Werner syndrome protein 1367 variants and disposition towards coronary artery disease in Caucasian patients

Vilhelm A. Bohr, E. Metter, Jeanine A. Harrigan, Cayetano Von Kobbe, Ji Lan Liu, Matthew D. Gray, Alokes Majumdar, David M. Wilson, Michael M. Seidman

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

The leading causes of death for individuals with Werner syndrome (WS) are myocardial infarction (MI) and stroke. The WS gene encodes a nuclear protein with both helicase and exonuclease activities. While individuals with WS have mutations that result in truncated, inactive proteins, several sequence variants have been described in apparently unaffected individuals. Some of these gene polymorphisms encode non-conservative amino acid substitutions, and it is expected that the changes would affect enzyme activity, although this has not been determined. Two research groups have studied the Cys/Arg 1367 polymorphism (located near the nuclear localization signal) in healthy and MI patients. Their results suggest that the Arg allele is protective against MI. We have characterized the Cys (C) and Arg (R) forms of the protein and find no notable difference in helicase and nuclease activities, or in nuclear/cytoplasmic distribution. The frequency of the C/R alleles in healthy individuals and subjects with coronary artery disease (CAD) drawn from the Baltimore Longitudinal Study of Aging (BLSA) was also examined. There was no indication that the R allele was protective against CAD. We conclude that the C/R polymorphism does not affect enzyme function or localization and does not influence CAD incidence in the BLSA cohort.

Original languageEnglish (US)
Pages (from-to)491-496
Number of pages6
JournalMechanisms of Ageing and Development
Volume125
Issue number7
DOIs
StatePublished - Jul 1 2004
Externally publishedYes

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Werner Syndrome
Coronary Artery Disease
Baltimore
Alleles
Myocardial Infarction
Longitudinal Studies
Nuclear Localization Signals
Exonucleases
Proteins
Enzymes
Amino Acid Substitution
Nuclear Proteins
Genes
Cause of Death
Healthy Volunteers
Stroke
Mutation
Incidence
Research

All Science Journal Classification (ASJC) codes

  • Aging
  • Developmental Biology

Cite this

Werner syndrome protein 1367 variants and disposition towards coronary artery disease in Caucasian patients. / Bohr, Vilhelm A.; Metter, E.; Harrigan, Jeanine A.; Von Kobbe, Cayetano; Liu, Ji Lan; Gray, Matthew D.; Majumdar, Alokes; Wilson, David M.; Seidman, Michael M.

In: Mechanisms of Ageing and Development, Vol. 125, No. 7, 01.07.2004, p. 491-496.

Research output: Contribution to journalArticle

Bohr, VA, Metter, E, Harrigan, JA, Von Kobbe, C, Liu, JL, Gray, MD, Majumdar, A, Wilson, DM & Seidman, MM 2004, 'Werner syndrome protein 1367 variants and disposition towards coronary artery disease in Caucasian patients', Mechanisms of Ageing and Development, vol. 125, no. 7, pp. 491-496. https://doi.org/10.1016/j.mad.2004.05.001
Bohr, Vilhelm A. ; Metter, E. ; Harrigan, Jeanine A. ; Von Kobbe, Cayetano ; Liu, Ji Lan ; Gray, Matthew D. ; Majumdar, Alokes ; Wilson, David M. ; Seidman, Michael M. / Werner syndrome protein 1367 variants and disposition towards coronary artery disease in Caucasian patients. In: Mechanisms of Ageing and Development. 2004 ; Vol. 125, No. 7. pp. 491-496.
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