The Study Of Association Between Catechol-O-Methyltransferase Gene Polymorphism(rs4680) And Obsessive–Compulsive Disorder

Objective:Several studies have shown that catecholamine-oxymethyltransferase(COMT)is a genetic component in the etiology of obsessive-compulsive disorder(OCD).As a functional single nucleotide polymorphism site,the activity of catecholamine oxymethyltransferase(COMT)rs4680 polymorphism on enzymes showed that it may affect the level of dopamine in the brain.To investigate the association between Catechol-O-Methyltransferase(COMT)gene polymorphism(rs4680)and obsessive-compulsive disorder(OCD).Methods:400 cases of obsessive-compulsive disorder and 459 health control subjects in Shandong Han population were studied,according to sex?onset age stratification.MassARRAY time-of-flight mass spectrometry(MALDI-TOF)technique was used to genotype COMT gene single nucleotide polymorphism(SNP)Sites rs4680.We compared the distribution frequency of allele and genotype in different groups.Then 400 cases of obsessive-compulsive disorder and 459 health control subjects were stratificated according to sex?onset age,the distribution frequency of allele and genotype in different groups were compared.Results:The genotype distribution of COMT rs4680 locus in obsessive-compulsive disorder group was in good agreement with the expected value(c~2=0.098,df=1,P=0.754),and that of COMT rs4680 locus in control group was in good agreement with the expected value(c~2=0.015,df=1,P=0.902);that of COMT rs4680 locus in male obsessive-compulsive disorder group was in good agreement with the expected value(c~2=0.015,df=1,P=0.902).The genotype of COMT rs4680 locus in the male control group was in good agreement with the expected value(c~2=0.058,df=1,P=0.810);the genotype of COMT rs4680 locus in the female obsessive-compulsive disorder group was in good agreement with the expected value(c~2=0.0416,df=1,P=0.83).The genotype observations of COMT rs4680 locus in the female control group were in good agreement with the expected values(c~2=0.558,df=1,P=0.455);the genotypie observations of COMT rs4680 locus in the early-onset obsessive-compulsive disorder group were in good agreement with the expected values(c~2=0.118,df=1,P=0.731),and that in the late-onset group were in good agreement(c~2=0.118,df=1,P=0.731).The results showed that the genotype distribution of each group conformed to Hardy-Weinberg's law of genetic equilibrium,and the coincidence was good,indicating that the sample selected in this study had good population representativeness.There was no significant difference in the distribution of COMT rs4680 allele(c~2=0.108,P=0.742)and genotype frequency(c~2=0.131,df=2,P=0.937)between OCD group and control group(P>0.05).There was no significant difference in the distribution of alleles(c~2=0.212,P=0.645)and genotype frequencies(c~2=0.258,df=2,P=0.879)of COMT rs4680 locus between the early-onset obsessive-compulsive disorder group and the control group(P>0.05).There was no significant difference in the distribution of COMT rs4680 allele(c~2=0.001,P=0.981)and genotype frequency(c~2=0.008,df=2,P=1.000)between the late-onset obsessive-compulsive disorder group and the control group(P>0.05).After sex stratification,there was no significant difference in the distribution of COMT rs4680allele(c~2=0.562,P=0.453)and genotype frequency(c~2=0.694,df=2,P=0.707)between the male obsessive-compulsive disorder group and the male control group(P>0.05).There was no significant difference in the distribution of COMT rs4680 alleles(c~2=0.168,P=0.682)and genotype frequencies(c~2=0.596,df=2,P=0.742)between the female obsessive-compulsive disorder group and the female control group(P>0.05).No allele at rs4680 locus was found to be a risk factor for OCD.Conclusions:The results of this study indicate that there may be no association between COMT Gene Polymorphism(rs4680)and obsessive-compulsive disorder in the Han population of Shandong.There are several functional single nucleotide polymorphisms(SNPs)in COMT,such as rs4680 and rs6269,and rs4680 is one of the most studied.In this study,only COMT rs4680 polymorphism is detected.Although no association is found between COMT rs4680 polymorphism and obsessive-compulsive disorder(OCD),it can not be concluded that COMT rs4680 polymorphism does not play an important role in the pathogenesis of OCD.This polymorphism may not play an independent role in the pathogenesis of OCD.Whether there are other polymorphic loci to participate in the susceptibility to obsessive-compulsive disorder needs further study.The correlation between COMT gene and obsessive-compulsive disorder needs to be further studied by enlarging the sample size,designing more rigorously and adding more polymorphic sites to ensure the homogeneity of the subjects.