Maternal smoking during pregnancy and genetic polymorphisms in the Ah receptor, CYP1A1 and GSTM1 affect infant birth size in Japanese subjects

Abstract

Genetic susceptibility to tobacco smoke might have relation to adverse pregnancy outcomes. To estimate the effects of maternal smoking and genetic polymorphisms on infant birth weight and length, we conducted a prospective cohort study of 293 women who delivered singleton live births in Sapporo, Japan. Birth weight and length were significantly lower among infants born to continuously smoking women having the aryl hydrocarbon receptor (AhR) wild type genotype (Arg/Arg; 211 g +/- 76 g; 1.2 cm +/- 0.4 cm, p < 0.01 and p < 0.01, respectively), the CYP1A1 variant genotype (m1/m2 + m2/m2; 170 g +/- 64 g, 0.8 cm +/- 0.3 cm, p < 0.01 and p < 0.05, respectively), or the GSTM1 null genotype (171 g +/- 58 g, 0.6 cm +/- 0.3 cm, p < 0.01 and p < 0.05, respectively). When combinations of these genotypes were considered, birth weight and length were significantly lower for infants of continuously smoking women in the AhR wild type + CYP1A1 variant group (315 g +/- 116 g; 1.7 cm +/- 0.6 cm, p < 0.01 and p < 0.01, respectively) and in the CYP1A1 variant + GSTM1 null group (237 g +/- 92 g; 1.3 cm +/- 0.5 cm, p < 0.05 and p < 0.01, respectively). These genotypes did not confer adverse effects among women who had never smoked; therefore, maternal smoking in combination with maternal AhR, CYP1A1 and GSTM1 genetic polymorphisms may adversely affect infant birth size.

Effects of the Interaction between Interleukin-6-634C/G Polymorphism and Smoking on Serum C-Reactive Protein Concentrations

“…A possible reason for the lack of a −634C/G genotype effect on CRP concentrations in current smokers is that continuous smoking, which stimulates inflammation, could reduce the −634G allele's effect on CRP concentration; the −634G allele may increase CRP concentration when smoking does not stimulate inflammation. Also, glutathione S-transferase (GST) M1 and P1, phase II detoxification enzymes, were related to increased risk of smokingrelated diseases (29,30) and to the metabolism of many carcinogenic compounds in tobacco smoke (31). It has been reported that the GSTM1 and GSTP1 gene polymorphisms are related to inflammation (32).…”

Molecular interactions between the Wilms' tumor transcription factor and the aryl hydrocarbon receptor during nephrogenesis and its impact on fetal programming of renal disease.

“…Interestingly, variants of enzymes regulated by AHR activity (CYP1A1 m1/m2 + m2/m2) or linvolved in PAH elimination (GSTM1 -1-) sensitized fetuses to the effects of maternal smoking (Sasaki et al, 2006). This study directly links PAH exposure to deficits in AHR signaling in the context of fetal programming.…”

“…Relevant to our studies is that expression of AHR protein with af!~/arg at codon 211 sinnificantly lowered birth weight and length in offspring exposed to in utero tobacco smoke (Sasaki et a/., 2006). Interestingly, variants of enzymes regulated by AHR activity (CYP1Al m1/m2 + m2/m2) or involved in PAH elimination (GSTM1 -/-) sensitized fetuses to the effects of maternal smokin!~ (Sasaki et al, 2006). This study directly links PAH exposure to deficits in AHR signaling in the context of fetal pronramming.…”

“…The discovery of potent, environmental chemicals that act as AHR ligands has revealed that dysregulation of AHR function during embryonic development can have deleterious effects. Of relevance to this project, from a medical perspective, are epidemiological reports that maternal exposure to environmental tobacco smoke, a complex mixture of chemicals containing high concentrations of ligands of the AHR such as polycyclic aromatic hydrocarbons (PAH), mediates developmental abnormalities (Sasaki et al, 2006). Also of note is that children of parents who work in occupations associated with increased exposure to AHR ligands have a higher incidence of Wilms' tumors (Olshan et al, 1990).…”

“…While our exposure regimen did not result in gross embryonic deficiencies, as measured by resorption, death, or morphological organ abnormalities, subtle BaP-induced differences become manifest as decreased glomerular numbers and compromised renal function. These deficits are relevant to the development of adult onset renal dlisease (Sasaki et al, 2006;Zandi-Nejad et al, 2006 In fact, glomerulopathies are the most common causes of end-stage renal disease worldwide (Hricik et a/., 1998). The impact of in utero BaP exposure on other glomerular cell populations such as mesangial and endothelial cells remains to be determined.…”