Impact Of Arsenic Methylation Metabolic Enzyme Gene Polymorphism On Its Methylation Capability And Risk Of Arsenic-induced Skin Injury

Introduction:Arsenic is a carcinogen recognized by the World Health Organization's International Agency for Research on Cancer.Long-term consumption of high arsenic water can cause bladder cancer,liver cancer,lung cancer and skin cancer.Due to the wide range of exposure to drinking water and arsenic,the threat of population and the seriousness of the disease,it has become a serious public health problem.The methylation and metabolism process of inorganic arsenic into the body in the liver is:pentavalent inorganic arsenic(iAs⁵⁺)enters the body and undergoes two reductions to form trivalent monomethyl arsenic(MMA³⁺),which is then oxidized and methylated to form five.The valence of dimethylarsenic(DMA⁵⁺)is finally reduced to trivalent dimethylarsenic(DMA³⁺)with DMA³⁺as the final product.Under the same level of exposure to drinking water,the population is not all sick and the severity of the symptoms of the disease caused by arsenic exposure varies from person to person.Therefore,we can further speculate that in addition to individual factors,genetic factors also play an important role in the pathogenesis of arsenic poisoning.The genetic factors are mainly the polymorphisms of methylation-metabolizing enzyme genes.The polymorphisms directly involved in the arsenic methylation metabolic enzyme gene have the greatest influence on the arsenic methylation metabolism and the risk of arsenic poisoning,such as PNP.GSTO,AS3MT.This study focused on the role of arsenic methylation metabolic enzyme gene polymorphism in its methylation metabolism and risk of arsenic skin lesions.At present,there are few studies in this field at home and abroad and the research results are not the same and controversial.In summary,the arsenic methylation metabolic enzyme gene polymorphism and human arsenic methylation metabolism and arsenic are discussed by collecting relevant data from a drinking water-type arsenic exposure area in Midu County,Dali City,Yunnan Province,China.The relationship between the risk of skin damage and the results of the study can provide Chinese population data for the research field.Methods:1.Selection of research subjects:The location of this survey was a hot-type high-arsenic exposed village in Midu County,Dali City,Yunnan Province.The criteria were included:1)The villagers required to be investigated grew up in the village and did not have long-term working or living history.2)The villagers surveyed were asked to have no history of consumption of arsenic-containing foods and arsenic-containing drugs during the week prior to the investigation.Exclusion criteria:Excludes diseases such as chronic liver disease and kidney disease that can affect the metabolism of arsenic methylation.Questionnaire survey:All investigators should be professionally trained before conducting an investigation.Only qualified for training can participate in the next survey.The information collected in this survey includes:1)Personal information of the respondents:age,gender,ethnicity,etc.2)Drinking water:drinking water,drinking water sources,etc.3)History of disease:past medical history,medication history,current medical history,etc.4)Lifestyle:smoking history,drinking.Health check:The professionally trained investigators will conduct a physical examination on the population.The diagnostic criteria for arsenic poisoning in China?WS/T211-2001?is the distinction between the diagnostic criteria for suspected cases of arsenic poisoning and the level of arsenic poisoning.Sample collection:The collection of andom urine urine samples and buccal swabs should be carried out simultaneously with the health check,and should be marked after collection.After the day's work is completed,the collected samples will be shipped to the nearest laboratory and frozen in a refrigerator at-20?.After all samples have been collected,the samples are shipped back to the laboratory and placed in a-80?freezer for subsequent analysis.Determination of urinary arsenic concentration:The arsenic content in urine was measured by hydride generation-cold well trapping-atomic absorption spectrophotometry in units of?g/L.Determination of urinary arsenic concentration:The arsenic content in urine was measured by hydride generation-cold well trapping-atomic absorption spectrophotometry in units of?g/L.Genotype analysis:The mass spectrometry peaks detected by mass spectrometry were automatically interpreted using Typer software,and the mass spectrometry peaks of the molecular weights corresponding to the SNP sites were transformed to detect the SNP locus information.Quality Control:In order to reduce the errors generated during the course of this survey,this study requires all participants to participate in the survey to receive professional training before participating in the survey.In the course of the investigation,the personnel involved in the investigation should make inquiries according to the work manual and resolutely put an end to the persuasive questions.Investigators should carefully check the survey information when filling out the questionnaire to avoid missing items and filling in errors.During the health checkup process,strict diagnosis of arsenic poisoning is required to comply with the Chinese Diabetes Diagnostic Criteria?WS/T211-2001?.Statistical methods:The database was established with SPSS22.0 statistical software,and the data was statistically analyzed.The difference was statistically significant at P<0.05.Results:1.The study was conducted from a hot spring-type high-arsenic exposed village in Midu County,Dali City,Yunnan Province,with a total of 289 samples.The average level of urine tAs in this population was 115.14 ug/L.Among them,115 were men,accounting for 39.8%,and 174 were women,accounting for 60.2%.The proportion of smoking and drinking was 23.9%and 18.0%respectively.There were53 patients with arsenic-induced skin lesions,accounting for 18.3%.This study examined the polymorphism of 9 genes in 4 samples of this population.Nine SNP loci satisfy the Harvard equilibrium law?P>0.05?.2.Linear regression analysis showed that age,gender,smoking,alcohol consumption,and urine tAs were adjusted.SNP mutations in the GSTO1?RS11509438?locus significantly increased the MMA%level?P<0.05?.The 8 SNPs of PNP,AS3MT,GSTO1 and GSTO2 had no significant difference in iAs%,MMA%,DMA%,FMR and SMR between wild type and mutant?P>0.05?.3.Multivariate logistic regression analysis showed that age,gender,smoking,alcohol consumption and urine tAs were adjusted.9 SNPs PNP?RS1049564?,AS3MT?RS10748835,RS3740390,RS3740393,RS7085104,RS11191439?,GSTO1?RS4925,RS11509438?and GSTO2?RS156697?of PNP,AS3MT,GSTO1 and GSTO2 for skin damage caused by arsenic exposure to drinking water No significant effect?P>0.05?.Conclusion:1.The gene polymorphism of arsenic methylation metabolizing enzyme GSTO1?RS11509438?is related to the ability of arsenic methylation and metabolism.The mutation of this site SNP?CA/AA?can significantly increase the level of MMA%,but to the skin.There was no significant effect on the risk of injury.2.Polymorphisms of PNP?RS1049564?,AS3MT?RS10748835,RS3740390,RS3740393,RS7085104,RS11191439?,GSTO1?RS4925?and GSTO2?RS156697?had no significant effect on the risk of arsenic methylation metabolism and skin damage.