title: The candidate gene approach to susceptibility for abdominal aortic aneurysm: TIMP1, HLA-DR-15, ferritin light chain, and collagen XI-Alpha-1.
abstract: There are two approaches to gene discovery for diseases when genetic susceptibility has been implicated by clinical genetic or case-control studies: (1) genome-wide screening and (2) evaluation of candidate genes. Each has specific advantages and disadvantages. The principal advantage of genome-wide screening is that it is impeccably objective in as much as it proceeds without any presuppositions regarding the importance of specific pathobiological features of the disease process. The principal disadvantage is that such a study is expensive and resource intensive. A large population of enrolled patients and multidisciplinary teams of investigators cooperating from several institutions are usually required. The alternative approach of evaluating candidate genes can be pursued by a small independent laboratory with limited funding and resources, a small collection of clinical specimens, and a small number of team players. The disadvantage is that it is by necessity highly subjective in the process of selecting specific candidates among many reasonable possibilities. There is no a priori assurance that effort will not be expended on one or more candidates that turn out in the end to be failures. This report reviews efforts in our laboratory to evaluate four genes as candidates. One of these tissue inhibitor of metalloprotease 1(TIMP1) led to the description of a polymorphism, but not a conclusive mutation. The other three (HLA-DR-15, ferritin light chain (FTL), and collagen XI-alpha-1 (COL11A1) are subjects of continuing interest.
authors.affiliation: Department of Surgery, St. Luke's-Roosevelt Hospital Center, Continuum Health Partners, New York, New York 10019, USA. mdt1@columbia.edu
authors.forename: M David
authors.initials: MD
authors.lastname: Tilson
authors.forename: Charles Y
authors.initials: CY
authors.lastname: Ro
mesh_terms: D017544:Aortic Aneurysm, Abdominal / Q000235:genetics*; D003094:Collagen / Q000145:classification / Q000235:genetics*; D005293:Ferritins / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D059810:HLA-DR Serological Subtypes; D006801:Humans; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics*
chemical_list: D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C106559:HLA-DR15 antigen; D019715:Tissue Inhibitor of Metalloproteinase-1; D003094:Collagen; D005293:Ferritins