Maternal smoking, GSTT1 and GSTM1 polymorphisms and infant birth-weight reduction in a Kaunas cohort study

Abstract

Background and Objective. A number of environmental factors, including smoking and xenobiotic metabolising genes, have been associated with birth outcomes. However, only limited data are available on the molecular mechanisms underlying foetal growth. We examined the association between tobacco-smoke exposure during pregnancy and birth weight of the infant among genetically susceptible women in Kaunas, Lithuania. Methods. We carried out an epidemiological study including 527 women. The gene GSTM1- and GSTT1- null genotypes were identified by the multiplex polymerase chain reaction in peripheral blood DNA samples. We evaluated associations with a multiple linear-regression model, adjusting for gestational age, maternal education, family status, body mass index, blood pressure, and parity. Results. We found that among Lithuanian women, the prevalence of the GSTT1-null genotype is 16.8%, GSTM1-null ─ 46.1% and the carriers of the double-null genotypes comprised 8.7% of the total population studied. The findings suggested a non-significant birth-weight reduction among light smoking mothers (mean: 6 cigarettes/day) with the GSTT1-null genotype (-149.4 g, P = 0.129) and those with the GSTM1-null genotype (-117.5 g, P = 0.145). Double-null genotype for both GSTT1 and GSTM1 among the smokers showed a synergistic effect and the interaction between these genes was associated with a 309.3-g reduction in birth weight (P = 0.029). Conclusion. The study shows the synergistic effect of the GSTT1 and GSTM1 double-null genotypes on reduction in birth weight among smoking women and presents evidence that carriers of the double null genotypes should be treated as an increased susceptibility group for adverse pregnancy outcomes. Our data also indicate that identification of the group of susceptible subjects should be based on both environmental exposure and gene polymorphism.