HoGG1 Gene Methylation,Gene Polymorphisms And Transcriptional Regulation Of Target Genes In The Role Of Liver Damage Caused By Arsenic

Objective To explore coal-burning arsenic exposure to people of whole blood hOGGl gene promoter 5' CPG island hypomethylation change,and gene polymorphism and the target gene transcription regulation,and the relationship between oxidative damage in the process of liver damage,provide scientific basis for the study of the molecular mechanism of arsenic poisoning.Methods In endemic coal-pollution-borne arsenism area,Xinren county,Guizhou province,according to the diagnostic criteria of endemic araenism(WS/T211-2001),207 people with endemic arsenism were selected.64 residents were selected as controls in avillage about 12km away from the endemic arsenism area.Informed consent,collectting whole blood of objects,methylation-specolic polymerase chain reaction(MSP)were respectively performed to analyze hOGGl hypermethylation in arsenism all respondents.Polymerase chain reaction-restrisction fragment length polymorphism(PCR-RFLP)detect hOGG1 Ser326Cys gene polymorphism.The mRNAexpressions of hOGG1 and APE1 and XRCC1 were detected by real-time quantitative reverse transcription polymerase chain reaction(Real-time PCR).Chemical method respectively to detect the activity of super oxide dismutase(SOD),glutathione peroxidase(GSH-Px),and the contents of malondialdehyde(MDA)in the blood of patients were measured and analysed,and the contents of 8,hydroxy,2 '-deoxyguanine(8_OHdG)urine of patients were measured and analysed.?To analyze hOGG1 gene methylation in arsenic poisoning liver damage,and divided into four groups:Non-case group:46 caces,No obvious hepatopathy group:49 cases,Mild hepatopathy group:65 cases and Moderate-severe hepatopathy group:47cases.?To analyze the relationship between hOGGl gene polymorphism and arsenic poisoning liver damage,objects was based on hOGG1 gene polymorphism detection results,observed objects was divided into Ser/Ser group(wild type 139 cases)and Ser/Cys + Cys/Cys group(mutant type 68 cases).?To analyze the relationship between hOGGl gene methylation and oxidative stress,and based on hOGG1 methylation status,objects was divided into hOGG1 gene methylation group(33 cases)and hOGG1 gene no methylation group(174cases).Results ?The positive rate of hOGGl gene promoter CpG island hypermethylation was 1.56%in contrals,and 4.35?14.28?18.46?25.53%in non-case group,no obvious,mild,moderate-severe hepatopathy groups,the differences were statistically significant(P<0.05).? Liver damage group and non-liver damage group hOGG1Ser326Cys polypeptide sites Ser/Ser,Ser/Cys + Cys/Cys genotype constitute respectively:54.60?45.40?69.77?30.23%,the difference was statistically significant(P<0.05).?hOGGl positive rate of methylated of Ser/Ser group and Ser/Cys + Cys/Cys group were 5.75%and 36.76%,the difference was statistically significant(P<0.05).Ser/Cys + Cys/Cys group susceptibility of high hOGGl gene methylation is 4.9 times of Ser/Ser group(OR=9.5,95CI:3.9?22.6).? hOGG1,APE1,XRCC1 mRNA transcription expression of Methylation group was significantly lower than the methylation,the difference was statistically significant(P<0.05).?hOGG1,APE1 and XRCC1 mRNA expression in Ser/Ser group and Ser/Cys + Cys/Cys group was no significant difference P>0.05).? hOGG1,APE 1 and XRCC1 mRNA expression of Mild hepatopathy group and Moderate-severe hepatopathy group was significantly lower than controls group(P<0.05).?Comparing with negative group,SOD[(79± 16)kU/L],GSH-Px[(72±26)kU/L]activity and 8_OHdG[(22.1 ± 2.3)ug/L]contents were lower[(105±31)kU/L,(175±40)kU/L,(25.3±3.6)ug/L.P<0.05)]in positive group.There was no significant difference between the MDA content(P>0.05).?Mild hepatopathy group and Moderate-severe hepatopathy group,Methylation of serum SOD,GSH-Px levels significantly lower than the methylation group(P<0.05),8-OHdG urine levels increased significantly(P<0.05),no difference between the others(P>0.05).Conclusion ?Coal-burning arsenic exposure to people hOGG1 gene high methylation,inhibit the expression of mRNA transcription,DNA damage may affect the recognition function,thereby inhibiting APE1,XRCC1mRNA transcriptional expression,play an important role in the process of arsenic poisoning liver damage.? hOGGl gene polymorphism was closely related to liver damage by arsenic poisoning,but not observed hOGGl gene polymorphisms affect expression of mRNA transcription ? hOGG1 gene methylation may be affected by gene polymorphism a,it was participates in the development of liver injury of arsenic poisoning ? This study found that arsenic caused by oxidation and antioxidant imbalance,and caused by high hOGG1 methylation transcription induced by abnormal expression of enzymology,arsenic poisoning is a major cause of liver damage.