Association of MTHFR gene polymorphism C677T with susceptibility to late-onset alzheimer’s disease

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 ɛ 4) status, increased LOAD risks associated with the TT genotype only in the APOE ɛ 4 noncarriers (χ 2 =8.92, df=1, p =0.003) and with the T-allele in either group (χ 2 =5.18, df=1, p =0.023 and χ 2 =5.53, df=1, p =0.019) were seen. These results suggest that as an APOE ɛ 4 allele-dependent risk factor, the MTHFR gene C677T polymorphism is involved in developing LOAD in Chinese.