133 K

文摘

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Objective

To investigate the effects of prenatal and postnatal lead exposure and polymorphisms in dopamine metabolism genes on neurocognitive development of Mexican children at 24 months (n = 220) and 48 months (n?= 186) of age.

Study design

We genotyped the dopamine transporter gene (DAT1; SLC6A3) variable nucleotide tandem repeat and the dopamine receptor D2 (DRD2) Taq1A single nucleotide polymorphism. Children were assessed at 24 months with Bayley Scales of Infant Development (Mental Development Index and Psychomotor Development Index) and at 48 months with McCarthy Scales of Children¡¯s Abilities.

Results

Blood lead concentration (BLL) in umbilical cord was 6.6 ¡À 3.3 ¦Ìg/dL (measured in 1995-96), 8.1 ¡À 4.4 ¦Ìg/dL at 24 months, and 8.1 ¡À 3.6 ¦Ìg/dL at 48 months. Cord BLL was negatively associated with Mental Development Index (P < .01) and Psychomotor Development Index (P < .1), but not McCarthy scores. The 48-month BLL, but not the 24-month BLL, was negatively associated with children¡¯s scores. Children with DRD2 TT genotype (variant) scored higher than children with CC genotype (wild type) on the Mental Development Index and McCarthy memory scale. Neither polymorphism modified the relationship between BLL (either prenatal or postnatal) and neurocognitive development.

Conclusion

Lead exposure was adversely associated with neurocognitive measures, whereas the DRD2 Taq1A TT variant was positively associated with neurocognitive measures. We found no evidence of gene-environment interactions on developmental outcomes in early childhood.