The MTHFR 677T allele may influence the severity and biochemical risk factors of Alzheimer's disease in an Egyptian population.
OBJECTIVE
We evaluated whether the methylenetetrahydrofolate reductase (MTHFR) 677C>T marker influences the risk and severity of Alzheimer's disease (AD) and whether AD is associated with homocysteine, vitamin B12, and cholesterol levels in Egypt.


METHODS
Forty-three Alzheimer's cases and 32 non-AD controls were genotyped for the 677C>T polymorphism. Clinical characteristics and levels of homocysteine, vitamin B12, and cholesterol were assessed.


RESULTS
No significant differences in the frequencies of the MTHFR alleles or genotypes between AD cases and controls (P = 0.14) were identified. The 677T mutant allele was significantly overrepresented in AD cases compared to controls (OR = 2.22; P = 0.03). The 677T/T frequency was three times higher in AD patients than in controls, which could increase plasma homocysteine levels. Severe cases of AD were the most frequent in patients with the T/T genotype (11.6%). The effect of the MTHFR polymorphism on the risk of AD may be independent of homocysteine, vitamin B12, or even cholesterol levels.


CONCLUSIONS
The MTHFR 677C>T polymorphism--especially the presence of one copy of the T allele--appears to confer a potential risk for the development of AD. The T/T genotype may contribute to hypercysteinemia as a sensitive marker.
Department of Medical Genetics, Faculty of Medicine, Umm Al-Qura University, P.O. Box 57543, Makkah 21955, Saudi Arabia ; Department of Molecular Genetics, Medical Genetics Center, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt.
Nasser Attia
NA
Elhawary
Doaa
D
Hewedi
Arwa
A
Arab
Salwa
S
Teama
Hassan
H
Shaibah
Mohammed Taher
MT
Tayeb
Neda
N
Bogari
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics*; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood; D004534:Egypt; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014805:Vitamin B 12 / Q000097:blood
D006710:Homocysteine; D002784:Cholesterol; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D014805:Vitamin B 12