Association between well-characterized lipoprotein-related genetic variants and carotid intimal medial thickness and stenosis: The Framingham Heart Study

被引:14
作者
Elosua, Roberto
Cupples, L. Adrienne
Fox, Caroline S.
Polak, Joseph F.
D'Agostino, Ralph A., Sr.
Wolf, Philip A.
O'Donnell, Christopher J.
Ordovas, Jose M.
机构
[1] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA
[2] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA
[3] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA
[4] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA
[5] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA
[6] Boston Univ, Sch Med, Dept Prevent Med & Epidemiol, Boston, MA 02118 USA
[7] Boston Univ, Dept Biostat, Boston, MA 02215 USA
[8] Tufts Univ, USDA, Human Nutr Res Ctr Aging, Medford, MA 02155 USA
[9] Inst Municipal Invest Med, E-08003 Barcelona, Spain
[10] NHLBI, NIH, Bethesda, MD 20892 USA
关键词
carotid; epidemiology; genetics; lipids;
D O I
10.1016/j.atherosclerosis.2005.12.005
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: To determine the association of well-characterized lipoprotein-related genetic variants with carotid intimal medial thickness (IMT) and stenosis. Methods: 3380 men and women from the Framingham Offspring Study underwent carotid ultrasound to determine carotid IMT and stenosis >= 25%. We genotyped 12 variants in 10 lipoprotein-related genes known to be associated with significant differences in lipoprotein levels. Results: For most of the variants, there was no association with carotid IMT. In multivariable, sex-specific analyses, the rare allele of the cholesterol ester transfer protein (CETP) TaqIB variant was associated with lower ICA IMT in men. Hypertension was associated with higher ICA IMT only in male carriers of the rare allele of the APOCIII Sst-1 variant (p for the interaction=0.041). In analyses of carotid stenosis in male, carriers of the lipoprotein lipase (LPL) N291S rare variant showed a higher risk of carotid stenosis (OR = 2.59, 95% confidence interval: 1.11-6.02, p=0.028) compared to NN genotype. Conclusions: While there is no evidence for a significant association of several common lipoprotein-related genetic variants with carotid IMT, our results are consistent with the previously reported role of CETP and LPL genetic variants in cardiovascular risk and the possible modulation of the association between hypertension and carotid IMT by APOCIII Sst-1 variant. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:222 / 228
页数:7
相关论文
共 27 条
[1]   Differences between carotid wall morphological phenotypes measured by ultrasound in one, two and three dimensions [J].
Al-Shali, K ;
House, AA ;
Hanley, AJG ;
Khan, HMR ;
Harris, SB ;
Mamakeesick, M ;
Zinman, B ;
Fenster, A ;
Spence, JD ;
Hegele, RA .
ATHEROSCLEROSIS, 2005, 178 (02) :319-325
[2]   Cholesteryl ester transfer protein TaqIB variant, high-density lipoprotein cholesterol levels, cardiovascular risk, and efficacy of pravastatin treatment - Individual patient meta-analysis of 13,677 subjects [J].
Boekholdt, SM ;
Sacks, FM ;
Jukema, JW ;
Shepherd, J ;
Freeman, DJ ;
McMahon, AD ;
Cambien, F ;
Nicaud, V ;
de Grooth, GJ ;
Talmud, PJ ;
Humphries, SE ;
Miller, GJ ;
Eiriksdottir, G ;
Gudnason, V ;
Kauma, H ;
Kakko, S ;
Savolainen, MJ ;
Arca, M ;
Montali, A ;
Liu, S ;
Lanz, HJ ;
Zwinderman, AH ;
Kuivenhoven, JA ;
Kastelein, JJP .
CIRCULATION, 2005, 111 (03) :278-287
[3]   Cholesteryl ester transfer protein TaqI B2B2 genotype is associated with higher HDL cholesterol levels and lower risk of coronary heart disease end points in men with HDL deficiency -: Veterans Affairs HDL Cholesterol Intervention Trial [J].
Brousseau, ME ;
O'Connor, JJ ;
Ordovas, JM ;
Collins, D ;
Otvos, JD ;
Massov, T ;
McNamara, JR ;
Rubins, HB ;
Robins, SJ ;
Schaefer, EJ .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2002, 22 (07) :1148-1154
[4]   Absence of association between genetic variation in the promoter of the microsomal triglyceride transfer protein gene and plasma lipoproteins in the Framingham Offspring Study [J].
Couture, P ;
Otvos, JD ;
Cupples, LA ;
Wilson, PWF ;
Schaefer, EJ ;
Ordovas, JM .
ATHEROSCLEROSIS, 2000, 148 (02) :337-343
[5]  
Couture P, 1999, J LIPID RES, V40, P1883
[6]   Genomewide linkage analysis for internal carotid artery intimal medial thickness: Evidence for linkage to chromosome 12 [J].
Fox, CS ;
Cupples, LA ;
Chazaro, I ;
Polak, JF ;
Wolf, PA ;
D'Agostino, RB ;
Ordovas, JM ;
O'Donnell, CJ .
AMERICAN JOURNAL OF HUMAN GENETICS, 2004, 74 (02) :253-261
[7]   Genetic and environmental contributions to atherosclerosis phenotypes in men and women - Heritability of carotid intima-media thickness in the Framingham Heart Study [J].
Fox, CS ;
Polak, JF ;
Chazaro, I ;
Cupples, A ;
Wolf, PA ;
D'Agostino, RA ;
O'Donnell, CJ .
STROKE, 2003, 34 (02) :397-401
[8]   A common truncation variant of lipoprotein lipase (Ser447X) confers protection against coronary heart disease:: the Framingham Offspring Study [J].
Gagné, SE ;
Larson, MG ;
Pimstone, SN ;
Schaefer, EJ ;
Kastelein, JJP ;
Wilson, PWF ;
Ordovas, JM ;
Hayden, MR .
CLINICAL GENETICS, 1999, 55 (06) :450-454
[9]   Association of the A/T54 polymorphism in the intestinal fatty acid binding protein with variations in plasma lipids in The Framingham Offspring Study [J].
Galluzzi, JR ;
Cupples, LA ;
Otvos, JD ;
Wilson, PWF ;
Schaefer, EJ ;
Ordovas, JM .
ATHEROSCLEROSIS, 2001, 159 (02) :417-424
[10]   Lipoprotein lipase gene polymorphisms in ischaemic stroke and carotid stenosis [J].
Huang, P ;
Kostulas, K ;
Huang, WX ;
Crisby, M ;
Kostulas, V ;
Hillert, J .
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, 1997, 27 (09) :740-742