Polymorphism study of nine SNPs associated with subjective response to alcohol in Chinese Han, Hui, Tibetan, Mongolian and Uygur populations

Heavy alcohol drinking is a major public health problem,causing a large disease,social and economic burden in societies.Subjective response (SR) to alcohol is an intermediate characteristic of heavy drinking.A variety of candidate genes have been reported to be associated with SR to alcohol.In this study,we investigated nine single nucleotide polymorphisms (SNPs) related to SR to alcohol in healthy individuals from five Chinese ethnic groups,the Han,Hui,Tibetan,Mongolian and Uygur populations,and a total of 584 bloodstain samples were collected.The nine SNPs included four SNPs in alcohol-metabolizing genes (ADH1B,ADH1C,ALDH2 and CYP2E1*5B) and five SNPs in genes of neurobiological pathways (GABRA2,OPRM1,CHRNA3,HYKK and SLC6A4).A SNaPshot analysis method was developed to type these SNPs simultaneously,and all samples were typed successfully.Statistical analyses of the allele frequencies indicated that the frequencies of all SNPs,except for ADH1C,showed varying degrees of difference in the five studied ethnic groups.Tibetans showed the highest frequencies of risk alleles for heavy drinking at most loci.The genetic polymorphic differences found in this study revealed the variation in genetic susceptibility to heavy drinking in the studied populations.

A Preliminary Gas Chromatography‑Mass Spectrometry‑Based Metabolomics Study of Rats Ingested Diazepam or Clonazepam

Drug-facilitated sexual assault(DFSA)is a sexual act in which the victim is unable to give or rescind consent due to alcohol or drug intoxication,which involved the abuse of benzodiazepines around the world.Conventional techniques used for the analysis of benzodiazepines have the limitation of short detection time window due to the rapid metabolism of these drugs in body.This study aimed to investigate the characteristic changes of metabolites in the blood of rats after ingesting diazepam/clonazepam through a gas chromatography-mass spectrometry-based metabolomics method,allowing the indirect reveal of the rats ingested diazepam/clonazepam.First,we found that diazepam and clonazepam in the blood of rats could not be detected by liquid chromatography-tandem mass spectrometry after 48 h of ingestion.Then,orthogonal partial least squares discrimination analysis regression models were,respectively,constructed to determine whether the rats ingested diazepam/clonazepam after 48 h.The results showed that 5 metabolites were found to be associated with diazepam exposure,and 7 metabolites were found to be associated with clonazepam exposure,which may be characterization for the evaluation of digestion of diazepam and clonazepam in rat.

A Gas Chromatography-Mass Spectrometry‑Based Metabonomic Study on Estimation of Toxicant in Rats

The aim of this study was to develop a gas chromatography‑mass spectrometry(GC‑MS)‑based metabolomics method to distinguish different kinds of poisons in the blood.We examined the changes in blood metabolites using GC‑MS following administration of four different poisons(paraquat,dichlorvos,aconitine,and sodium nitrite).The data were analyzed with orthogonal partial least squares.Then,total and single differential metabolite profiles were evaluated with support vector machine(SVM)models.The results showed that various metabolites(5‑ketone proline,1,5‑anhydrohexitol,lactic acid,glycine 2,2‑furoic acid,and 3‑hydroxybutyric acid)were differential between the experimental groups and the control groups.The accuracy rates of the SVM models established using total and single differential metabolites were 80%and 100%,respectively.In conclusion,we successfully developed a poison screening method.The established SVM models can distinguish four kinds of poisons and could be used to establish a complete poison metabonomic information database.Furthermore,some of the metabolites could be biomarkers of these poisons.Finally,both the models and potential biomarkers may reduce the time required for poison detection and provide direction for solving cases and auxiliary diagnosis.

Metabolomic Analysis of the Brain and Blood from Rats Exposed to High‑dose Chlorpyrifos

Chlorpyrifos is an organophosphate pesticide used to kill pests such as insects and worms.Wide use of chlorpyrifos has led to serious safety concerns worldwide.Research on the mechanism of action of chlorpyrifos poisoning is continuing.We investigated changes in the small‑molecular metabolites in the brain and blood of rats upon exposure to chlorpyrifos at an acute‑poisoning dose.Rats were given twice the lowest dose of chlorpyrifos that is lethal for 100%of exposed animals(2×LD_(100))and then killed after 2 h.After treatment,gas chromatography‑mass spectrometry was used to analyze the metabolomic changes in the brain and blood samples of rats.An increase in blood levels of creatinine and uric acid were noted,along with a decrease in levels of various amino acids.These changes suggested that chlorpyrifos exposure may damage kidney function and cause disorders in amino‑acid metabolism of rats.Decreased concentrations of gamma‑aminobutyric acid and niacinamide in the brain and increased concentrations of 3‑hydroxybutyric acid in rats with acute poisoning by chlorpyrifos were observed,which may suggest oxidative damage in the body.