Abstract 19298: Heterozygosity for ABCC6 R1141X Does Not Associate with Risk of Ischemic Vascular Disease in 67,000 Individuals Including 14,000 Ischemic Events
Objectives: Pseudoxathoma 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. Two recent studies including a limited number of heterozygotes, have suggested an increased risk of ischemic heart disease associated with heterozygosity for R1141X, the most frequent PXE-causing mutation in Caucasians. We tested this hypothesis.
Methods: We genotyped 10,276 individuals in the prospective Copenhagen City Heart Study(CCHS), 42,298 individuals in the cross-sectional Copenhagen General Population Study(CGPS), and, respectively, 12,495 and 1,881 individuals in two case-control studies, the Copenhagen Ischemic Heart Disease Study(CIHDS) and the Copenhagen Carotid Stroke Study(CCSS) for the ABCC6 R1141X mutation. Risk of ischemic heart disease, myocardial infarction, ischemic cerebrovascular disease, and ischemic stroke was determined in the CCHS and CGPS, and validated in the two case-control studies.
Results: The frequency of R1141X was 0.6% in all populations studied. Hazard/odds ratios for ischemic heart disease, myocardial infarction, ischemic cerebrovascular disease, or ischemic stroke overlapped 1.0 for all studies (Figure). Likewise, in the combined studies including a total of 66,950 individuals and 13,761 ischemic events, odds ratios for any ischemic event as a function of R1141X genotype was not different from 1.0. Finally, R1141X also did not associate with an increased risk of premature ischemic vascular disease in individuals <55 years of age.
Conclusion: In prospective, cross-sectional, and case-control studies including a total of 66,950 participants and 13,761 ischemic events, heterozygosity for ABCC6 R1141X did not associate with risk of ischemic heart disease, myocardial infarction, ischemic cerebrovascular disease, or ischemic stroke regardless of study design.
- © 2010 by American Heart Association, Inc.