Proteolytic imbalance may play a role in the pathogenesis of abdominal aortic aneurysms (AAA). CLG4B, which encodes the 92-kDa form of type IV collagenase, is a candidate gene for AAA. We genotyped a polymorphic dinucleotide repeat in the 5' flanking region of CLG4B in 94 unrelated Caucasian controls and in 127 unrelated Caucasian AAA cases. Eight alleles were detected in 188 control chromosomes with an observed heterozygosity of 0.68. There was no significant difference in allele distribution between cases and controls. We genotyped the dinucleotide repeat in 10 CEPH reference pedigrees and performed pairwise linkage analysis with markers on each of the 22 human autosomes. Lod scores between 10.45 and 20.29 were observed with markers spanning chromosome region 20q11.2-q13.1. Further support for assignment of CLG4B to chromosome 20 was provided by analysis of human-rodent somatic cell hybrids. This work describes a highly polymorphic marker in the CLG4B gene and assigns this gene to chromosome 20.
α1-Antitrypsin (α1-AT) deficiency may play a role in arterial aneurysmal disease by allowing increased proteolysis of arterial structural proteins. α1-AT levels are influenced by variation at the PI (protease inhibitor) locus. PI phenotypes were determined in 173 patients with abdominal aortic aneurysms (77 from Pitsburgh, 96 from London) and in 72 patients with intracranial aneurysms (26 from Pittsburgh, 46 from London). No excess of PI deficiency alleles was observed in either of the aortic aneurysm data sets or in the Pittsburgh intracranial aneurysm data. The PPZ deficiency allele frequency in the London intracranial aneurysm data was 8-fold higher than in controls; however, this was not significant after correcting for multiple comparisons. PI phenotype had no effect on aneurysm age-at-diagnosis within any of the data sets. Smoking history had an effect on aneurysm age-at-diagnosis only within the Pittsburgh intracranial-aneurysm data.
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