Interactive effects of a DRD4 polymorphism, lead, and sex on executive functions in children.

BACKGROUND Prior studies have examined independent effects of a dopamine receptor D4 polymorphism (DRD4-7) and lead exposure on executive functions but not their interaction or the role of sex as a modifier of their effects. METHODS Multivariable analyses were used to examine effects of DRD4-7 genotype, 60-month blood lead level, and sex on spatial working memory, rule learning and reversal, spatial span, and planning for 174 children. RESULTS DRD4-7 was associated with poorer spatial working memory, and increasing blood lead levels were associated with impaired rule learning and reversal, spatial span, and planning. Adverse effects of lead on planning and rule learning and reversal were seen primarily for boys. In addition, the effect of lead on rule learning and reversal was evident predominately for those lacking DRD4-7. CONCLUSIONS We observed independent effects of DRD4-7 and lead on various executive functions and modifications of lead effects by DRD4 genotype and sex.