Metallothionein 2A gene polymorphism and trace elements in mother-newborn pairs in the Croatian population.

The main source of exposure for all essential and toxic elements in the general population is diet. In smokers, the main route for cadmium (Cd) and lead (Pb) intake is the inhalation of tobacco smoke. Besides gender, age, nutrition, lifestyle, and physiological conditions such as pregnancy, specific genetic characteristics also influence individual element uptake. Metallothionein MT2 is a cysteine-rich low-weight protein found ubiquitously throughout the body. Specific gene polymorphism may influence MT2 expression and subsequent binding, transfer and organ accumulation of metals, though data on these influences are lacking, especially in human mother-newborn pairs. The objective of this study was to determine selected toxic (Cd, Pb, Hg) and essential (Fe, Zn, Cu, Se) elements in maternal blood, placenta, and cord blood (by ICP-MS), and MT2 levels in maternal serum (by ELISA) in relation to maternal MT2A -5A/G (rs28366003) polymorphism (by RFLP-PCR and electrophoresis). Study participants were healthy postpartum women in Croatia (n=268, mean age 29 years) with term vaginal childbirth in a maternity ward assigned into two study groups by self-reporting about their smoking habit (by questionnaire). Smokers vs. non-smokers had increased levels of Cd and Pb in all measured samples, Fe and Cu in cord blood, Zn in placenta, and MT2 in maternal serum. Among subjects with AG/GG genotype, placental Fe was significantly lower only among non-smokers, while MT2 levels in serum were lower, though not significantly, regardless of maternal smoking habit. There was no impact of MT2A -5A/G SNP on any element in maternal or cord blood. In conclusion, the results confirmed maternal smoking-related increases in Cd and Pb levels in the maternal-placental-foetal unit. They also provided additional data on concomitant metal concentrations in representative samples of maternal blood, placenta, and cord blood, as well as increased cord blood Fe and Cu, placental Zn, and maternal serum MT2 in smokers. New evidence is that MT2A -5A/G SNP was associated with decreased placental Fe levels in non-smokers. For a final conclusion on the influence of the MT2A -5A/G polymorphism on toxic and essential element levels in mother-newborn pairs, further research would require a larger number of participants divided across subgroups defined by the main source of particular toxic metal exposure (such as specific food intake, cigarette smoking, air pollution and/or occupational exposure).