Relationship Between Polymorphisms Of One Carbon Metabolic Enzyme Gene And The Metabolic Capacity Of Arsenic Methylation And The Risk Of Arsenic Poisoning In Drinking Water Arsenic Exposure Population

Objective: Arsenic is a metallic element,and persistent exposure to arsenic in the environment poses a great threat to public health.Arsenic,a human carcinogen,ranked no.1 on the U.S.registry of poisons and diseases’ 2017 list of toxic substances(ATSDR 2017).The affected areas of arsenic exposure in China involve many provinces,and the affected population is up to 20 million.In human body,inorganic arsenic is methylated under the catalysis of arsenic-metabolism-related enzymes and the participation of s-adenosylmethionine(SAM),and then transformed into momomethylated aresnic(MMA)and dimethylated aresnic(DMA).Among the metabolites,MMA3+ is the most toxic,followed by DMA3+.However,the amount of SAM in the body will significantly affect the metabolism level of inorganic arsenic.SAM mainly comes from the one carbon unit metabolic loop.This pathway folinic acid(methyl cyclization hydrolase(methylenetetrahydrofolate cyclase,MTHFD),5,10-methylene four hydrogen folic acid reductase(5,10-methylenetetrahydrofolate reductase,MTHFR),methionine synthetase(methionine synthetase,MTR)and methionine synthase reductase(methionine synthetaseReductase(MTRR)gene polymorphism can affect the SAM production process to different degrees,and then indirectly affect the human body’s metabolism ability to arsenic.Studies have shown that even arsenic exposure the same,not all individuals have showed signs of poisoning,and toxic reaction of the illness weight degree between the research object is inconsistent,there are significant individual differences,such differences also hints of genetic material between individual differences in the process of arsenic poisoning can lead to different results.However,the existing researches on the enzyme gene of the metabolic pathway of one carbon unit are relatively simple,and most of them only explore a certain site of a single gene.Therefore,our research in Yunnan some village of China chronic type drinking water arsenic exposurepopulation information,explore indirectly involved in the metabolism of arsenic methylation one carbon unit in the pathway a common site of related enzyme gene polymorphism and metabolism of the body of arsenic methylation ability and sex skin damage occurs,the relationship between the risk of arsenic results can provide data support for the expansion of our country in this field.Methods: Selection of research subjects: The location is a hot spring drinking water type arsenic exposure village in Dali City,Yunnan Province.The criteria for entering the study are: 1 The research object grew up in the village and has no history of field residence or long-term work out;2 They haven’t eaten seafood and arsenic-containing drugs such as Niuhuang Jiedu tablets one week before the investigation.Questionnaire survey: Before the survey,all investigators involved in data collection should be trained,and they can only enter the site to carry out work if they are qualified.The information collected through the questionnaire includes: 1)basic data of the respondents: gender,age,ethnicity,occupation,etc.2)drinking water history: type of current drinking water source,type of original drinking water source,drinking time,etc.3)disease history: past history,medication history,history of present illness,etc.Physical examination: The physical indexes of the subjects were examined by professional investigators,and the suspected arsenic poisoning patients were diagnosed according to the Chinese diagnostic standard for arsenic poisoning(WS/t211-2001).Quality control: In order to avoid bias in the survey,this study requires all participants to receive professional training before the survey,ask questions one by one according to the pre-prepared questionnaires,and resolutely stop the induced survey.In the process of filling in the questionnaire,investigators should carefully check the survey information to avoid missing items and filling in the wrong.Urine collection: The collected random urine samples were first marked and placed in the carrying ice box and quickly transported to the adjacent laboratory where they were frozen in a-20 ° C refrigerator.After the sample collection work is completed,it will be transported back to the school center laboratory in the-80 °C refrigerator for storage and subsequent analysis.Oral swab collection: Several swabs scraped into the abscissor cells of oral mucosa were put into the sampling tube and sealed,indicating the sample number and sampling date.After the survey on that day,the swabs were quickly transported to a nearby laboratory and stored in a dry and cool place.Determination of urinary arsenic concentration: Determination of morphological arsenic content in urine was performed by hydride generation-cold well capture and collection-atomic absorption spectrophotometry.Genotype analysis: The Typer software was used to automatically interpret the molecular weight peak detected by mass spectrometry and convert it into a mass spectrum peak map corresponding to the molecular weight of the SNP site to generate information related to the SNP locus.Statistical methods: SPSS22.0 software was used to establish the database,analyze and process the data,and P<0.05 was considered as significant difference with statistical significance.Results: 1.The subjects of this study were from several natural villages in midu county,yunnan province,and the total number of subjects who did not meet the inclusion criteria was 289.Among them,115 were male,accounting for 39.8%,174 were female,accounting for 60.2%.The percentage of drinkers and smokers was18.0% and 23.9% respectively.There were 53 patients(18.3%)with arsenic-induced skin injury.2.The effect of gene mononucleotide polymorphism on the body’s arsenic metabolism: the results of linear regression analysis showed that the SNP mutation at rs9651118 of MTHFR could significantly increase MMA% level and decrease SMR level.The SNP mutation at rs1801394 of MTRR could significantly increase iAs%level,decrease DMA% level and decrease FMR level.3.Influence of gene mononucleotide polymorphism on the risk of arsenical skin injury: the results of multivariate Logistic regression analysis showed that after adjusting for confounding factors such as age,gender,smoking,drinking and urine tAs,there was no significant correlation between the above gene mononucleotide polymorphism and skin injury caused by arsenic exposure.Conclusion: 1.MTHFR rs9651118 mutant(TC/CC)can significantly increase MMA% level and reduce SMR level.MTRR rs1801394 mutant type(AG/GG)cansignificantly increase iAs% level,reduce DMA% and FMR level.2.MTHFR(rs1801131,rs1801133,rs9651118),MTHFD(rs1950902,rs2236225)and MTRR(rs1801394)6 loci polymorphisms had no significant effect on the risk of arsenic skin lesions.