EPB41L4A and LEP Gene Polymorphisms Are Associated with Antipsychotic-induced QTc Interval Prolongation in Han Chinese

Abstract To identify the genetic factors related to antipsychotic-induced QTc interval prolongation (AIQTIP), we analyzed the associations between single nucleotide polymorphisms (SNPs) of candidate genes and quantitative traits of AIQTIP in a Han Chinese population. In total, we collected 112 hospitalized patients suffered from schizophrenia meeting the entry criteria, including 34 first-episode drug-naive patients (FENP). All patients were treated with a single atypical antipsychotic drug (AAPD) for 4 weeks. We analyzed the quantitative genetic association between 10 SNPs in 8 candidate genes and AIQTIP using PLINK software. After 4 weeks of treatment, QTc interval of all patients was significantly prolonged and QTc interval of female patients was significantly longer compared with baseline. Antipsychotics have different effects on the prolongation of QTc. Quetiapine had the most distinct effect on AIQTIP. In all subjects, we found a significant association between the EPB41L4A gene SNP rs7732687 and AIQTIP. In male patients, we also found a significant association between the EPB41L4A gene SNP rs7732687 and AIQTIP. In female patients, we found the LEP gene SNP rs7799039 was significantly associated with AIQTIP. Our results provide preliminary evidence to support the genetic role of EPB41L4A and LEP in AIQTIP.