Association of genetic variation on chromosome 9p21 with susceptibility and progression of atherosclerosis: a population-based, prospective study.
OBJECTIVE
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.
Ye
Shu
S
Clinical Pharmacology, William Harvey Research Institute, Barts and the London School of Medicine, London, United Kingdom. s.ye@qmul.ac.uk
Willeit
Johann
J
Kronenberg
Florian
F
Xu
Qingbo
Q
Kiechl
Stefan
S
D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging / Q000235:genetics*; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012044:Regression Analysis; D018616:Ultrasonography, Doppler, Duplex