Combined effects of AHR, CYP1A1, and XRCC1 genotypes and prenatal maternal smoking on infant birth size: Biomarker assessment in the Hokkaido Study

•We examined the association of prenatal smoking and polymorphism with birth size.•Eight genotypes encoding PAH-metabolizing and DNA-repair genes were investigated.•Polymorphisms were analyzed in 3263 healthy pregnant Japanese women.•We observed adverse birth effects with the combination of AHR, CYP1A1 and XRCC1.•Prenatal smoking and AHR/CYP1A1/XRCC1 SNPs are associated with reduced birth size. We investigated the individual and combined effects of maternal polymorphisms encoding the aromatic hydrocarbon receptor (AHR; rs2066853), cytochrome P450 (CYP) 1A1 (rs1048963), and the X-ray-complementing gene 1 (XRCC1; rs1799782) and prenatal smoking in relation to infant birth size. Totally, 3263 participants (1998 non-smokers and 1265 smokers) were included in the study between 2003 and 2007. Two groups of mothers were distinguished by plasma cotinine levels by ELISA measured during the third trimester (cut-off=11.48ng/mL). We conducted data analysis using multiple linear regression models. Infants whose mothers smoked and had AHR-GG, CYP1A1-AG/GG, and XRCC1-CT/TT genotypes weighed, −145g less than those born of mothers who did not smoke and had the AHR-GA/AA, CYP1A1-AA, and XRCC1-CC genotypes (95% CI: −241, −50). We demonstrated that infants whose mothers smoked during pregnancy with the combination of AHR, CYP1A1, and XRCC1 polymorphisms had lower birth size.