| Background and Objective:Schizophrenia (SZ) is a common kind of serious mental disease, which is often involved in various disorders (emotion, thinking, awareness, behavior, etc.) and discordance of mental activities. SZ is characterized by irritability, reduced impulse control, sensitive and suspicious behaviors clinically; discordance of thinking, emotion, and social behaviors; uncommunicative and eccentric temperament with decreased social function; delusion, poverty of thought, apathy, etc. Among the inpatients in psychiatric hospital, SZ patients accounted for80%～90%of the total number. A large number of studies have shown that SZ is closely related to genetic factors, but the genetic model of the disease is not in conformity with the Mendelian inheritance law. SZ belongs to the complex genetic diseases, with the heritability is larger than70%.At present, there are three main aspects of SZ pathogenesis in neural biochemical level:dopamine hypothesis, serotonin hypothesis and glutamate hypothesis. In addition, SZ may also be related to the changes of other neurotransmitter systems, such as gamma-aminobutyric acid (GABA), neuropeptide, acetylcholine, adrenaline, and the second messengers or the interactions between these systems. Plenty of evidence suggests that endocannabinoids system changes in SZ patients, and the dysfunction of the system has a very close relation with the incidence of SZ. Currently, the study of the system mainly concentrated in the cannabinoid receptor1(CB1R). Cannabinoid receptor1is the polypeptide composed of473amino acid encoded by CNR1genes. It belongs to the inhibitory G protein coupled receptor family. At present, though there are many researches on CNR1gene of foreign, the results are different. There has not seen any domestic research about the relationship between CNR1gene polymorphism and SZ in China. So,we choose the CNR1gene as the object of study.In order to further explore the relationship between CNR1gene polymorphism and SZ, a total of three polymorphism site (including2site (rs1049353, rs12720071) on the exon4and1site(rs9450898) on the intron2) were selected. And the genotype and allele frequency of the three site in Henan Han population were detected through by PCR-RFLP. And the haplotype analysis was used to evaluate the influences of this gene and the three site on SZ in Henan Han nationality, thus providing a certain molecular biological basis for the onset of SZ.Research object:351cases of SZ patients (male:183cases; female:168cases) were selected in this paper, who had been admitted in Zhengzhou Mental Disease Prevention and Control Hospital, the average age was34.9±12.0years old. The control group selected385random individuals (male:238cases; female:147cases) from the healthy physical examination. The average age was35.5±11.0years old. There was no genetic relationship among the individuals, all of which were Henan Han nationality. In this study, patients or their guardians and the normal control health people are all informed consent.Research methods:RFLP-PCR method was adopted in the research.1) To extract the Sample DNA to detect the purity and concentration of DNA;2) To design and synthesize the primers;3) PCR amplification and enzyme digestion;4) Electrophoresis and sequencing. SHEsis online statistical software was used for the Hardy-Weinberg balance inspection on the selected patients and the normal control group, and haplotype analysis and linkage disequilibrium inspection were performed on the three polymorphism loci; SPSS17.0was used for statistical analysis, and chi-square test was adopted for the allele frequency on three polymorphism site and on the differences of genotype frequency distribution. Relative risk of polymorphism site on SZ was estimated. And the inspection level was a=0.05.Results:1. There were statistically significant difference of the C/T allele frequency and frequency distribution of the three genotypes (CC, CT and TT) on rs9450898in CNR1gene between the two groups(P=0.012;P=0.044).Under dominant mode, the difference of distribution of CC and CT/TT genotype frequency on rs9450898in CNR1between the two groups was statistically significant(P=0.013); under the addictive mode, the difference of distribution of CT genotype frequency between the two groups was significant(P=0.018); while under the recessive mode, the difference of genotype frequency distribution on this site between the two groups was not significant(P>0.05). The differences on rs1049353G/A and rs12720071A/G allele frequency and genotype distribution between groups were not statistically significant, and the analyses under different inheritance modes also show no difference(P>0.05).2. Gender stratification analysis results showed that among the male group, differences of C/T allele frequency on rs9450898in CNR1gene and of the genotype frequency between the groups were statistically significant(P=0.008, P=0.021). And there were no statistically significant differences of the allele frequency on rs1049353and rs12720071and of the distribution of genotype frequency between the two groups(P>0.05); among the female group, allele frequency of the three polymorphism site of CNR1gene and distribution of genotype frequency were not statistically significant different(P>0.05).3. Haplotype analysis showed that distribution frequency of T-G-A haplotype in patients group was obviously lower than the control group(P=0.040).Conclusions1. CNR1gene rs9450898and the occurrence of schizophrenia in Henan Han population has some relevance, the one who carries T allele (or CT/TT) will reduce the risk of the occurrence of schizophrenia. T allele play a protective role, and this protective effect in males is more obvious.2.In the rs9450898,rs1049353and rs12720071, the T-G-A haplotype was negatively correlated with the incidence of schizophrenia in Henan Han population, and will reduce the risk of the occurrence of schizophrenia, it is a protective haplotype. |
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