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.
