Apolipoprotein E genotypes in relation with Hg (MeHg) concentrations in pregnant females
published: May 23, 2017, recorded: April 2017, views: 934
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Apolipoprotein E (apo E, gene APOE) is a lipid binding plasma glycoprotein with central roles in lipid and neuronal metabolism. Some researchers point on its metal-binding and antioxidative properties. It has three major isoforms apo E2, apo E3, and apo E4 encoded by alleles ε2, ε3 and ε4 respectively. A large number of studies estimated, that isoform ε4 allele could be associated with various age related disadvantages (cardiovascular diseases, Alzheimer’s disease, ect). Individuals with ε4 variant are also supposed to be more susceptible to metal toxicity, including methyl mercury (MeHg, CH3Hg+). On the other hand, it is believed that apo E is a global activator of innate immune function and its association with higher concentrations of cholesterol, vitamin D and calcium can be beneficial early in life.
The purpose of present work was to estimate relations between APOE polymorphisms and concentrations of mercury in pregnant females chronically exposed to low or moderate amounts of Hg through seafood consumption during pregnancy.
We used samples and metal concentration data set of Croatian pregnant females (n=222, aged 19-44y, sampling in 3rd trimester) and their newborns (n=176): total Hg and MeHg in maternal hair, urine, milk, peripheral and cord blood. APOE was genotyped in archived maternal leukocytes DNA extracts by hydrolysis probes (TaqMan) pre-designed SNP assay for rs429358 and rs7412. Statistics: STATA. EU projects: PHIME, HEALS.
Mothers were divided in APOE ε4 carriers (genotypes ε3/ε4 and ε4/ε4) and ε4 non-carriers (genotypes ε3/ε3, ε3/ε2 and ε2/ε2). Among them, we identified 17% of ε4 carriers. They had significantly higher geometrical means of mercury in: i) blood (p=0.0165; ε4 carriers 2.6 ng/g vs. ε4 non-carriers 2.0 ng/g), ii) hair Hg (p=0.0107; ε4 carriers 740 ng/g vs. ε4 non-carriers 475 ng/g), and iii) cord blood (p=0.0128; ε4 carriers 4.0 ng/g vs. ε4 non-carriers 2.7 ng/g). After taking into account the influence of possible cofounders like seafood consumption, parity, age, body mass index and smoking the observed higher concentrations of mercury in APOE ε4 carriers were no longer significant. Limitations of the study were: too small number of APOE ε4 carriers, low levels of potentially toxic elements and incomplete status of dental amalgams. According to that the positive associations between APOE and mercury should be reconsidered on larger population with wider ranges of metal exposure and nutritional status.
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