Correlation Between Antipsychotics-induced QT Interval Prolongation And BDNF Gene Polymorphisms

Objective:Antipsychotic drugs(APD)is the main clinical therapy for patients with schizophrenia(SCH).But compared with typical antipsychotics(TAPs),atypical antipsychotics(AAPs)have more likely to cause some adverse reactions,such as weight gain(AIWG),abnormal metabolisms of glucose and lipid,QT interval prolongation(QTIP),greatly increased torsades de pointes(TdP),and even the risk of sudden cardiac death(SCD).Therefore,ADP increases the mortality in patients with SCH.The adverse effects of ADP-induced QT interval prolongation(AIQTIP)have become a hot topic of clinical and scientific research.There are many factors influencing AIQTIP,among them,genetic factors play a very important role in the pathogenesis.Brain derived neurotrophic factor(BDNF)has certain effects on the abnormal lipid metabolism and the blocking of potassium channels.There is a correlation between the abnormal lipid metabolism and the blocking of potassium channels and QTIP.Therefore,the BDNF gene may be involved in the process of AIQTIP.The purpose of this study was to explore the correlation between BDNF gene polymorphisms and the AIQTIP,in order to further explore its related mechanism,and to provide a new basis for the use of APD in patients with SCH.Methods:258 patients with SCH treated by a single APD(Olanzapine(Ola),Risperidone(Ris),Quetiapine(Que))were enrolled in Tianjin Anding Hospital from January 2014 to January 2016 according to the inclusion criteria and exclusion criteria.The subjects were observed 4 weeks.At the baseline and after 4 weeks' treatment,electrocardiogram(ECG)was detected.Heart rate,QRS wave,PR interval period and QT interphase were recorded.Height and weight were measured.Triglycerides(TG),High density lipoprotein cholesterol(HDL),Low density lipoprotein cholesterol(LDL),Cholesterol(CHOL),Glucose(GLU)were detected.In addition,5ml peripheral was extracted.DNA was extracted by high salt method.A further genotyping of the gene locus of the candidate gene BDNF(rs6265)was carried out by using the Matrix-Assisted Laser Desorption Ionization Time-Of-Flight Mass Spectrometry(MALDI-TOF-MS).Data were collated and analyzed with SPSS22.0.Categorical data by chi-square test;measurement data using t test,different groups using independent sample t test,data in the group with paired t test,more than two groups of data using analysis of variance;Spearman correlation analysis was used for correlation analysis,and P<0.05 was considered statistically significant.Results:1.All patients after receiving APD,the variations of Heart rate,PR,QTc interphase,TG,HDL and LDL,GLU,weight,BMI were all significant at baseline and after 4 weeks' treatment(P<0.05).2.No matter male patients or female patients,after receiving APD,the values of QTc interphase,TG,HDL,GLU,weight,BMI all have significant difference between baseline and after 4 weeks' treatment,(P<0.05).The values of heart rate,LDL and CHOL of women in different detecting time also have a significant difference(P<0.05).3.Whether patients with first-episode SCH or not,after receiving APD,the values of heart rate,QTc,TG,weight,BMI between baseline and 4 weeks all have significant differences(P<0.05);In addition,the value of LDL in first-episode group and the values of PR,HDL and GLU in the other group,also showed significant differences in different detection time(P<0.05).4.Regardless of Ola,Ris and Que group,after the treatment,the values of QTc,TG,weight,BMI between baseline and after 4 weeks' treatment,all have significant differences(P<0.05);In addition,patients treated with Ola,the values of PR,LDL,CHOL showed significant difference in different detection time(P<0.05).In patients treated with Ris,the variations of the heart rate,HDL and GLU were significantly in different detection time(P<0.05).The value of HDL patients treated with Que had significant difference in different detection time(P<0.05).AIQTIP was significantly correlated with baseline PR wave in all patients and Ola groups(P<0.05,r=0.12;P<0.05,r = 0.21)5.After accepting APD,theQTc,TG,HDL,weight,BMI between baseline and after 4 weeks' treatment all have significant differences in C T,C C,T T groups(P<0.05);In addition,the values of heart rate,LDL and GLU of patients in group C C were significantly different in different detection times(P<0.05).The values of LDL and GLU in group C C were also significantly different in different detection times(P<0.05).6.After accepting APD,the variations of QTc in three groups were statistically significant(P<0.05),and the variations of QTc in C C group is more obvious than in other two groups.Conclusion:1.BDNF gene locus rs6265 was significantly correlated with the variations of QTc,and the differences in the value of QTc in the three groups were statistically significant(P<0.05).The increase of QTc in patients with C C genotype was significantly higher than those in the other two groups.2.In the use of Ola,Ris and Que groups,different APD will affect the QT interval in different degrees.3.In the whole population,baseline PR was positively correlated with QTIP,indicating that it may be a predictor of the QTIP.