The Mthfr 677t Allele May Influence the Severity and Biochemical Risk Factors of Alzheimer'Sdisease in an Egyptian Population

D Hewedi,N Elhawary

doi:10.1016/s0924-9338(15)30608-8

Abstract

Introduction and Objectives Methylenetetrahydrofolate reductase (MTHFR) 677CT 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. Aims The aim of this study was to determine the genotype and allele frequencies of the rs1801133 SNP and to evaluate the influence of genotype on risk and severity of disease in Egyptian patients with AD. 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.

Highlights

Alzheimer’s disease (AD, MIM 104300) is a major cause of disability in the elderly population
Homocysteine levels in blood plasma were measured with a fluorescence polarization assay (Abbott IMX Homocysteine Assay), and plasma vitamin B12 levels were measured by immunoassay
AD: Alzheimer’s disease, EAD: early-onset AD, LOAD: late-onset AD. aNo significant difference in genotype distributions between EAD and LOAD cases (P > 0.05). bNo significant difference in allele frequencies between EAD and LOAD cases (P > 0.05). cNo significant difference in genotypes between AD cases and controls (P > 0.05). dSignificant difference in the frequencies of the T alleles between AD cases and controls (OR = 2.22)

Summary

Introduction

Alzheimer’s disease (AD, MIM 104300) is a major cause of disability in the elderly population. It is the most common form of dementia, affecting 1 in 8 individuals older than 60 years of age [1]. Most AD cases are late in onset and are probably influenced by both genetic and environmental factors. In the late stage of AD, ventricular enlargement and shrinkage of the brain may be observed by magnetic resonance imaging. Some characteristic changes in the AD brain include neuronal loss in selected regions; intracellular neurofibrillary tangles in the neurons of the cerebral cortex and hippocampus; and neuritic plaques containing amyloids that may be further surrounded by dystrophic neurites, reactive astrocytes, and microglia [1]

Methods

Discussion

Conclusion