Lack Of Association Between COMTVal158Met Polymorphism And Late-onset Alzheimer’s Disease In Han Chinese

Objective: COMT(catechol-O-methyltransferase) is a key enzyme.It influences the dopamine degradation in prefrontal cortex and plays an important role in cognitive function impairment in the adults. A functional single nucleotide polymorphism(rs4680 SNP; G to A) in the COMT coding region causes Val158 Met amino acid substitution in the corresponding protein, with Val allele exhibiting markedly 3-to-4fold higher than Met in enzyme activity. Recent study reported that the functional rs4680 polymorphism within COMT gene was associated with susceptibility to AD in Caucasians. In order to examine the association between polymorphism in COMT gene and late-onset AD(LOAD) in a Han Chinese group, we analyzed the genotype and allele distributions of the COMT rs4680 polymorphism in a Han Chinese population.Methods: We employ case-control study method.1132 LOAD cases are choosen to conduct this experiment, while 1159 healthy people as the matched group. The COMT rs4680 SNP and Apo E gene were was genotyped using polymerase chain reaction–ligase detection reaction(PCR-LDR). Genotypes and alleles were compared using the chi-square test and logistic regression.Results: There is no significant association between the COMT rs4680 polymorphism and LOAD in the total sample. The genotypes were not significantly different from LOAD and controls. The frequency of the minor allele A was lower in Controls compared to LOAD(26.5% versus 28.0%). However, there was no significant differences between LOAD and controls. Therefore, our results showed that there was no statistically significant difference in COMT genotype and allele frequencies between the LOAD patients and healthy subjects. However, there was no even after statistical adjustment for age, gender and apolipoprotein E(APOE) status in the total sample as well as stratification for APOE status.Conclusions: The result of our experiment indicates that there is no significant association between the COMT rs4680 polymorphism and LOAD in the Han Chinese population. It is possible that the effect of COMT variation on AD risk is specific to particular ethnic groups or that the effect is not large enough to bedetected reliably by a cohort of our size. Future studies in more large cohorts and in other ethnic populations are needed to clarify the role of COMT polymorphisms in LOAD.