title: 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.
  
  
  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.
  
  
  CONCLUSIONS
  The interactions of certain unfavourable genetic mutations can contribute to the evolution of leukoaraiosis.
authors.affiliation: Department of Neurology and Neurophysiology Central Laboratory, Pándy Kálmán County Hospital, Gyula, Hungary. szolnoki99@hotmail.com
authors.forename: Z
authors.initials: Z
authors.lastname: Szolnoki
authors.forename: F
authors.initials: F
authors.lastname: Somogyvári
authors.forename: A
authors.initials: A
authors.lastname: Kondacs
authors.forename: M
authors.initials: M
authors.lastname: Szabó
authors.forename: L
authors.initials: L
authors.lastname: Fodor
authors.forename: J
authors.initials: J
authors.lastname: Bene
authors.forename: B
authors.initials: B
authors.lastname: Melegh
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D001921:Brain / Q000473:pathology; D004252:DNA Mutational Analysis; D015140:Dementia, Vascular / Q000175:diagnosis / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D010455:Peptides / Q000235:genetics*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D025941:Protein Interaction Mapping; D012016:Reference Values; D012306:Risk
chemical_list: D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D010455:Peptides; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D007703:Peptidyl-Dipeptidase A