BACKGROUND: Carriers of the 719Arg variant in KIF6, compared with noncarriers, have been reported to be at greater risk for coronary heart disease (CHD) in six prospective studies. Because CHD, thoracic aortic dissection, and nondissection thoracic aortic aneurysm share some risk factors and aspects of pathophysiology, we investigated whether carriers of the 719Arg variant also have greater odds of thoracic aortic dissection or nondissected thoracic aortic aneurysm than noncarriers. METHODS: We genotyped 140 thoracic aortic dissection cases, 497 nondissection thoracic aortic aneurysm cases, and 275 disease-free controls collected in the United States, Hungary, and Greece and investigated the association between KIF6 719Arg carrier status and thoracic aortic dissection, and between KIF6 719Arg carrier status and nondissection thoracic aortic aneurysm, using logistic regression models adjusted for age, sex, hypertension, smoking, and country. RESULTS: The odds of aortic dissection were two-fold greater in KIF6 719Arg carriers compared with noncarriers (odds ratio (OR) 2.14, 95% confidence interval (CI) 1.18-3.9). To account for the potential of concomitant CHD to confound the association between the KIF6 719Arg and thoracic aortic dissection, we repeated the analysis after removing subjects with concomitant CHD; the estimates for association of KIF6 719Arg carrier status remained essentially the same (OR 2.04, 95% CI 1.11-3.77). In contrast, KIF6 719Arg carrier status was not associated with risk for nondissection thoracic aortic aneurysm. CONCLUSIONS: We observed an association of the KIF6 719Arg genetic variant with thoracic aortic dissection in this multicenter case-control study. This association may enhance our management of patients with thoracic aortic disease.
BACKGROUND: Carriers of the 719Arg variant in KIF6, compared with noncarriers, have been reported to be at greater risk for coronary heart disease (CHD) in six prospective studies. Because CHD, thoracic aortic dissection, and nondissection thoracic aortic aneurysm share some risk factors and aspects of pathophysiology, we investigated whether carriers of the 719Arg variant also have greater odds of thoracic aortic dissection or nondissected thoracic aortic aneurysm than noncarriers. METHODS: We genotyped 140 thoracic aortic dissection cases, 497 nondissection thoracic aortic aneurysm cases, and 275 disease-free controls collected in the United States, Hungary, and Greece and investigated the association between KIF6 719Arg carrier status and thoracic aortic dissection, and between KIF6 719Arg carrier status and nondissection thoracic aortic aneurysm, using logistic regression models adjusted for age, sex, hypertension, smoking, and country. RESULTS: The odds of aortic dissection were two-fold greater in KIF6 719Arg carriers compared with noncarriers (odds ratio (OR) 2.14, 95% confidence interval (CI) 1.18-3.9). To account for the potential of concomitant CHD to confound the association between the KIF6 719Arg and thoracic aortic dissection, we repeated the analysis after removing subjects with concomitant CHD; the estimates for association of KIF6 719Arg carrier status remained essentially the same (OR 2.04, 95% CI 1.11-3.77). In contrast, KIF6 719Arg carrier status was not associated with risk for nondissection thoracic aortic aneurysm. CONCLUSIONS: We observed an association of the KIF6 719Arg genetic variant with thoracic aortic dissection in this multicenter case-control study. This association may enhance our management of patients with thoracic aortic disease.
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Authors: Dov Shiffman; Daniel I Chasman; Robert Y L Zee; Olga A Iakoubova; Judy Z Louie; James J Devlin; Paul M Ridker Journal: J Am Coll Cardiol Date: 2008-01-29 Impact factor: 24.094