Human exposure to mercury is still a major public health concern. In this context, children have a higher susceptibility to adverse neurological mercury effects, compared to adults with similar exposures. Moreover, there exists a marked variability of personal response to detrimental mercury action, in particular among population groups with significant mercury exposure. New scientific evidence on genetic backgrounds has raised the issue of whether candidate susceptibility genes can make certain individuals more or less vulnerable to mercury toxicity. In this review, the aim is to evaluate a new genetic dimension and its involvement in mercury risk assessment, focusing on the important role played by relevant polymorphisms, located in attractive gene targets for mercury toxicity. Existing original articles on epidemiologic research which report a direct link between the genetic basis of personal vulnerability and different mercury repercussions on human health will be reviewed. Based on this evidence, a careful evaluation of the significant markers of susceptibility will be suggested, in order to obtain a powerful positive “feedback” to improve the quality of life. Large consortia of studies with clear phenotypic assessments will help clarify the “window of susceptibility” in the human health risks due to mercury exposure.

Background: Dysfunction of γ-aminobutyric acid (GABA) (B) receptors has been implicated in the pathogenesis of temporal lobe epilepsy (TLE). Objective: To evaluate the genetic contribution of cloned human GABA(B) receptors to TLE. Methods: The authors genotyped 141 patients (78 women and 63 men; mean age = 49.1 ± 18.0 years) with nonlesional TLE and 372 age- and sex-matched normal individuals for the known polymorphism G1465A in the human GABA(B) receptor 1 [GABA(B[1])] gene. Results: There was a highly significant overrepresentation of the G1465A heterozygote in patients with TLE compared with controls. The A/G genotype was found in 17% of the 141 patients with TLE and in only 0.5% of the 372 controls (p < 0.0001). The authors also found that patients carrying the A allele had a significantly higher risk (p = 0.003, OR = 6.47, 95% CI = 2.02 to 20.76) of developing drug-resistant TLE. Furthermore, the age at onset of seizures tended to be lower in patients with A/G genotype, but the difference was not significant. Conclusions: The results of this study indicate that the GABA(B[1]) polymorphism (G1465A) confers a highly increased susceptibility to TLE. Moreover, it seems to influence the severity of this common epileptic disorder.

Objective: To investigate whether polymorphisms in the genes for dopamine receptors D₁ and D₂ are associated with the risk of developing peak-dose dyskinesias in PD. Background: Peak-dose dyskinesias are the most common side effects of levodopa therapy for PD. The identified predictors may only partially account for the risk of developing peak-dose dyskinesias because a substantial proportion of patients never develop peak-dose dyskinesias. Genetic factors could play a role in determining the occurrence of peak-dose dyskinesias. Methods: A case-control study of 136 subjects with sporadic PD and 224 population control subjects. We studied three polymorphisms involving the dopamine receptor D₁ gene and one intronic short tandem repeat polymorphism of the dopamine receptor D₂ gene. Results: The polymorphisms of the dopamine receptor D₁ gene were not associated with the risk of developing PD or peak-dose dyskinesias. The 15 allele of the polymorphism of the dopamine receptor D₂ gene was more frequent in parkinsonian subjects than in control subjects. More important, the frequency of both the 13 allele and the 14 allele of the dopamine receptor D₂ gene polymorphism was higher in nondyskinetic than in the dyskinetic PD subjects. The risk reduction of developing peak-dose dyskinesias for PD subjects carrying at least 1 of the 13 or 14 alleles was 72% with respect to the PD subjects who did not carry these alleles. Conclusions: Certain alleles of the short tandem repeat polymorphism of the dopamine receptor D₂ gene reduce the risk of developing peak-dose dyskinesias and could contribute to varying susceptibility to develop peak-dose dyskinesias during levodopa therapy.

A field campaign was performed simultaneously at five measurement sites, having different characteristics, to characterize the spatial distribution of the carbonaceous content in atmospheric aerosol in Southern Italy during the winter season. Organic carbon (OC) and elemental carbon (EC) were measured at urban (Naples), suburban (Lecce), coastal/marine (Lamezia Terme and Capo Granitola), and remote (Monte Curcio) locations. OC and EC mass concentrations were quantified by the thermal-optical transmission (TOT) method, in 24-h PM₁₀ and PM_2.5 samples collected on quartz fiber filters, from 25 November 2015 to 1 January 2016. The different sites showed marked differences in the average concentrations of both carbonaceous species. Typically, OC average levels (±standard deviation) were higher at the sites of Naples (12.8 ± 5.1 and 11.8 ± 4.6 μg/m³) and Lecce (10.7 ± 5.8 and 9.0 ± 4.7 μg/m³), followed by Lamezia Terme (4.3 ± 2.0 and 4.0 ± 1.9 μg/m³), Capo Granitola (2.3 ± 1.2 and 1.7 ± 1.1 μg/m³), and Monte Curcio (0.9 ± 0.3 and 0.9 ± 0.3 μg/m³) in PM₁₀ and PM_2.5, respectively. Similarly, EC average levels (±standard deviation) were higher at the urban sites of Naples (2.3 ± 1.1 and 1.8 ± 0.5 μg/m³) and Lecce (1.5 ± 0.8 and 1.4 ± 0.7 μg/m³), followed by Lamezia Terme (0.6 ± 0.3 and 0.6 ± 0.3 μg/m³), Capo Granitola (0.3 ± 0.3 and 0.3 ± 0.2 μg/m³), and Monte Curcio (0.06 ± 0.04 and 0.05 ± 0.03 μg/m³) in PM₁₀ and PM_2.5, respectively. An opposite trend was observed for the OC/EC ratios ranging from 6.4 to 15.9 in PM₁₀ and from 6.4 to 15.5 in PM_2.5 with lower values in urban sites compared to remote sites. Different OC-EC correlations, 0.36 < R² < 0.90, were found in four observation sites. This behavior suggests the contributions of similar sources and common atmospheric processes in both fractions. No correlations were observed between OC and EC at the site of Naples. The average secondary organic carbon (SOC) concentrations, quantified using the minimum OC/EC ratio method, ranged from 0.4 to 7.6 μg/m³ in PM₁₀ and from 0.4 to 7.2 μg/m³ in PM_2.5, accounting from 37 to 59% of total OC in PM₁₀ and from 40 to 57% in PM_2.5 with higher percentages in the urban and suburban sites of Naples and Lecce.

Research from JAMA Neurology — Increased Risk for Alzheimer Disease With the Interaction of MPO and A2M Polymorphisms