Evaluation of the roles of common genetic mutations in leukoaraiosis

Objectives - Leukoaraiosis, a relatively frequent neuroimaging entity, is p resumed to be primarily a vascular problem. However, it can be explained on ly in part by vascular risk factors. With the assumption of genetic suscept ibility, the roles of common genetic polymorphisms and mutations in leukoar aiosis were examined in this study. Material and methods - A detailed clini cal scrutiny of 843 Hungarian neurological patients with mild cognitive-lik e complaints revealed 229 subjects with leukoaraiosis that was probably vas cular in origin: 143 with leukoaraiosis alone (group 1), and 86 with leukoa raiosis plus cerebral infarction (group 2). In all 229 patients, the methyl enetetrahydrofolate reductase C677T (MTHFR C677T) mutation and angiotensin- converting enzyme (ACE I/D) polymorphism were examined by means of the PCR technique. The prevalences of the different genotypes for the examined muta tions in the 2 groups were analysed in comparison with the data on 362 neur oimaging alteration-free subjects as controls. Results - The ACE D/D genoty pe (38.37%, P < 0.0005; OR 2.46, 95% CI, 1.49-4.08) and ACE D allele (61%,; P < 0.001) were more frequent in group 2 than in the control group (20.17% ; 47%). Neither the homozygous nor the heterozygous MTHFR C677T mutation al one was found to be a risk factor for leukoaraiosis. The homozygous MTHFR C 677T mutation combined with the ACE D/D genotype was significantly more fre quent in group 1 (11.89%), P < 0.0005; OR 4.75, 95% CI, 2.12-10.65), in gro up 2 (12.79%, P <0.0005; OR 5.16, 95% CI, 2.12-12.6) and in combined group 1 + 2 (12.23%, P <0.0005: OR 4.9, 95% CI, 2.33-10.3) than in the control gr oup (2.76%). Conclusion - These data indicate that the contributions of the ACE D/D genotype and the homozygous MTHFR C677T mutation to leukoaraiosis should be taken into consideration not as major, but as additive factors. T hese findings draw attention to the fact that genetic polymorphisms that al one are insignificant can be risk factors for leukoaraiosis if they cluster in the same subjects.