Cholecystokinin Gene -45C/T Polymorphism And The Research Of Its Relationship With Schizophrenia And With Depression, And Its Forensic Significance Introduction

IntroductionCholecystokinin(CCK)gene has polymorphisms, and has a close relationship with some human psychic diseases by influencing or changing the roles of other neurotransmitters on CNS. So, cholecystokinin gene can acts as a new forensic individual identification and parentage testing genetic marker or legal psychiatry testing referential genetic marker.Human CCK gene is mapped to 3q12.3. It has 3 exons and 2 introns. And it is about 7 kb. There are two polymorphism loci in the promoter region of the CCK gene, i.e.-196G/A and-45C/T. There hasn't been any association analysis report between the allelic frequency of-45C/T polymorphism and schizophrenia in our country up to now. Although some achievements have been obtained by foreign researchers, we can not use them directly for the mutation between different races and ethnics. To provide new genetic targets for the estimated of People's spiritual and physiological functions and some basic data for forensic application, this study used Bidirectional PCR Amplification of Specific Alleles technique to detect the genetic polymorphisms of-45C/T in the Han population, schizophrenia and depression population groups, and research the genetic association in these groups.Materials and methodsThe diagnoses of depression and schizophrenia were based on DSMⅢ-R and DSM-Ⅳrespectively. depression patients 94 cases consisted of 39 males and 55 females. Schizophrenic patients 207 cases consisted of 114 males and 93 females. Control subjects were healthy Han Chinese in northern China, They included 113 males and 89 females. For a total of 503 cases. Use Bidirectional PCR Amplification of Specific Alleles technical to amplify CCK gene promoter fragment which contains the site-45C/T polymorphism, through polyacrylamide gel electrophoresis, silver staining to detect PCR product and genotyping.ResultsIn 202 Chinese han individuals, we found two alleles and three genotypes: homozygote CC was 62 individuals, its frequency was 0.3069; heterozygote CT was 104 individuals, its frequency was 0.5149; homozygote TT was 36 individuals, its frequency was 0.1782. Allele C frequency was 0.5644; allele T frequency was 0.4356. All these genotypes data were accordant with the law of Hardy-Weinberg equilibrium.In 207 schizophrenia patients, homozygote CC was 51 individuals, its frequency was 0.2464; heterozygote CT was 109 individuals, its frequency was 0.5266; homozygote TT was 47 individuals, its frequency was 0.2270. Allele C frequency was 0.5097; allele T frequency was 0.4903. All these genotypes data were accordant with the law of Hardy-Weinberg equilibrium.In 94 depression patients, homozygote CC was 35 individuals, its frequency was 0.3723; heterozygote CT was 33 individuals, its frequency was 0.3511; homozygote TT was 26 individuals, its frequency was 0.2766. Allele C frequency was 0.5479; allele T frequency was 0.4521.When compared the genetic polymorphisms of-45C/T locus of healthy populations with those of depressive patients'and schizophrenia patients', we found that the P values were both less than 0.05.genotype frequency distribution differences in depression and normal control group, P values was less than 0.05. After three groups grouped by sex, schizophrenia by clinical subtype, a further division can be seen: Schizophrenia women, women of sub-type group, those who with family history and women of family history compared with the healthy populations, allele distribution P value was less than 0.05; those who with family history, women of sub-type group compared with the healthy populations' genotypes frequency, P value was less than 0.05.DiscussionAccording to the genotype and allele frequency in Chinese han data, we conclude that the DP value is 0.6089; the EPP value is 0.1854; PIC value is 0.3708; H value is 0.4929. This locus belongs to high discrimination power genetic systems. We can apply it to forensic individual identification and parentage testing.This study investigated the allele and genotype frequency of CCK gene-45C/T polymorph-ism in the Chinese Han, schizophrenia patients and depression patients. After Chi-statistical analysis, results showed that:1) compare the Chinese Han individual with the depression individual, there is significant difference in genotype frequencies (P<0.05), T/T and C/C genotype may be associated with depression。2)-45c/t locus T/T genotype and T allele in schizophrenia patients with family history was significantly higher than that of healthy ones, this is equally clear in female patients, but between different subtypes of schizophrenia there is no obvious difference. in the distribution. It demonstrates that T/T genotype and T allele may be a risk factors in positive family history and women schizophrenia.ConclusionCholecystokinin gene-45C/T locus has good genetic polymorphism in Han population of China, and provides the necessary data for forensic individual identification and parentage testing. Genotype C/T turn into homozygous may be possible risk factors for depression; T/T genotype and T allele may be a related genes of positive family history and women schizophrenia.