Interaction of the cytochrome P4501A2, SULT1A1 and NAT gene polymorphisms with smoking and dietary mutagen intake in modification of the risk of pancreatic cancer

Aromatic amines, N-nitroso compounds and heterocyclic amines are suspected human pancreatic carcinogens. Cytochrome P450 (CYP) 1A2, N-acetyltransferase (NAT) 1, NAT2 and sulfotransferase (SULT) are enzymes involved in the metabolism of these carcinogens. To test the hypothesis that genetic variations in carcinogen metabolism modify the risk of pancreatic cancer (PC), we investigated the effect of single-nucleotide polymorphisms (SNPs) of the CYP1A2, NAT1, NAT2 and SULT1A1 gene on modification of the risk of PC in a hospital-based study of 755 patients with pancreatic adenocarcinoma and 636 healthy frequency-matched controls. Smoking and dietary mutagen exposure information was collected by personal interviews. Genotypes were determined using the polymerase chain reaction–restriction fragment length polymorphism and Taqman methods. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional multivariate logistic regression analysis. We observed no significant main effects of any of these genes on the risk of PC. The CYP1A2 and NAT1 but not SULT1A1 and NAT2 genotypes showed significant interactions with heavy smoking in women not men. In contrast, a significant interaction between NAT1 genotype and dietary mutagen intake on modifying the risk of PC were observed among men but not women. The OR (95% CI) of PC was 2.23 (1.33–3.72) and 2.54 (1.51–4.25) for men having the NAT1*10 and a higher intake of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and benzo[a]pyrene, respectively, compared with individuals having no NAT1*10 or a lower intake of these dietary mutagens. These data suggest the existence of gender-specific susceptibility to tobacco carcinogen and dietary mutagen exposure in PC

Reduced Gamma Oscillations in a Mouse Model of Intellectual Disability: A Role for Impaired Repetitive Neurotransmission?

Intellectual disability affects 2-3% of the population; mutations of the X-chromosome are a major cause of moderate to severe cases. The link between the molecular consequences of the mutation and impaired cognitive function remains unclear. Loss of function mutations of oligophrenin-1 (OPHN1) disrupt Rho-GTPase signalling. Here we demonstrate abnormal neurotransmission at CA3 synapses in hippocampal slices from Ophn1-/y mice, resulting from a substantial decrease in the readily releasable pool of vesicles. As a result, synaptic transmission fails at high frequencies required for oscillations associated with cognitive functions. Both spontaneous and KA-induced gamma oscillations were reduced in Ophn1-/y hippocampal slices. Spontaneous oscillations were rapidly rescued by inhibition of the downstream signalling pathway of oligophrenin-1. These findings suggest that the intellectual disability due to mutations of oligophrenin-1 results from a synaptopathy and consequent network malfunction, providing a plausible mechanism for the learning disabilities. Furthermore, they raise the prospect of drug treatments for affected individuals

Ten millennia of hepatitis B virus evolution

Hepatitis B virus (HBV) has been infecting humans for millennia and remains a global health problem, but its past diversity and dispersal routes are largely unknown. We generated HBV genomic data from 137 Eurasians and Native Americans dated between similar to 10,500 and similar to 400 years ago. We date the most recent common ancestor of all HBV lineages to between similar to 20,000 and 12,000 years ago, with the virus present in European and South American hunter-gatherers during the early Holocene. After the European Neolithic transition, Mesolithic HBV strains were replaced by a lineage likely disseminated by early farmers that prevailed throughout western Eurasia for similar to 4000 years, declining around the end of the 2nd millennium BCE. The only remnant of this prehistoric HBV diversity is the rare genotype G, which appears to have reemerged during the HIV pandemic.Molecular Technology and Informatics for Personalised Medicine and Healt

Ten millennia of hepatitis B virus evolution

Hepatitis B virus (HBV) has been infecting humans for millennia and remains a global health problem, but its past diversity and dispersal routes are largely unknown. We generated HBV genomic data from 137 Eurasians and Native Americans dated between ~10,500 and ~400 years ago. We date the most recent common ancestor of all HBV lineages to between ~20,000 and 12,000 years ago, with the virus present in European and South American hunter-gatherers during the early Holocene. After the European Neolithic transition, Mesolithic HBV strains were replaced by a lineage likely disseminated by early farmers that prevailed throughout western Eurasia for ~4000 years, declining around the end of the 2nd millennium BCE. The only remnant of this prehistoric HBV diversity is the rare genotype G, which appears to have reemerged during the HIV pandemic

Systèmes d'élevage et risque de pollution azotée. Construction d'un indicateur de risque et application dans la plaine des Vosges

National audienceA method for evaluating and localizing areas where there are risks of diffusing nitrates into the groundwater has been established and linked to the livestock farming system diversity and to their characteristic cropping plans. It has been applied to the 2211 farms present in 1993 in the Vosges plain. This method associates real nitrate leaching measures under farm fields, a livestock farm typology which contains information on the cropping plans, and a geographic information system to locate the information within water resource management units. Currently, the farm types combining big areas in cash crops and a maize forage system present the highest potential risks of nitrate pollution, while the farm types specialised in grassland dairy and/or meat production seem to be the least polluing. The farm type location makes it possible to identify geographic areas exposed to a high agricultural nitrate pollution risk, which are characterized by a combination of the most modernised and intensive farm types of the region.Une méthode d’évaluation et de localisation des risques de pollution nitrique diffuse des eaux souterraines, liés à la diversité des systèmes d’élevage de ruminants et à leurs assolements caractéristiques, est mise au point et appliquée sur les 2211 exploitations présentes en 1993 dans la plaine des Vosges. Cette méthode associe des mesures des lixiviations nitriques réelles sous des parcelles agricoles, une typologie des exploitations d’élevage qui contient des informations sur les assolements et un système d’information géographique qui permet de localiser les informations au sein d’unités territoriales de gestion des ressources en eau. Les exploitations combinant des surfaces importantes en grandes cultures et un système fourrager à base de maïs génèrent actuellement les plus forts risques de pollution par les nitrates, alors que les exploitations spécialisées dans les productions de lait et/ou de viande à base d’herbe apparaissent les moins polluantes. La localisation des types d’exploitation permet d’identifier des zones géographiques exposées à un fort risque de pollution d’origine agricole, caractérisées par une combinaison des types d’exploitation d’élevage les plus modernisés et intensifs de la région