title: Heterozygosity for R1141X in ABCC6 and risk of ischemic vascular disease.
abstract: BACKGROUND
  Pseudoxanthoma elasticum (PXE) is an autosomal recessive disease caused by loss-of-function mutations in ABCC6 and characterized by elastic calcification leading to dermal, ocular, and ischemic vascular disease. We tested the hypothesis that heterozygosity for R1141X, the most frequent PXE-causing mutation in Caucasians, associated with risk of ischemic vascular disease, as previous studies suggested 4- to 11-fold risk of ischemic heart disease (IHD) in heterozygotes.
  
  
  RESULTS
  We studied 10,276 persons from the general population, including 1985 with IHD and 989 with ischemic cerebrovascular disease (ICVD). We examined 45,603 individuals from a cross-sectional general population study, of whom 3738 had IHD and 2335 had ICVD. Finally, we compared 4851 patients with IHD and 625 patients with ICVD with, respectively, 4851 and 625 matched control subjects. We genotyped participants in all studies for ABCC6 R1141X. The frequency of R1141X was 0.6% in all populations studied. ABCC6 R1141X genotype was not associated with an increased risk of IHD, myocardial infarction, ICVD, or ischemic stroke. Furthermore, R1141X genotype did not interact with age on risk of the largest end point, IHD. Finally, R1141X genotype did not associate with variation in plasma levels of high-sensitivity C-reactive protein, fibrinogen, blood pressure, or lipid and lipoproteins in the general population.
  
  
  CONCLUSIONS
  In 4 studies including 66 831 participants and 13 642 cases with ischemic vascular events, heterozygosity for ABCC6 R1141X did not associate with risk of IHD, myocardial infarction, ICVD, or ischemic stroke.
authors.affiliation: Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Louise S
authors.initials: LS
authors.lastname: Hornstrup
authors.forename: Anne
authors.initials: A
authors.lastname: Tybjærg-Hansen
authors.forename: Christiane L
authors.initials: CL
authors.lastname: Haase
authors.forename: Børge G
authors.initials: BG
authors.lastname: Nordestgaard
authors.forename: Henrik
authors.initials: H
authors.lastname: Sillesen
authors.forename: Peer
authors.initials: P
authors.lastname: Grande
authors.forename: Ruth
authors.initials: R
authors.lastname: Frikke-Schmidt
mesh_terms: D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000502:physiology; D002097:C-Reactive Protein / Q000032:analysis; D002561:Cerebrovascular Disorders / Q000235:genetics; D003430:Cross-Sectional Studies; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007511:Ischemia / Q000235:genetics*; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics* / Q000378:metabolism; D009203:Myocardial Infarction / Q000235:genetics; D011561:Pseudoxanthoma Elasticum / Q000235:genetics*; D012307:Risk Factors; D014652:Vascular Diseases / Q000235:genetics
chemical_list: D002097:C-Reactive Protein; D005340:Fibrinogen; D008055:Lipids; D008074:Lipoproteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C102029:ABCC6 protein, human