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

Abstract 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 101.67 ng/mL). Analyses were performed using multiple linear regression. Results Birth weight reduction showed a dose-dependent relationship with prenatal cotinine levels ( P for trend  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.