P-selectin expression tracks cerebral atrophy in Mexican-Americans

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

Research output: Contribution to journalArticlepeer-review

10 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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