SLC19A1 Genetic Variation Leads to Altered Thiamine Diphosphate Transport: Implications for the Risk of Developing Wernicke-Korsakoff's Syndrome.

AIMS: Wernicke-Korsakoff syndrome (WKS) is commonly associated with chronic alcohol misuse, a condition known to have multiple detrimental effects on thiamine metabolism. This study was conducted to identify genetic variants that may contribute to the development of WKS in individuals with alcohol dependence syndrome through alteration of thiamine transport into cells. METHODS: Exome sequencing data from a panel of genes related to alcohol metabolism and thiamine pathways were analysed in a discovery cohort of 29 individuals with WKS to identify possible genetic risk variants associated with its development. Variant frequencies in this discovery cohort were compared with European frequencies in the Genome Aggregation Database browser, and those present at significantly higher frequencies were genotyped in an additional cohort of 87 alcohol-dependent cases with WKS and 197 alcohol-dependent cognitively intact controls. RESULTS: Thirty non-synonymous variants were identified in the discovery cohort and, after filtering, 23 were taken forward and genotyped in the case-control cohort. Of these SLC19A1:rs1051266:G was nominally associated with WKS. SLC19A1 encodes the reduced folate carrier, a major transporter for physiological folate in plasma; rs1051266 is reported to impact folate transport. Thiamine pyrophosphate (TPP) efflux was significantly decreased in HEK293 cells, stably transfected with rs1051266:G, under thiamine deficient conditions when compared with the efflux from cells transfected with rs1051266:A (P = 5.7 × 10-11). CONCLUSION: This study provides evidence for the role of genetic variation in the SLC19A1 gene, which may contribute to the development of WKS in vivo through modulation of TPP transport in cells.

Genetic variants in or near ADH1B and ADH1C affect susceptibility to alcohol dependence in a British and Irish population.

Certain single nucleotide polymorphisms (SNPs) in genes encoding alcohol dehydrogenase (ADH) enzymes confer a significant protective effect against alcohol dependence syndrome (ADS) in East Asian populations. Recently, attention has focused on the role of these SNPs in determining ADS risk in European populations. To further elucidate these associations, SNPs of interest in ADH1B, ADH1C and the ADH1B/1C intergenic region were genotyped in a British and Irish population (ADS cases n = 1076: controls n = 1027) to assess their relative contribution to ADS risk. A highly significant, protective association was observed between the minor allele of rs1229984 in ADH1B and ADS risk [allelic P = 8.4 × 10(-6) , odds ratio (OR) = 0.26, 95 percent confidence interval, 0.14, 0.49]. Significant associations were also observed between ADS risk and the ADH1B/1C intergenic variant, rs1789891 [allelic P = 7.2 × 10(-5) , OR = 1.4 (1.2, 1.6)] and three non-synonymous SNPs rs698, rs1693482 and rs283413 in ADH1C. However, these associations were not completely independent; thus, while the ADH1B rs1229984 minor allele association was independent of those of the intergenic variant rs1789891 and the three ADH1C variants, the three ADH1C variants were not individually independent. In conclusion, the rare ADH1B rs1229984 mutation provides significant protection against ADS in this British and Irish population; other variants in the ADH gene cluster also alter ADS risk, although the strong linkage disequilibrium between SNPs at this location precluded clear identification of the variant(s) driving the associations.

Genetic and environmental interplay in risky drinking in adolescents: a literature review.

AIMS: The aim of the study was to review recent research on the interplay between genes, environment and epigenetic factors in risky drinking in adolescents and the impact of neurobiological determinants on early alcohol-related cognitive deficits in young people. METHODS: Narrative review. RESULTS: There is consensus that the brain and the behaviour are shaped during development by the combined effects of genes, childhood experiences, environment and hormonal variations. Epigenetic factors seem to play a role in linking the expression of genes with stress and external experiences during brain maturation and development. Evidence on the interaction between genes and environmental factors illustrates that, in adolescence, external factors play a more important role than genetic factors on the risk of developing alcohol problems later on in life. CONCLUSIONS: Adolescence is a crucial stage of brain development; intervening early and applying certain prevention programmes may halt the progression of alcohol misuse.

Disease-Modifying Drugs and Breastfeeding in Multiple Sclerosis: A Narrative Literature Review.

Pregnancy-related issues in women with multiple sclerosis (MS) have been receiving increasing attention, with particular interest for the use of disease-modifying therapies (DMTs) before conception, during pregnancy, and postpartum, including breastfeeding. The risk of relapse is higher in the early postpartum period, especially in cases of significant disease activity prior to pregnancy, and thus treatment resumption and/or switching strategies might be necessary. Moreover, breastfeeding provides unmatched health benefits for babies and mothers, and is recommended as the best source of nutrition for infants. Furthermore, a protective role of breastfeeding on MS disease course has not been fully demonstrated and it remains debatable. At the same time, a source of concern is the potential transfer of DMTs into breastmilk and the resulting infant exposure. The use of most DMTs is unlicensed during breastfeeding mainly due to the limited data available on the excretion in human milk and on the effects on infants' exposure. Consequently, women have to face the difficult challenge of choosing between breastfeeding and DMT resumption. The present narrative review summarizes and discusses the available evidence on the safety of DMTs during breastfeeding and the relative approved labels. At the time of diagnosis of MS, specific counseling should be offered to women of childbearing age, making them aware of the possible therapeutic options and their impact on pregnancy and breastfeeding. Women can be encouraged to breastfeed, if clinically feasible, following a review of their medications and clinical status, with a personalized approach.

Integrating ecosystem services into crop protection and pest management: Case study with the soil fumigant 1,3-dichloropropene and its use in tomato production in Italy.

Ecosystems provide the conditions for producing food, regulating water, and providing wildlife habitats; these, among others, are known as ecosystem services (ESs). Food production is both economically and culturally important to southern European farmers, particularly in Italy where farmers grow flavorsome tomatoes with passion and pride. Growers rely on pesticides for crop protection, the potential environmental impact of which is often questioned by regulators and other stakeholders. The European regulatory system for the approval of pesticides includes a thorough evaluation of risks to the environment and is designed to be protective of ecosystems. The consideration of ESs in environmental decision making is a growing trend, and the present case study provides an example of how ESs evaluation could be used to enhance agricultural practices and regulatory policy for crop protection. By attacking plant roots, nematodes may affect the growth and yield of fruit and vegetable crops, and the income earned by farmers at harvest time. Available solutions include chemical treatments such as 1,3-dichloropropene (1,3-D), physical treatments (solarization), and biological treatments (biofumigation). In order to characterize the risks and benefits associated with the use of 1,3-D in crop protection, ESs and socioeconomic analyses were applied to its use in the control of nematodes in tomato cultivation in southern Italy. The present study confirmed the benefits of 1,3-D to tomato production in Italy, with significant positive effects on production yields and farm income when compared to limited and transient potential impacts on services such as soil function. It was confirmed that 1,3-D allows farm income to be maintained and secures tomato production in these regions for the future. Integr Environ Assess Manag 2016;12:801-810. © 2016 SETAC.

Summaries of plenary, symposia, and oral sessions at the XXII World Congress of Psychiatric Genetics, Copenhagen, Denmark, 12-16 October 2014.

The XXII World Congress of Psychiatric Genetics, sponsored by the International Society of Psychiatric Genetics, took place in Copenhagen, Denmark, on 12-16 October 2014. A total of 883 participants gathered to discuss the latest findings in the field. The following report was written by student and postdoctoral attendees. Each was assigned one or more sessions as a rapporteur. This manuscript represents topics covered in most, but not all of the oral presentations during the conference, and contains some of the major notable new findings reported.

Biobased surfactant-like molecules from organic wastes: the effect of waste composition and composting process on surfactant properties and on the ability to solubilize Tetrachloroethene (PCE).

In this work, four surfactant-like humic acids (HAs) obtained from garden lignocellulose wastes and kitchen food wastes mixed with garden-lignocellulose wastes, both before and after composting, were tested for surfactant properties and the ability to solubilize tetrachloroethene (PCE). The waste-derived HAs showed good surfactant properties, lowering the water surface tension from 74 mN m(-1) to 45.4 +/- 4.4 mN m(-1), with a critical micelle concentration (CMC) of 1.54 +/- 1.68 g L(-1), which is lower than many synthetic ionic surfactants. CMC was affected by both waste origin and composting processes. The addition of food waste and composting reduced CMC by adding alkyl-C (measured by CP MAS 13C NMR) and N- and S-HA contents (amide molecules), so that a multistep regression was found [CMC = 24.6 - 0.189 alkyl C - 2.64 (N + S); R2 = 0.77, P < 0.10, n = 6]. The four HAs solubilized PCE at the rate of 0.18-0.47 g PCE/g aqueous biosurfactant. These results were much higher than those reported in the literature for a commercial HA (0.026 g/g), but they were in line with those measured in this work for nonionic surfactants such as Tween-80 (0.69 g/g) and Triton X-100 (1.08 g/g).