Correlation Between Variants Of The CREB1 And GRM7 Genes And Risk Of Depression

Research background and purpose:Depression,a complex and common mental disease,is characterized by depression,loss of interest,and even suicidal tendencies.With the continuous understanding of depression and the fear of its high suicide rate,researchers have paid more attention to depression and deepened their research on depression.Unfortunately,the pathogenesis of depression is still unclear.According to the current research,depression is the result of the joint action of environmental,genetic,endocrine and other factors.Single nucleotide polymorphism(SNP)refers to the change of a single nucleotide base at a certain position on the genome level,resulting in the allele variation of the position in the same body or the gene variation between different individuals.Using SNP as a genetic information marker to find the genetic risk factors of diseases and to find SNP sites on DNA sequences related to complex diseases is one of the important ways to understand the etiology and pathogenesis of complex diseases.CAMP-response element binding protein 1(CREB1)is a transcription factor that affects the expression of neurons;Metabolic glutamate receptor 7(GRM7)regulates cell metabolism through G-protein coupling.The pathogenesis of depression involves CREB1 and GRM7.Its gene polymorphism may affect the susceptibility of depression.This study selected two SNP sites of CREB1 gene(rs2253206 and rs10932201)and one SNP site of GRM7 gene(rs162209)to verify the correlation between rs2253206,rs10932201 in CREB1 and rs162209 in GRM7 and depression through comparative analysis of the SNP of depressed patients and healthy people,and to explore whether it is related to the degree of depression,whether it is the first onset and the risk of suicide.Materials and Methods:480 patients with depression who were treated in Jining Mental Hospital and Sichuan Provincial People’s Hospital from March 2018 to December 2019 were selected for clinical data collection such as general data and pathological characteristics.329 healthy volunteers who had no mental disease in the hospital physical examination during the same period served as the control group.Peripheral blood samples were collected and DNA was extracted,and rs2253206,rs10932201 and rs162209 were genotyped by restriction fragment length polymorphism polymerase chain reaction(PCR-RFLP)and Next-generation sequencing.The correlation between rs2253206,rs10932201 and rs162209 gene SNPs and depression in 479 patients with depression and 329 normal controls was analyzed using different models,and the correlation between rs10932201,rs2253206 and rs162209 gene polymorphisms and the degree of depression,whether it is the first attack and the risk of suicide was stratified.Result:1.In the codominant model,there was a significant difference in the distribution of rs2253206 SNP site AA genotype between the depression group and the control group.The frequency of rs2253206 SNP site AA genotype in the depression group was 11.9%,which was significantly higher than that in the control group(6.7%).OR=2.00,95%CI was 1.15-3.49,and the P value was 0.01,which had statistical significance.In the recessive model,the distribution of rs2253206 SNP site AA genotype also showed significant difference between depressed patients and control group.The OR value was1.93,95%CI was 1.13-3.29,and P value was 0.01,showing significant statistical difference.The A allele distribution of rs2253206 SNP sites in depression group also tended to be higher than that in control group(OR=1.25,95%CI=1.00-1.56,P=0.05).2.In patients with depression,the distribution of GA genotype in the codominant model of rs10932201 SNP site was significantly different from that in the control group.The frequency of GA genotype at rs10932201 SNP site in patients with depression was 52.5%,which was significantly higher than that at 37.2% in the control group.The OR value was1.81,95%CI was 1.27-2.58,and P value was 0.001.In the dominant model,GA/GG genotype frequency in rs10932201 SNP site depression group was significantly higher than that in the control group,with an OR value of 0.74,95%CI was 0.52-1.04,and P value of 0.002,showing a significant statistical difference.The frequency of rs10932201 SNP site G allele in depression group was 36.7%,which was higher than that in control group(28.9%)(OR=1.29,95%CI=1.01-1.65,P=0.04).3.Correlation analysis of rs162209 polymorphism of GRM7 gene and risk of depression showed no correlation between rs162209 SNP and risk of depression.4.When data on several disease-related variables were stratified,none of the three gene SNPS was associated with depression,first onset,or suicidal tendencies.Conclusion:1.CREB1 gene rs2253206 and rs10932201 may be related to the occurrence of depression.2.There is no correlation between rs162209 SNP and depression risk.3.The polymorphisms of CREB1 gene rs2253206 and rs10932201 and GRM7 gene rs162209 were not found to be correlated with the degree of depression,first onset or suicidal tendency.