Effect Of GSTM1 And GSTT1 Deficiency On Haze-induced Acute Cardiovascular Effect

ObjectivesThe relationship between short-term exposure of air pollutants and changes in levels of autonomic nervous function and inflammation,oxidative stress,and monocytes-platelet activation biomarkers.MethodWe recruited 74 university student volunteers at Xinxiang Medical College.Meanwhile,the GST gene?GSTT1 and GSTM1?null polymorphisms were examined.According to the panel study design,the subjects were followed up six times from September to December of 2017.The subjects'heart rate?HR?,systolic blood pressure?SBP?,diastolic blood pressure?DBP?,mean arterial pressure?MABP?,and pulse were measured.Pressure?PP?,C-reactive protein?CRP?,8-hydroxydeoxyguanosine?8-OHdG?,tissue plasminogen activator?t-PA?and platelet-monocyte aggregation?PMAs?levels.Use the weather station of Xinxiang Medical College to record a variety of hourly air pollutants and meteorological data 1-7 days before each follow-up(PM_2.5?aerodynamic diameter?2.5?m?,PM₁₀?aerodynamic diameter?10?m?,ozone?O₃?,sulfur dioxide?SO₂?,nitric oxide?NO?,nitrogen oxides?NO_X?,carbon mono_Xide?CO?concentrations,temperature?T?,and relative humidity?RH?.A linear mixed-effects model was used to assess the relationship between air pollutants and cardiovascular indicators in single-pollutant and double-pollutant models controlling the effects of age,gender,body mass index?BMI?,date of detection?DOS,SDOS?,day of week?DOW?,temperature,and humidity.According to the GSTM1,GSTT1null polymorphism,the subjects were divided into eight groups:GSTM1+,GSTM1-,GSTT1+,GSTT1-,GSTM1+GSTT1+,GSTM1-GSTT1-,GSTM1+GSTT1-,GSTM1-GSTM1+.Then use single-pollutant model to analysis air pollutant-cardiovascular effects respectively.Result?1?Heart Rate?HR?PM₁₀?lags1?,and SO₂?lags1-2?are positively correlated with HR.In gene stratification analysis,PM₁₀,CO in the GSTT1-group,SO₂,NO,and NO_X in the GSTT1-,GSTM1+GSTT1-group were significantly positively correlated with HR.GSTM1+had no significant effect on HR.?2?Blood pressureThe average moving concentration of air pollutants in most lag days was negatively correlated with SBP,DBP,and MABP.In gene stratification analysis,except for the GSTM1-group of PM_2.5,negative associations between pollutants and and SBP,DBP in the gene null group?GSTM1-,GSTT1-,GSTM1-GSTT1-?were weakened or lost statistical significance compared with the gene expression group.No association was found between pollutants and PP.In gene stratification analysis,NO,NO_X were positively correlated with PP in the GSTM1-GSTT1-group with statistical significance.?3?C-reactive protein?CRP?There was a significant positive correlation between PM_2.5 in lags1-7 and CRP,but there was no correlation between other pollutants and CRP.In gene stratification analysis,PM_2.5-CRP was statistically significant in the GSTM1+,GSTT1-,GSTM1-GSTT1-and GSTM1+GSTT1-groups.There was a statistically significant negative relationship between CRP and PM₁₀,CO in the GSTM1+GSTT1+group.?4?8-Hydroxydeoxyguanosine?8-OHdG?There was a positive correlation between 8-OHdG and O₃?lags3?and a negative correlation with SO₂?lags3?.In gene stratification analysis,statistical significance was observed in the GSTM1-group of PM_2.5 and in the GSTM1-,GSTT1-,and GSTM1-GSTT1+groups of O₃.?5?Tissue plasminogen activator?t-PA?In early lags,there was a significant negative correlation between PM_2.5,O₃ and t-PA,and a positive correlation with PM10,CO,SO2,NO,and NOX.In gene stratification analysis,the relationship between each pollutant and t-PA in different genotype groups was similar to that of the single pollutant model,but lost statistical significance in the GSTT1-group.?6?Platelet-Monocyte Aggregation?PMAs?There is a positive correlation between PM_2.5?lags2-3?,PM₁₀?lags1-2?,CO?lag1?,NO?lag4?,and NO_X?lag4?and MPAs,and a negative correlation between O₃?lags4?and MPAs.There is a positive correlation in GSTM1+,GSTT1-group of PM_2.5,in GSTT1-,GSTM1+GSTT1-group of PM10 and CO,in GSTM1-group of NO,in GSTM1-,GSTM1+GSTT1-group of NO_X,and a negative correlation in GSTM1-,GSTT1–,GSTM1-GSTT1-group of O3.?7?Two pollutions ModelAdjustment for the second pollutant,the following pollutant-effect correlation remain-ned stable:O₃ and DBP,PM_2.5 and CRP,O₃ and 8-OHdG,O₃,CO and t-PA,PM_2.5and MPAs.Conclusion1 Air pollutants can reduce the SBP and DBP,but have less influence on PP;PM_2.5 can significantly increase CRP,causing systemic inflammation;O₃ significantly increased8-OHdG levels,inducing oxidative stress;O₃ significantly reduced t-PA activity,and CO increased t-PA activity,then affected fibrinolytic function;PM_2.5,PM₁₀,CO,NO,NO_X can significantly increase MPAs.2 GSTM1 and GSTT1 genes null enhance the correlation between air pollutants and acute cardiovascular effect,and has a combined effect between GSTM1 and GSTT1.