A Preliminary Study On The Relationship Between Ziprasidone-induced Drowsiness And H₁ Receptor Gene Polymorphism

Objective and Significance:Through the detection of histamine H₁ receptor gene（Histamine H₁ receptor,HRH₁）rs901865,rs1552498,rs17034063 locus genotype and allele distribution in the population around Xi’an,in order to study the sleepiness caused by ziprasidone and histamine H₁receptor according to the analysis results,the reliability of using this biomarker to predict drowsiness is proved,so as to guide patients’clinical precision medication.Methods:The study included 71 male patients who were hospitalized in Xi’an Mental Health Center and were diagnosed with schizophrenia from May 2020 to January 2021（all met the inclusion criteria）.The Epworth Sleeping Scale（ESS）scoring standard divides the above-mentioned patients into a sleepiness group and a non-sleepiness group.First,through the case-control method and molecular experiment technology,the clinical information and laboratory indicators of the two groups were collected.Then,the peripheral venous blood drawn from the patient’s elbow is used for polymerase chain reaction（PCR）and gene sequencing to detect the polymorphisms of histamine H₁ receptor genes at rs901865,rs1552498,and rs17034063.Then,the clinical information,laboratory indicators,histamine H₁ receptor gene each site genotype,allele frequency distribution of the two groups were analyzed.Finally,reveal the relationship between ziprasidone-induced sleepiness and H₁receptor gene polymorphism.Results:1.Clinical data and laboratory indicators:The age,height,weight,body mass index（BMI）between the two groups,as well as the ESS score before and after the medication,and after the medication（1 hour,2 hours,3 hours,4 hours,5 hours and 6 hours）blood drug concentrations are compared.The experimental results showed that the ESS scores between the two groups after taking the drug were statistically significant（P<0.05）,and the other indicators were not statistically significant（P>0.05）.2.Genotype and allele frequency:First,after the Hardy-Weinberg balance test,the P values at each point of the included cases were all greater than 0.05.Then,the two groups of HRH₁ rs901865 and rs17034063 locus genotype,allele frequency distribution were compared,the P value is less than 0.05,the difference was statistically significant;the two groups of HRH₁ rs1552498 locus genotype,allele frequency was compared,P values were all greater than 0.05,the difference was not statistically significant.3.Genotypes and laboratory indicators:There was no significant difference between he genotypes of HRH₁ rs901865 locus and any laboratory indicators（P>0.05）.There was a significant difference between homocysteine（HCY）and HRH₁ rs1552498 locus genotypes（P<0.05）.Platelet count（PLT）and HRH₁ rs17034063 locus between the genotypes were significantly different（P<0.05）.4.Genotype and the potential risk of somnolence:There were statistically significant differences between CT and CC genotype and risk of sleepiness at HRH₁ rs901865 locus（P<0.05）.There was no significant difference between the genotypes of HRH₁ rs1552498 and the risk of sleepiness（P>0.05）.There were statistically significant differences between the genotypes of HRH₁ rs17034063 and the risk of sleepiness（P<0.05）.Conclusion:1.There was no significant difference in general clinical data of the study population,but there was significant difference in ESS score after administration.2.The polymorphisms at rs901865 and rs17034063 of HRH₁ gene are related to the sleepiness caused by ziprasidone.In the rs901865 locus of the HRH₁ gene,the CT genotype has a lower risk of drowsiness than the CC genotype;in the rs17034063 locus of the HRH₁gene,the CT+TT genotype has a higher risk of drowsiness than the CC genotype.The polymorphism at rs1552498 locus of HRH₁ gene is not correlated with sleepiness caused by ziprasidone.3.There is no correlation between the genotype of HRH₁ rs901865 locus and the experimental indexes.Homocysteine is different between the GG genotype at HRH₁rs1552498 and the AA+AG gene,and the platelet count is different between the CC genotype at HRH₁ rs17034063 and the CT+TT genotype.Therefore,rs901865 and rs17034063 polymorphisms of histamine H₁ receptor genes may be biomarkers for predicting the risk of sleepiness induced by ziprasidone.