Association of Genetic Variation on Chromosome 9p21 With Susceptibility and Progression of Atherosclerosis. A Population-Based, Prospective Study

Abstract

Objectives: Following the recent novel finding from genomewide association studies that sequence variation on chromosome 9p21 is a genetic factor for coronary artery disease, we investigated whether the genetic variant influenced the development of atherosclerosis and its progression in a population-based, prospective study. Background: Recently, several genomewide association studies revealed a highly significant association between variation on chromosome 9p21 and risk of coronary artery disease. Methods: We studied the rs1333049 polymorphism located on chromosome 9p21 in a cohort of 769 individuals who participated in the Bruneck study with long-term follow-up data on carotid atherosclerosis measured by high-resolution duplex ultrasound and incident cardiovascular disease. Results: The C allele was associated not only with prevalent carotid atherosclerosis (odds ratio [OR]: 1.46 [95% confidence interval (CI): 1.13 to 1.88]; OR: 1.43 [95% CI: 1.11 to 1.84]; and OR: 1.44 [95% CI: 1.11 to 1.87] for each copy of C allele, calculated from data collected in 1990, 1995, and 2000, respectively), but also with progression of atherosclerosis (OR: 1.73 [95% CI: 1.36 to 2.21] during 1990 to 1995, and OR: 1.87 [95% CI: 1.44 to 2.42] during 1995 to 2000). In addition, the C allele was related to incident cardiovascular disease (hazard ratio: 1.37 [95% CI: 1.05 to 1.79]). There was evidence of an interaction between genotype and abdominal obesity on atherosclerosis and cardiovascular risk. Conclusions: The results of this population-based, prospective study indicate that the sequence variation on chromosome 9p21 influences atherosclerosis development and progression. © 2008 American College of Cardiology Foundation.