P-selectin expression tracks cerebral atrophy in Mexican-Americans

P. Kochunov, D. C. Glahn, L. E. Hong, J. Lancaster, J. E. Curran, M. P. Johnson, A. M. Winkler, H. H. Holcomb, Jr W. Kent, B. Mitchell, V. Kochunov, R. L. Olvera, S. A. Cole, T. D. Dyer, E. K. Moses, H. Goring, L. Almasy, R. Duggirala, J. Blangero

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Background and Purpose: We hypothesized that the P-selectin (SELP) gene, localized to a region on chromosome 1q24, pleiotropically contributes to increased blood pressure and cerebral atrophy. We tested this hypothesis by performing genetic correlation analyses for 13 mRNA gene expression measures from P-selectin and 11 other genes located in 1q24 region and three magnetic resonance imaging derived indices of cerebral integrity. Methods: The subject pool consisted of 369 (219F; aged 28-85, aver-age = 47.1 ± 12.7years) normally aging, community-dwelling members of large extended Mexican-American families. Genetic correlation analysis decomposed phenotypic correlation coefficients into genetic and environmental components among 13 leukocyte-based mRNA gene expressions and three whole-brain and regional measurements of cerebral integrity: cortical gray matter thickness, fractional anisotropy of cerebral white matter, and the volume of hyperintensive WM lesions. Results: From the 13 gene expressions, significant phenotypic correlations were only found for the P-and L-selectin expression levels. Increases in P-selectin expression levels tracked with decline in cerebral integrity while the opposite trend was observed for L-selectin expression. The correlations for the P-selectin expression were driven by shared genetic factors, while the correlations with L-selectin expression were due to shared environmental effects. Conclusion: This study demonstrated that P-selectin expression shared a significant variance with measurements of cerebral integrity and posits elevated P-selectin expression levels as a potential risk factor of hypertension-related cerebral atrophy.

Original languageEnglish (US)
Article numberArticle 65
JournalFrontiers in Genetics
Volume3
Issue numberMAY
DOIs
StatePublished - 2012

Keywords

  • Aging
  • Cerebral atrophy
  • DTI
  • Gene expression
  • Genetics
  • Hypertension
  • P-selectin

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Genetics(clinical)

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