Modification of adverse health effects of maternal active and passive smoking by genetic susceptibility: Dose-dependent association of plasma cotinine with infant birth size among Japanese women-The Hokkaido Study.

Objectives: We aimed to assess the individual dose-response effects of eight maternal polymorphisms encoding polycyclic aromatic hydrocarbon-metabolizing and DNA-repair genes on prenatal cotinine levels according to infant birth size.

Methods: In total, 3263 Japanese pregnant women were assigned to five groups based on plasma cotinine levels during the 8th month of pregnancy, as measured using ELISA (cut-offs: 0.21, 0.55, 11.48, and 101.67ng/mL). Analyses were performed using multiple linear regression.

Results: Birth weight reduction showed a dose-dependent relationship with prenatal cotinine levels (P for trend<0.001). When considering the specific aromatic hydrocarbon receptor (AHR) (G>A, Arg554Lys; db SNP ID: rs2066853) and X-ray cross-complementing gene 1 (XRCC1) (C>T, Arg194Trp, rs1799782) genotypes, a larger birth weight reduction was noted among infants born to mothers with the highest cotinine level.

Conclusion: Infants born to women with specific AHR and XRCC1 genotypes may have higher genetic risks for birth weight reduction.