Influence of CYP2A6*4 genotypes on maternal serum cotinine among Chinese nonsmoking pregnant women

Introduction: Serum cotinine is a common biomarker for smoking and secondhand smoke (SHS) exposure, but it can be affected by the activity of nicotine-metabolizing enzymes. This study investigated the influence of CYP2A6*4 genotypes on serum cotinine among nonsmoking pregnant women. Methods: We analyzed the data from 545 Chinese nonsmoking pregnant women in a case-control study on SHS exposure and birth outcomes in southern China. Participants self-reported their status and duration of SHS exposure during pregnancy right after delivery in hospital. Research staff used polymerase chain reaction to genotype CYP2A6*4 and enzyme-linked immunosorbent assay to measure cotinine levels in maternal serum samples collected before delivery. We stratified women by their selfreported SHS exposure status and CYP2A6*4 genotypes and then compared their median levels of serum cotinine. Results: Among women who self-reported non-SHS exposure (n = 317), the median serum cotinine levels were 2.83 ng/ml for those with CYP2A6*1/*1 genotype, 1.39 ng/ml for CYP2A6*1/*4, and 0.77 ng/ml for CYP2A6*4/*4, respectively. Among women who self-reported SHS exposure (n = 228), the median cotinine levels were 3.32 ng/ml for those with CYP2A6*1/*1 genotype, 2.38 ng/ml for CYP2A6*1/*4, and 1.56 ng/ml for CYP2A6*4/*4, respectively. Strikingly, self-reported SHS-exposed women with CYP2A6*1/*4 or CYP2A6*4/*4 genotype had significantly lower (rather than higher) median cotinine levels than self-reported non-SHS-exposed women with CYP2A6*1/*1 genotype (p = .012). Conclusions: CYP2A6*4 genotype is associated with lower serum cotinine among Chinese nonsmoking pregnant women. Measuring CYP2A6*4 genotype may help to improve the validity of SHS exposure measurement by serum cotinine in pregnant women and possibly also in other nonpregnant populations.