BAK1 gene variation and abdominal aortic aneurysms

Authors

  • Bruce Gottlieb,

    Corresponding author
    1. Lady Davis Institute for Medical Research, Sir Mortimer B. Davis–Jewish General Hospital, Montréal, Québec, Canada
    2. Department of Human Genetics, Department of Medicine, McGill University, Montréal, Canada
    • Lady Davis Institute for Medical Research, Sir Mortimer B. Davis–Jewish General Hospital, 3755 Côte Ste. Catherine Road, Montréal, Québec, Canada, H3T 2E1
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  • Lorraine E. Chalifour,

    1. Lady Davis Institute for Medical Research, Sir Mortimer B. Davis–Jewish General Hospital, Montréal, Québec, Canada
    2. Division of Experimental Medicine, McGill University, Montréal, Canada
    3. Departments of Endocrinology, McGill University, Montréal, Canada
    4. Bank of Montreal Research Center for the Study of Heart Disease in Woman, McGill University, Montréal, Canada
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  • Benjamin Mitmaker,

    1. Department of Surgery, Sir Mortimer B. Davis–Jewish General Hospital, McGill University, Montréal, Canada
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  • Nathan Sheiner,

    1. Department of Surgery, Sir Mortimer B. Davis–Jewish General Hospital, McGill University, Montréal, Canada
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  • Daniel Obrand,

    1. Department of Surgery, Sir Mortimer B. Davis–Jewish General Hospital, McGill University, Montréal, Canada
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  • Cherrie Abraham,

    1. Department of Surgery, Sir Mortimer B. Davis–Jewish General Hospital, McGill University, Montréal, Canada
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  • Melissa Meilleur,

    1. Lady Davis Institute for Medical Research, Sir Mortimer B. Davis–Jewish General Hospital, Montréal, Québec, Canada
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  • Tomoko Sugahara,

    1. Lady Davis Institute for Medical Research, Sir Mortimer B. Davis–Jewish General Hospital, Montréal, Québec, Canada
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  • Ghassan Bkaily,

    1. Department of Anatomy and Cell Biology, University of Sherbrooke, Quebec, Canada
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  • Morris Schweitzer

    1. Lady Davis Institute for Medical Research, Sir Mortimer B. Davis–Jewish General Hospital, Montréal, Québec, Canada
    2. Departments of Endocrinology, McGill University, Montréal, Canada
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  • Communicated by Pui-Yan Kwok

Abstract

We sought to examine the role of genetics in the multifactorial disease, abdominal aortic aneurysm (AAA), by studying sequence variation in the BAK1 gene (BAK1) that codes for an apoptotic-promoting protein, as chronic apoptosis activation has been linked to AAA development and progression. BAK1 abdominal aorta cDNA from AAA patients and nondiseased individuals were compared with each other, as well as to the BAK1 genomic sequence obtained from matching blood samples. We found specific BAK1 single nucleotide polymorphism (SNP) containing alleles in both aneurysmic (31 cases) and healthy aortic tissue (5 cases) without seeing them in the matching blood samples. These same BAK1 SNPs have been reported, although rarely (average frequency <0.06%), in reference BAK1 DNA sequences. Based on this and other similar observations, we propose a novel hypothesis postulating that multiple variants of genes may preexist in “minority” forms within specific nondiseased tissues and be selected for, when intra- and/or extracellular conditions change. Therefore, the fact that different BAK1 variants can exist in both diseased and nondiseased AA tissues compared to matching blood samples, together with the rare occurrence of these same SNPs in reference sequences, suggests that selection may be a significant factor in AAA ontogeny. Hum Mutat 30:1–5, 2009. © 2009 Wiley-Liss, Inc.

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