Association between well-characterized lipoprotein-related genetic variants and carotid intimal medial thickness and stenosis: The Framingham Heart Study.
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.
Elosua
Roberto
R
The Department of Biostatistics, Boston University, Boston, MA, United States; The USDA Human Nutrition Research Center on Aging, Tufts University, MA, USA.
Cupples
L Adrienne
LA
Fox
Caroline S
CS
Polak
Joseph F
JF
D'Agostino
Ralph A
RA
Wolf
Philip A
PA
O'Donnell
Christopher J
CJ
Ordovas
Jose M
JM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D053305:Apolipoprotein C-III / Q000235:genetics*; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging*; D002343:Carotid Artery, Internal / Q000000981:diagnostic imaging*; D016893:Carotid Stenosis / Q000097:blood / Q000000981:diagnostic imaging / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics; D004247:DNA / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008071:Lipoprotein Lipase / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D012307:Risk Factors; D017539:Tunica Intima / Q000000981:diagnostic imaging*; D018608:Ultrasonography, Doppler
D053305:Apolipoprotein C-III; D053480:Cholesterol Ester Transfer Proteins; D004247:DNA; D008071:Lipoprotein Lipase