title: Hemoglobin, lead exposure, and intelligence quotient: effect modification by the DRD2 Taq IA polymorphism.
abstract: BACKGROUND
  Anemia and lead exposure remain significant public health issues in many parts of the world, often occurring together. Animal studies suggest that the dopamine D2 receptor (DRD2) mediates the effects of both lead and iron on cognition and behavior.
  
  
  OBJECTIVE
  We tested the hypothesis that the DRD2 Taq IA polymorphism modifies the effects of lead and hemoglobin on intelligence quotient (IQ) among children.
  
  
  METHODS
  Blood lead and hemoglobin were assessed in 717 children 3-7 years of age attending 12 schools in Chennai, India. IQ was determined using the Binet-Kamat scales of intelligence. Genotyping for the DRD2 polymorphism was carried out using a MassARRAY iPLEX platform. Stratified analyses and interaction models, using generalized estimating equations (GEEs), were used to explore interactions between lead and hemoglobin, and DRD2 Taq IA categories [homozygous variant (A1) vs. presence of wild-type allele (A2)].
  
  
  RESULTS
  After we controlled for potential confounders, a one-unit increase in log blood lead was associated with a decrease of 9 IQ points [95% confidence interval (CI), -18.08 to -0.16] in the homozygous-variant children (n = 73) compared with a decrease of 4 IQ points (95% CI, -7.21 to -0.69) among those with the wild-type allele (n = 644). Higher hemoglobin levels were associated with higher IQ in the children who carried the wild-type allele DRD2, but in children homozygous for the variant allele, an increase of 1 g/dL hemoglobin was associated with a decrease in 1.82 points of IQ (95% CI, -5.28 to 1.64; interaction term p-value = 0.02).
  
  
  CONCLUSIONS
  The results of this study suggest that the DRD2 Taq IA polymorphism disrupts the protective effect of hemoglobin on cognition and may increase the susceptibility to the deficits in IQ due to lead exposure.
authors.affiliation: Environmental and Occupational Health Sciences Institute, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 08854, USA. aroykaushik@gmail.com
authors.forename: Ananya
authors.initials: A
authors.lastname: Roy
authors.forename: Howard
authors.initials: H
authors.lastname: Hu
authors.forename: David C
authors.initials: DC
authors.lastname: Bellinger
authors.forename: Bhramar
authors.initials: B
authors.lastname: Mukherjee
authors.forename: Rama
authors.initials: R
authors.lastname: Modali
authors.forename: Khaja
authors.initials: K
authors.lastname: Nasaruddin
authors.forename: Joel
authors.initials: J
authors.lastname: Schwartz
authors.forename: Robert O
authors.initials: RO
authors.lastname: Wright
authors.forename: Adrienne S
authors.initials: AS
authors.lastname: Ettinger
authors.forename: Kavitha
authors.initials: K
authors.lastname: Palaniapan
authors.forename: Kalpana
authors.initials: K
authors.lastname: Balakrishnan
mesh_terms: D018798:Anemia, Iron-Deficiency / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003071:Cognition / Q000187:drug effects*; D004781:Environmental Exposure / Q000706:statistics & numerical data; D004785:Environmental Pollutants / Q000097:blood* / Q000633:toxicity; D005260:Female; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D007194:India; D007361:Intelligence Tests; D007854:Lead / Q000097:blood* / Q000633:toxicity; D008297:Male; D020641:Polymorphism, Single Nucleotide; D017448:Receptors, Dopamine D2 / Q000235:genetics* / Q000378:metabolism
chemical_list: D004785:Environmental Pollutants; D006454:Hemoglobins; D017448:Receptors, Dopamine D2; D007854:Lead