Association Study Of Gene Polymorphisms In MiRNAs Regulated Kininogen-L With Schizophrenia

Schizophrenia(SCZ)is a serious neuropsychiatric disease and one of the top 25mental illnesses in the world.Epidemiological studies have shown that schizophrenia affects approximately 1%of the general population and is more closely related to human morbidity,mortality,and the economic burden of individuals and society.So far,even though the exact pathogenesis of schizophrenia has not yet been determined,a large number of studies have confirmed that a variety of factors have led to the occurrence of mental illness,in which genetic factor is an important component,and individual differences in susceptibility to mental illness are largely due to genetic factor.Although there are many studies on the pathogenesis of schizophrenia from the epigenetic level,it is rare to study from the perspective of miRNA gene polymorphisms.The starting point of the study was the polymorphisms of miRNA genes which regulating the kininogen-L,we explored the relationship between miRNA gene polymorphisms that regulate kininogen L protein and schizophrenia.Purpose:To explore the relationship between miRNAs gene polymorphisms that regulate kininogen L protein and susceptibility to schizophrenia,and to analyze the interaction between miRNA gene polymorphisms on schizophrenia.Methods:In this study,a case-control study was conducted to select 513 patients with schizophrenia and 509 healthy controls.The bioinformatics method was used to predict the miRNAs gene polymorphisms of the kininogen L protein,and finally including rs56103835,rs6513496,rs6513497 and rs2986407.Genotyping was performed using imLDR multiple SNP typing technique;rank sum test and chi-square test were used to compare the distribution of clinical features of schizophrenia patients between males and females;Hardy-Weinberg equilibrium was tested by goodness-of-fit chi-square test;allele and genotype frequency distribution of case-control group were analyzed by chi-square test;SNPStats online software was used for genetic model analysis;GMDR software was used for interaction between miRNA gene and gene;Quanto software was used for calculating statistical power.Results:1.There are 513 patients with schizophrenia in this study,including 273 males(53.2%)and 240 females(46.8%).Among males and females,the distributions of pre-existing personality,influence delusion,jealous delusion,logical disorder and illusion delusional syndromewere significant different(P<0.05).However,there was no significant difference in the distribution of other clinical features between males and females(P>0.05).2.The balance test of the case-control group showed that there was no significant difference in age and gender distribution between the two groups(Z=-0.403,P=0.687;c~2=2.849,P=0.091).3.The Hardy-Weinberg equilibrium test showed that the rs2986407 did not meet the equilibrium law in the control group(P=0.040),while the rest loci of the control group and all the loci in the case group were meet the equilibrium law(P>0.05).4.Allele and genotype frequency distributions of has-miR-323b rs56103835,has-miR-646 rs6513497,has-miR-1343 rs2986407 and has-miR-646 rs6513496 were not significant different between the two groups(P>0.05).5.The optimal genetic model of has-miR-323b rs56103835 was dominant model,and the association between gene polymorphism and susceptibility to schizophrenia is statistically significant under this model(P=0.038).However,there was no association between the genetic polymorphisms of the other three loci and the susceptibility to schizophrenia(P>0.05).6.The results of gene-gene interaction analysis showed that the locus rs56103835 had a significant advantage,and the multi-factor model(rs56103835/rs2986407)was the best model,its equilibrium test accuracy and cross-validation consistency were the highest.However,this best model was not associated with the risk of schizophrenia(P=0.3770).7.Statistical power analysis showed that the all sites were less power in the recessive genetic model,but the power was higher in the dominant model and the log-additive model,and the power of the rs56103835 was 37.34%-99.99%.The power of rs6513497 was 19.3%-99.99%,the power of rs6513496 was 32.82%-99.99%,and the power of rs2986407 was 25.87%-99.99%.Conclusion:1.has-miR-323b rs56103835was associated with the genetic susceptibility to schizophrenia in the Han population of northern China.2.has-miR-646 rs6513497,has-miR-1343 rs2986407 and has-miR-646rs6513496 had no relationship with the susceptibility to schizophrenia in the Han population of northern China.3.miR-323brs56103835?has-miR-646 rs6513497?has-miR-1343 rs2986407?and has-miR-646 rs6513496 have no interaction with susceptibility to schizophrenia innorthernChinese Han population.