Specific APO E genotypes in combination with the ACE D/D or MTHFR 677TT mutation yield an independent genetic risk of leukoaraiosis.

Abstract

OBJECTIVE:

Ischaemic demyelination of the white matter of the brain is a frequent clinical entity. In the neuroimaging terms, it is referred to as leukoaraiosis. We earlier found that the co-occurrence of the homozygous methylenetetrahydrofolate reductase (MTHFR) 677TT and angiotensin-converting enzyme D/D (ACE D/D) genotypes yielded a highly significant moderate risk of leukoaraiosis. On the assumption of further genetic interactions, we have now investigated whether the different apolipoprotein E (APO E) genotypes, in pairwise combinations with the MTHFR 677TT or ACE D/D mutation, could lead to an increased risk of leukoaraiosis.

MATERIAL AND METHODS:

We analysed the occurrence of the APO E genotypes in pairwise combinations with the MTHFR 677TT or ACE D/D mutation in 315 consecutive Caucasian patients with leukoaraiosis. A total of 646 neuroimaging-free subjects acted as a control group.

RESULTS:

The APO E 2/2 and 2/3 or APO E 4/4 and 4/3 genotypes in combination with the MTHFR 677TT or ACE D/D mutation exhibited independent genetic risks of leukoaraiosis.

CONCLUSION:

The interactions of certain unfavourable genetic mutations can contribute to the evolution of leukoaraiosis.

• Authors: Z Szolnoki, F Somogyvári, A Kondacs, M Szabó, L Fodor, J Bene, B Melegh
• Journal: Acta neurologica Scandinavica (Acta Neurol Scand) Vol. 109 Issue 3 Pg. 222-7 (Mar 2004) ISSN: 0001-6314 [Print] Denmark
• PMID: 14763962 (Publication Type: Journal Article)

Chemical References

• Apolipoprotein E2
• Apolipoprotein E3
• Apolipoprotein E4
• Apolipoproteins E
• Peptides
• Methylenetetrahydrofolate Reductase (NADPH2)
• Peptidyl-Dipeptidase A

Topics

• Adult
• Aged
• Aged, 80 and over
• Apolipoprotein E2
• Apolipoprotein E3
• Apolipoprotein E4
• Apolipoproteins E (genetics)
• Brain (pathology)
• DNA Mutational Analysis
• Dementia, Vascular (diagnosis, genetics)
• Genetic Predisposition to Disease (genetics)
• Genotype
• Homozygote
• Humans
• Magnetic Resonance Imaging
• Methylenetetrahydrofolate Reductase (NADPH2) (genetics)
• Middle Aged
• Peptides (genetics)
• Peptidyl-Dipeptidase A (genetics)
• Polymorphism, Genetic (genetics)
• Protein Interaction Mapping
• Reference Values
• Risk