A homozygous genetic variant of mitochondrial uncoupling protein 4 affects the occurrence of leukoaraiosis

We hypothesized that an appropriate balance of the mitochondrial energy production is essential in the maintenance of the glia cells in the brain. The aim of this study was to examine the roles of the rs10807344 and rs2270450 genetic variants of mitochondrial uncoupling protein 4 in the development of vascular demyelinization of the white matter of the brain, referred to as leukoaraiosis (LA). The mUCPs are presumed to be of great importance in the regulation of the mitochondrial membrane potential (MMP) and the cellular energy metabolism.

An analysis was performed on the clinical and genetic data on 401 LA patients without infarction and on 451 neuroimaging alteration-free subjects. After univariate statistical approaches, logistic regression models were also used to adjust differences in significant clinical factors between the patients and controls.

The rs10807344 CC genotype proved to exert a protective effect on the occurrence of LA (neuroimaging alteration-free controls: 57.7%, LA group: 44.9%, P < 0.0002; adjusted OR: 0.41, 95% CI: 0.2-0.68, P < 0.005).

The present findings indirectly raise the possibility that a shift or imbalance in the finely regulated MMP may play a role in the development of LA.