Journal
CIRCULATION
Volume 113, Issue 18, Pages 2193-2200Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCULATIONAHA.106.615401
Keywords
genetics; multilocus; polymorphisms; risk factors; venous thromboembolism
Funding
- NHLBI NIH HHS [HL-58755, HL-63293] Funding Source: Medline
Ask authors/readers for more resources
Background - Candidate genes in inflammation, thrombosis, coagulation, and lipid metabolism pathways have been implicated in venous thromboembolism (VTE). Methods and Results - Using DNA samples collected at baseline in the Physicians' Health Study cohort, we genotyped 92 polymorphisms from 56 candidate genes among 304 individuals who subsequently developed VTE (144 idiopathic, 156 secondary cases) and among 2070 individuals who remained free of reported vascular disease over a mean follow-up of 13.2 years to prospectively determine whether these gene polymorphisms contribute to the risk of VTE. For idiopathic VTE, in addition to the factor V (Leiden) mutation (odds ratio [OR], 5.13; 95% confidence interval [CI], 3.24 to 8.14; P < 0.0001; false discovery rate [FDR], P < 0.0001), an N291S lipoprotein lipase gene polymorphism (OR, 3.09; 95% CI, 1.56 to 6.09; P = 0.001; FDR, P = 0.036) and a Q27E beta(2)-adrenergic receptor gene polymorphism (OR, 1.40; 95% CI, 1.09 to 1.79; P = 0.006; FDR, P = 0.036) were found to be significantly associated with increased risk. For secondary VTE, a Q360H apolipoprotein A4 gene polymorphism (OR, 0.34; 95% CI, 0.18 to 0.65; P = 0.001; FDR, P = 0.07) and an I50V interleukin-4 receptor polymorphism (OR, 0.66; 95% CI, 0.52 to 0.84; P = 0.0009; FDR, P = 0.07) were moderately, but not statistically and significantly, associated with reduced risk after adjustment for multiple comparisons. Conclusions - These present findings are hypothesis generating and require replication and confirmation in an independent investigation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available