Association Between Gen PRKCB1,NRAS And Depression

Objective:Depression is a common mental illness and patients suffer from severe disease burden.The pathogenesis of depression,however,is not clear.In recent years,accumulating evidences suggest that the mechanism of neural plasticity plays an important role in the pathogenesis and treatment of depression,among which the neurotrophic factors are of great importance in the process of neural plasticity.Documents have confirmed that the NRAS and PRKCB1 gene encoding proteins have an important function in the neurotrophic factors pathway as well as in the precursors’ modification.It is reported that genes polymorphisms may affect biological function.This present study aims to investigate the expressive differences of mRNA levels of NRAS and PRKCB1 in peripheral blood and the association of NRAS and PRKCB1 polymorphisms(NRAS: rs12128420;PRKCB1:rs11859534;rs3785383;rs1490754;rs8054767)with the morbidity and symptom of depression.Methods:1.Firstly,31 depression patients who are either in drug na?ve period or drug washout period and 23 healthy control specimens were enrolled in this present study.Then,Taqman probe method was carried out to detect the mRNA expression patterns of NRAS and PRKCB1 in peripheral blood.2.A case-control study was applied in this study,according to the diagnostic criteria ofmajor depression of 《Diagnostic and Statistical Manual of Mental Disorders IV》,a total of 671(including 251 male and 420 female)depression patients for case group and709(including 331 male and 329 female)normal controls for control group in a HanChinese population were recruited.All of the subjects were recruited from department of outpatient and inpatient of Shanghai mental health center.There was no significant difference in age and gender between the two groups(p>0.05).3.HAMD-17 and HAMA-14 disease severity assessment were performed in all patients enrolled in the group.3ml venous blood samples were collected into tube for EDTA anticoagulation and kept at-20℃ after centrifugation.DNA was extracted by using 1ml blood genome DNA small extraction kit produced by Shanghai Lifefeng Biotech Co.,Ltd.NRAS(rs12128420),PRKCB1(rs11859534;rs3785383;rs1490754;rs8054767)polymorphism were genotyped by Taqman fluorescence quantitative polymerase chain reaction(PCR)technology.4.SHEsis online software was applied to carry out Hardy-Weinderg equilibrium and allelic association analysis.Choosing 19.0 for windows software SPSS for data processing.Quantitative data using independent sample t-test;chi-square test was used to compare the two groups or threegroups genotypes and alleles frequency.It was significantly difference if P<0.05.Results:There were 31 depression patients who are either in drug na?ve period or in drug washout period enrolled in this study.Among them,these depression patients included 16 males(52%)and 15 females(48%),with an average age 30.83±8.84 years old.There were 12 males(52%)and 11 females(48%),with an average age 28.52±5.12 yeare old.Our research found that the mRNA expression level of NRAS and PRKCB1 in peripheral blood was dramatically increased.The age in 674 case group(including 251 males,420 females)was between 18 and 65 years,the average age was 34.3±14.162 years old.The average age in 709 control group(including 331 males,329 females)was 34.18±17.67 years old.There was no significant difference in age and gender between case control group(p>0.05).For all the subjects,the genotypes of the 5 SNPs were in Hardy-Weinberg equilibrium(p>0.05).Regarding to genotypes and allele frequencies of rs12128420,rs11859534,rs3785383,rs1490754,rs8054767,no significant difference was found between depression patients and control subjects(p>0.05).The association between 5 SNPs and HAMD-17,HAMD-14 scale factors were analysed by variance analysis.The results showed that the 15 th item of HAMD-17 scale factor and 9th item of HAMA-14 scale factor were significantly different among each genotypes of rs12128420.The 12 th item of HAMD-17 scale factor was significantly different among the three genotypes of rs11859534.The 8th item of HAMD-17 scale factor was significantly different among the three genotypes of rs3785383.The 3rd,6th,14 th items of HAMD-17 scale factors and 6th item of HAMA-14 were significantly different among the three genotypes of rs1490754.The results showed that the 15 th item of HAMD-17 scale factor and 9th,11 th items of HAMA-14 scale factors were significantly different among the three genotypes of rs8054767.Conclusions:1.Our studies showed that mRNA expression levels was dramatically in NARS and PRKCB1.2.There were no evidence to prove there have association between the rs12128420,rs11859534,rs3785383,rs1490754,rs8054767 and major depression.3.There were associations between the 5 SNPs of NRAS and PRKCB1 and depression patients with gastrointestinal symptoms,early wakening,cardiovascular system symptoms,hypochondriasis,bradykinesia.