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Specific APO E genotypes in combination with the ACE D/D or MTHFR 677TT mutation yield an independent genetic risk of leukoaraiosis
Author(s) -
Szolnoki Z.,
Somogyvári F.,
Kondacs A.,
Szabó M.,
Fodor L.,
Bene J.,
Melegh B.
Publication year - 2004
Publication title -
acta neurologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.967
H-Index - 95
eISSN - 1600-0404
pISSN - 0001-6314
DOI - 10.1046/j.1600-0404.2003.00218.x
Subject(s) - methylenetetrahydrofolate reductase , leukoaraiosis , genotype , medicine , genetics , white matter , biology , endocrinology , magnetic resonance imaging , gene , radiology
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.

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