title: Analysis of sequence variations in the ABCC6 gene among patients with abdominal aortic aneurysm and pseudoxanthoma elasticum.
abstract: Abdominal aortic aneurysm (AAA) is characterized by dilatation of arterial walls, which is accompanied by degradation of elastin and collagen molecules. Biochemical and environmental factors are known to be relevant for AAA development, and familial predisposition is well recognized. A connective tissue disorder that is also associated with fragmentation of elastic fibers is Pseudoxanthoma elasticum (PXE). PXE is caused by mutations in the ABCC6 gene and mainly affects dermal, ocular and all vascular tissues. To investigate whether variations in ABCC6 are found in AAA patients and to determine mutations in PXE patients, we analyzed seven selected ABCC6 exons of 133 AAA and 54 PXE patients subjected to mutational analysis. In our cohort of AAA patients, we found five ABCC6 alterations, which result in missense or silent amino acid variants. The allelic frequencies of these sequence variations were not significantly different between AAA patients and healthy controls. Therefore, we suggest that alterations in ABCC6 are not a genetic risk factor for AAA. Mutational screening of the PXE patients revealed 19 different ABCC6 variations, including two novel PXE-causing mutations. These results expand the ABCC6 mutation database in PXE.
authors.affiliation: Institut fur Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitatsklinik der Ruhr-Universitat Bochum, Bad Oeynhausen, Freudenberg, Deutschland.
authors.forename: Veronika
authors.initials: V
authors.lastname: Schulz
authors.forename: Doris
authors.initials: D
authors.lastname: Hendig
authors.forename: Martin
authors.initials: M
authors.lastname: Schillinger
authors.forename: Markus
authors.initials: M
authors.lastname: Exner
authors.forename: Hans
authors.initials: H
authors.lastname: Domanovits
authors.forename: Marianne
authors.initials: M
authors.lastname: Raith
authors.forename: Christiane
authors.initials: C
authors.lastname: Szliska
authors.forename: Knut
authors.initials: K
authors.lastname: Kleesiek
authors.forename: Christian
authors.initials: C
authors.lastname: Gotting
mesh_terms: D000328:Adult; D000368:Aged; D017544:Aortic Aneurysm, Abdominal / Q000453:epidemiology / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000737:chemistry / Q000235:genetics*; D011110:Polymorphism, Genetic; D017434:Protein Structure, Tertiary; D011561:Pseudoxanthoma Elasticum / Q000453:epidemiology / Q000235:genetics*; D012307:Risk Factors
chemical_list: D027425:ATP-Binding Cassette, Sub-Family C Proteins; C102029:ABCC6 protein, human