Catechol-O-Methyltransferase Val158Met Polymorphism on the Relationship between White Matter Hyperintensity and Cognition in Healthy People

<div><p>Background</p><p>White matter lesions can be easily observed on T2-weighted MR images, and are termed white matter hyperintensities (WMH). Their presence may be correlated with cognitive impairment; however, the relationship between regional WMH volume and catechol-O-methyltransferase (COMT) Val158Met polymorphism in healthy populations remains unclear.</p><p>Methods</p><p>We recruited 315 ethnic Chinese adults with a mean age of 54.9±21.8 years (range: 21–89 y) to examine the genetic effect of COMT on regional WMH and the manner in which they interact to affect cognitive function in a healthy adult population. Cognitive tests, structural MRI scans, and genotyping of COMT were conducted for each participant.</p><p>Results</p><p>Negative correlations between the Digit Span Forward (DSF) score and frontal WMH volumes (r = −.123, <i>P = </i>.032, uncorrected) were noted. For the genetic effect of COMT, no significant difference in cognitive performance was observed among 3 genotypic groups. However, differences in WMH volumes over the subcortical region (<i>P = </i>.016, uncorrected), whole brain (<i>P = </i>.047, uncorrected), and a trend over the frontal region (<i>P = </i>.050, uncorrected) were observed among 3 COMT genotypic groups. Met homozygotes and Met/Val heterozygotes exhibited larger WMH volumes in these brain regions than the Val homozygotes. Furthermore, a correlation between the DSF and regional WMH volume was observed only in Met homozygotes. The effect size (cohen’s f) revealed a small effect.</p><p>Conclusions</p><p>The results indicate that COMT might modulate WMH volumes and the effects of WMH on cognition.</p>