Association Study Of Angiotensin-converting Enzyme Gene Gene Insertion/deletion Polymorphism With Schizophrenia And Its Clinical Phenotype

Background and Objective:Previous studies have explored the association between angiotensin-converting enzyme(ACE),ACE gene insertion/deletion(ACE I/D)polymorphisms and the susceptibility of schizophrenia.However,the results have been inconsistent.In addition,several studies have confirmed that this functional polymorphism might be related to the impairment of specific aspects of cognition.The purpose of this study was to investigate the association of ACE gene I/D polymorphism with chronic schizophrenia and its clinical phenotype in Chinese Han population.The current study aimed to provide some theoretical basis for the study of etiology,clinical symptoms,and pathological mechanism of cognitive impairment of schizophrenia from the perspective of genetics.Methods:In this study,a cross-sectional,case-control study was performed.A total of 751 patients with chronic schizophrenia who met the criteria were enrolled from two psychiatric hospitals according to the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition(DSM-?).At the same time,295 healthy controls in the surrounding areas of the hospital were enrolled.On the day of enrollment,general demographic,clinical and blood samples were collected.The polymerase chain reaction(PCR)was used to detect the ACE gene I/D polymorphism of all subjects.SHEsis online analysis software and SPSS 22.0 were used for statistical analysis.The distribution of allele and genotype frequencies were compared between patients with chronic schizophrenia and healthy controls.The differences in PANSS scale scores among patients with different genotypic subgroups were compared.A total of 550 patients and 283 controls in this study completed the Repeatable Battery for the Assessment of Neuropsychological Status(RBANS)assessment,comparing the cognitive function differences between the patients and the healthy controls;comparing the differences of two groups in cognitive function between different genotypic subgroups;comparing the difference in cognitive function between different genotypic subgroups within the patients and the controls,respectively;analyzing whether the five subscale scores and total score of RBANS are affected by the interaction effects of diagnosis X genotype;analyzing the influencing factors of positive indicators in cognitive assessment.Results:1.The genotypic distribution of the patients with chronic schizophrenia and the healthy controls was in line with H-W equilibrium(P>0.05).There was a significant difference in the allele and genotypic distribution frequency of the ACE gene I/D polymorphism between the two groups(P<0.05),carriers of D alleles(DD homozygotes and ID heterozygotes)had a 0.496 times higher risk than those in the ? homozygous group.The DD homozygous group had 1.035 times higher risk of disease than the ? homozygous group.The disease risk of the DD homozygous group was 0.592 times higher than the ID heterozygous group.2.Compared with ? homozygous patients,the depressive factor score of DD homozygous patients was significantly reduced(Bonferroni corrected P<0.05).3.The RBANS subscale scores and total score of patients with chronic schizophrenia were significantly lower than those of the healthy controls(P<0.0001)except for visuospatial(P>0.05).4.There was no significant difference between different genotypic subgroups of five subscale and total scores of RBANS in patients with chronic schizophrenia and healthy controls(P>0.05).The attention subscale score of the RBANS in male patients with ?homozygous was significantly lower than that of ID heterozygous(Bonferroni corrected P<0.05).The five subscale and total scores of RBANS had no significant difference among different genotypic subgroups within the healthy controls(P>0.05).Besides,there were no significant genotype X diagnosis effects on any of the RBANS subscale and total scores(P>0.05).Years of education(P<0.0001),age of hospitalization(P<0.0001),ACE genotype(P=0.008),and hospitalization times(P=0.025)have significant effects on the attention score of male patients with chronic schizophrenia.Conclusions:1.The ACE gene I/D polymorphism may be associated with the susceptibility to chronic schizophrenia;the D allele and DD genotype may be the risk factors for chronic schizophrenia in the Chinese Han population.2.ACE gene I/D polymorphism may be related to depressive symptoms in patients with chronic schizophrenia,? genotype may be a risk factor for severe depressive symptoms in patients with chronic schizophrenia.3.The cognitive function of patients with chronic schizophrenia is significantly decreased;there is a wide range of cognitive impairment involving immediate memory,language,attention,and delayed memory in patients with chronic schizophrenia.4.ACE gene I/D polymorphism may be associated with attention dysfunction in male patients with chronic schizophrenia,? homozygote may be a risk factor for attention dysfunction in male patients with chronic schizophrenia.