CYP1A1 Ile462Val and GSTT1 modify the effect of cord blood cotinine on neurodevelopment at 2 years of age

Neurotoxicology. 2008 Sep;29(5):839-45. doi: 10.1016/j.neuro.2008.05.006. Epub 2008 Jun 3.


Maternal exposure to environmental tobacco smoke (ETS) has been reported to be associated with children's neurobehavioral development but there was no studies investigating the genetic susceptibilities to maternal ETS exposure on children's neurodevelopment. The aim of the study was to explore the modification effect of metabolic gene polymorphisms to cord blood cotinine on children's neurodevelopment at the 2 years of age. This study is one investigation of the Taiwan Birth Panel Study and a total of 145 pregnant women and their neonates were recruited between April 2004 and January 2005. We interviewed them by a structured questionnaire after delivery and collected umbilical cord blood at birth. Cotinine in umbilical cord blood as an indicator of environmental tobacco smoke was analyzed by using HPLC-MS/MS and the detection limited of this method was 0.05ng/mL. Four metabolic genes, CYP1A1 MspI, CYP1A1 Ile462Val, GSTT1 and GSTM1 were identified. The Comprehensive Developmental Inventory for Infants and Toddlers (CDIIT) was used for assessing children's neurodevelopment at the 2 years of age accompanying with the measurement of Home Observation for Measurement of the Environment scale. We used multiple linear regression models to estimate the effects of cord blood cotinine and gene modification. Cotinine levels were significantly negatively associated with developmental quotients (DQs) of the whole test, and cognitive, language, fine-motor and social subtests of the CDIIT. Lower cognitive and language DQs were found in exposed group with absent type of GSTT1. In addition, the lowest scores in fine-motor and whole test DQs were detected in exposed group with CYP1A1 Ile462Val variant type and GSTT1 absent type. It can be concluded that CYP1A1 Ile462Val and GSTT1 metabolic genes can modify the effect of cord blood cotinine on early child neurodevelopment especially for language and fine motor development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Child Development / drug effects*
  • Child, Preschool
  • Cotinine / blood*
  • Cytochrome P-450 CYP1A1 / genetics
  • Cytochrome P-450 CYP1A1 / metabolism*
  • Female
  • Fetal Blood / metabolism*
  • Glutathione Transferase / metabolism*
  • Humans
  • Infant, Newborn
  • Isoleucine / genetics*
  • Language
  • Linear Models
  • Male
  • Motor Activity / genetics
  • Neuropsychological Tests
  • Pregnancy
  • Prenatal Exposure Delayed Effects
  • Prospective Studies
  • Taiwan
  • Valine / genetics*


  • Isoleucine
  • Cytochrome P-450 CYP1A1
  • glutathione S-transferase T1
  • Glutathione Transferase
  • Valine
  • Cotinine