Journal
JOURNAL OF MOLECULAR NEUROSCIENCE
Volume 27, Issue 1, Pages 23-27Publisher
HUMANA PRESS INC
DOI: 10.1385/JMN:27:1:023
Keywords
late-onset Alzheimer's disease; methylenetetrahydrofolate reductase (MTHFR); homocysteine; apolipoprotein E; polymorphism; Chinese
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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% Cl 1.85-17.72, and p = 0.002, OR = 1.89 95% Cl 1.25-2.86) were found. After stratifying by apolipoprotein E allele 4 (APOE epsilon 4) status, increased LOAD risks associated with the TT genotype only in the APOE 84 noncarriers (chi(2) = 8.92, df 1, p = 0.003) and with the T-allele in either group (chi(2) = 5.18, df = 1, p = 0.023 and chi(2) = 5.53, df 1, p = 0.019) were seen. These results suggest that as an APOE epsilon 4 allele-dependent risk factor, the MTHFR gene C677T polymorphism is involved in developing LOAD in Chinese.
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