Catechol-O-methyltransferase Val158Met polymorphism on the relationship between white matter hyperintensity and cognition in healthy people

Mu En Liu, Chu Chung Huang, Albert C. Yang, Pei Chi Tu, Heng Liang Yeh, Chen Jee Hong, Ying Jay Liou, Jin Fan Chen, Kun Hsien Chou, Ching Po Lin, Shih Jen Tsai

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Background: 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. Methods: 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. Results: Negative correlations between the Digit Span Forward (DSF) score and frontal WMH volumes (r = 2.123, P= .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 ( P= .016, uncorrected), whole brain (P= .047, uncorrected), and a trend over the frontal region (P= .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. Conclusions: The results indicate that COMT might modulate WMH volumes and the effects of WMH on cognition.

Original languageEnglish
Article numbere88749
JournalPLoS ONE
Issue number2
StatePublished - 13 Feb 2014


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