title: Frequent mutation in the ABCC6 gene (R1141X) is associated with a strong increase in the prevalence of coronary artery disease.
abstract: BACKGROUND
  Pseudoxanthoma elasticum (PXE) is an inborn disorder of the connective tissue with specific skin, ocular, and cardiovascular disease (CVD) manifestations. Recently, we and others have identified mutations in the gene coding for the ABCC6 transporter in PXE patients with ocular and skin involvement. In the Netherlands, as in the rest of Europe, a particular premature truncation variant ABCC6 (R1141X) was found in a large cohort of PXE patients. Given the association between CVD and PXE, we hypothesized that heterozygosity of this ABCC6 mutation could also confer an increased risk for CVD.
  
  
  RESULTS
  To assess the relationship between the frequent R1141X mutation in the ABCC6 gene and the prevalence of premature coronary artery disease (CAD), we conducted a case-control study of 441 patients under the age of 50 years who had definite CAD and 1057 age- and sex-matched population-based controls who were free of coronary disease. Strikingly, the prevalence of the R1141X mutation was 4.2 times higher among patients than among controls (3.2% versus 0.8%; P<0.001). Consequently, among subjects with the R1141X mutation, the odds ratio for a coronary event was 4.23 (95% CI: 1.76 to 10.20, P= 0.001).
  
  
  CONCLUSIONS
  The presence of the R1141X mutation in the ABCC6 gene is associated with a sharply increased risk of premature CAD.
authors.affiliation: Department of Cardiology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. M.D.Trip@AMC.UVA.NL
authors.forename: Mieke D
authors.initials: MD
authors.lastname: Trip
authors.forename: Yvo M
authors.initials: YM
authors.lastname: Smulders
authors.forename: Jurgen J
authors.initials: JJ
authors.lastname: Wegman
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Hu
authors.forename: Jolanda M A
authors.initials: JM
authors.lastname: Boer
authors.forename: Jacoline B
authors.initials: JB
authors.lastname: ten Brink
authors.forename: Aeilko H
authors.initials: AH
authors.lastname: Zwinderman
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: Edith J M
authors.initials: EJ
authors.lastname: Feskens
authors.forename: Arthur A B
authors.initials: AA
authors.lastname: Bergen
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D009154:Mutation; D009426:Netherlands / Q000453:epidemiology; D016017:Odds Ratio; D015995:Prevalence; D011561:Pseudoxanthoma Elasticum / Q000235:genetics; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D027425:ATP-Binding Cassette, Sub-Family C Proteins; C102029:ABCC6 protein, human