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

PLoS One. 2014 Feb 13;9(2):e88749. doi: 10.1371/journal.pone.0088749. eCollection 2014.

Abstract

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 = -.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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Asian People
  • Catechol O-Methyltransferase / genetics*
  • Cognition / physiology*
  • Cognition Disorders / ethnology
  • Cognition Disorders / genetics
  • Cognition Disorders / pathology
  • Corpus Callosum / anatomy & histology*
  • Corpus Callosum / enzymology
  • Female
  • Frontal Lobe / anatomy & histology*
  • Frontal Lobe / enzymology
  • Gene Expression
  • Genotype
  • Heterozygote
  • Homozygote
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Nerve Fibers, Myelinated / enzymology
  • Neuropsychological Tests
  • Polymorphism, Genetic*

Substances

  • COMT protein, human
  • Catechol O-Methyltransferase

Grants and funding

This work was supported by grants V101C-006, VGHUST101-G1-1-1, VGHUST102- G1-2-1 from Taipei Veterans General Hospital, Taiwan, grants NSC 102-2314-B-075B-001, NSC 101-2321-B-010 -026 -, NSC 101-2911-I-008-001, NSC 101-2314-B-075 -040, and NSC 101-2911-I-008-001 from National Science Council Grant, Taiwan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.