A case-control study of CYP1A1, GSTT1 and GSTM1 gene polymorphisms, pregnancy smoking and fetal growth restriction.

OBJECTIVES: To determine the role of maternal CYP1A1, GSTT1, and GSTM1 metabolic gene polymorphisms in modulating the association between pregnancy smoking exposure and fetal growth restriction. STUDY DESIGN: A case-control study was conducted to investigate if the association of pregnancy smoking and birth outcome was modulated by maternal gene polymorphisms. A total of 90 mothers with an IUGR baby (cases) and 180 mothers without IUGR (controls) were enrolled. RESULTS: Almost half of smokers who carried a CYP1A1 variant (51.3%), GSTT1 null (43.6%), or GSTM1 null genotypes (64.1%) delivered a baby with IUGR. Smokers with the variant CYP1A1 "aa" genotype had babies with lower mean birthweight than non-smokers with the same genotype (p=0.004). An interaction test showed increased prevalence of IUGR in smokers with the CYP1A1 (Aa/aa) variant (adjusted OR, 1.9; 95% CI, 1.4-5.5, p=0.01), or with the GSTT1 null (AOR, 1.5; 1.1-3.1, p=0.001), or GSTM1 null genotypes (AOR, 1.5; 1.2-3.7, p=0.001). CONCLUSIONS: Risk of fetal growth restriction in mothers who smoked during pregnancy was modulated by maternal metabolic gene polymorphisms. The genetic control of the conversion of toxic metabolites of tobacco smoke to less damaging substances is important for maternal and fetal health.

Prenatal alcohol exposure, CYP17 gene polymorphisms and fetal growth restriction.

OBJECTIVE: To determine the association of maternal CYP17 gene polymorphisms and prenatal alcohol consumption with intrauterine growth restriction (IUGR). STUDY DESIGN: A case-control study in singleton livebirths was conducted at the Liverpool Women's Hospital between 2004 and 2005. Cases (n=90) were mothers with an IUGR baby and controls (n=180) those with a normal birthweight infant. Maternal genomic DNA was extracted from buccal smears and PCR (RFLP) was used for genotyping. RESULTS: Amongst cases, the prevalence of the maternal CYP17 homozygous wild type "A1A1", heterozygous "A1A2" and homozygous "A2A2" variants was 36.7%, 47.7% and 15.6%, which did not differ significantly from their prevalence amongst controls (p=0.6). The proportion with prenatal alcohol exposure was significantly higher in cases than controls (45.6% versus 30.6%, p=0.01). Mean birthweight was significantly lower in mothers with the CYP17 A1A1 genotype compared to those with variant genotypes (A1A2/A2A2) in both the alcohol-exposed (p=0.03) and non-exposed groups (p=0.01). In all women regardless of genotype, IUGR risk increased in mothers exposed to alcohol during pregnancy (OR, 2.9, 95% CI; 1.8-4.2, p=0.01). There was a significant interaction between the CYP17 A1A1 genotype and prenatal alcohol consumption for fetal growth restriction (adjusted OR, 1.4, 95% CI; 1.1-1.9, p=0.04). CONCLUSION: The association between prenatal alcohol exposure and intrauterine fetal growth restriction was modulated by the maternal CYP17 A1A1 genotype.