title: Genetic variation on chromosome 16 is associated with abdominal aortic aneurysm.
abstract: 1. There is a familial tendency to abdominal aortic aneurysms. We have followed up a previous report of a weak association between the haptoglobin 2-1 phenotype and aortic aneurysm and investigated polymorphisms of the haptoglobin gene and neighbouring cholesterol ester transfer protein gene on the long arm of chromosome 16 in patients with atherosclerotic abdominal aortic aneurysm, patients with stenosing aortic atherosclerosis and healthy control subjects. The protein polymorphism of haptoglobin results from variant alpha-chains, alpha 1 and alpha 2, the phenotype nomenclature describing the two alpha-chains. We have also investigated whether the different haptoglobin phenotypes influence the degradation of aortic connective tissue. 2. The frequency of the haptoglobin alpha 1 allele was increased in patients with aneurysms compared with healthy control subjects (0.51 versus 0.35, P less than 0.05). Patients homozygous for the alpha 2 allele had the highest mean age at aneurysm resection. The frequency of a rare polymorphism at the cholesterol ester transfer protein locus was also increased in aneurysm patients (0.15 versus 0.05 in control subjects, P less than 0.01). These two genetic markers appear to act independently. Haptoglobins containing an alpha 1-chain accelerated two- to four-fold the degradation by elastases of aortic elastin in vitro. 3. Genetic variation in the haptoglobin and cholesterol ester transfer protein genes appears to influence dilatation of the abdominal aorta. Variation at the haptoglobin locus could have a direct effect on the degradation of elastin in atherosclerotic aorta, whereas variation at the cholesterol ester transfer protein locus could affect lipid metabolism and promote atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Surgery, Charing Cross and Westminster Medical School, London.
authors.forename: J T
authors.initials: JT
authors.lastname: Powell
authors.forename: A
authors.initials: A
authors.lastname: Bashir
authors.forename: S
authors.initials: S
authors.lastname: Dawson
authors.forename: N
authors.initials: N
authors.lastname: Vine
authors.forename: A M
authors.initials: AM
authors.lastname: Henney
authors.forename: S E
authors.initials: SE
authors.lastname: Humphries
authors.forename: R M
authors.initials: RM
authors.lastname: Greenhalgh
mesh_terms: D000368:Aged; D001012:Aorta, Abdominal; D001014:Aortic Aneurysm / Q000235:genetics*; D001053:Apolipoproteins / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D002885:Chromosomes, Human, Pair 16; D005260:Female; D014644:Genetic Variation; D006023:Glycoproteins / Q000235:genetics; D006242:Haptoglobins / Q000235:genetics; D006801:Humans; D008297:Male; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D001053:Apolipoproteins; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D006023:Glycoproteins; D006242:Haptoglobins