title: Association of MTHFR gene polymorphism C677T with susceptibility to late-onset Alzheimer's disease.
abstract: Increased total plasma homocysteine (t-Hcy) levels are found to be associated with Alzheimer's disease (AD). Because the methylenetetrahydrofolate reductase (MTHFR) gene encodes a key enzyme that influences the metabolism of homocysteine, it has been considered as a possible genetic risk factor for AD. Although the MTHFR gene C677T polymorphism has a significant impact on reducing enzyme activity and increasing t-Hcy concentrations, the association between the C677T polymorphism and AD remains inconclusive. To determine whether the MTHFR gene C677T polymorphism contributes to the risk for late-onset AD (LOAD) in Chinese, we have investigated 104 sporadic LOAD patients and 130 healthy controls. The strong associations of the TT genotype and T-allele with LOAD (p 0.001, OR 5.73 95% CI 1.85-17.72, and p 0.002, OR 1.89 95% CI 1.25-2.86) were found. After stratifying by apolipoprotein E allele 4 (APOE epsilon4) status, increased LOAD risks associated with the TT genotype only in the APOE epsilon4 noncarriers (chi2=8.92, df=1, p=0.003) and with the T-allele in either group (chi2=5.18, df=1, p=0.023 and chi2=5.53, df=1, p=0.019) were seen. These results suggest that as an APOE epsilon4 allele-dependent risk factor, the MTHFR gene C677T polymorphism is involved in developing LOAD in Chinese.
authors.affiliation: Center for Human and Animal Genetics, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Binbin
authors.initials: B
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Jin
authors.forename: Rui
authors.initials: R
authors.lastname: Kan
authors.forename: Shun
authors.initials: S
authors.lastname: Ji
authors.forename: Chuanfang
authors.initials: C
authors.lastname: Zhang
authors.forename: Zeping
authors.initials: Z
authors.lastname: Lu
authors.forename: Chenguang
authors.initials: C
authors.lastname: Zheng
authors.forename: Ze
authors.initials: Z
authors.lastname: Yang
authors.forename: Li
authors.initials: L
authors.lastname: Wang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2)