Segment-specific genetic effects on carotid intima-media thickness: the Northern Manhattan study.
OBJECTIVE
Carotid intima-media thickness (IMT) is a surrogate marker of subclinical atherosclerosis and a strong predictor of stroke and myocardial infarction. The object of this study was to determine the association between carotid IMT and 702 single nucleotide polymorphisms in 145 genes.


METHODS
B-mode carotid ultrasound was performed among 408 Hispanics from the Northern Manhattan Study. The common carotid artery IMT and bifurcation IMT were phenotypes of interest. Genetic effects were evaluated by the multivariate regression model adjusting for traditional vascular risk factors. For each individual, we calculated a gene risk score (GRS) defined as the total number of the significant single nucleotide polymorphisms in different genes. Subjects were then divided into 3 GRS categories using the 2 cutoff points: mean GRS +/-1 SD.


RESULTS
We identified 6 significant single nucleotide polymorphisms in 6 genes for common carotid artery IMT and 7 single nucleotide polymorphisms in 7 genes for bifurcation IMT using the probability value of 0.005 as the significant level. There were no common significant genes for both phenotypes. The most significant genes were the tissue plasminogen activator (P=0.0005 for common carotid artery IMT) and matrix metallopeptidase-12 genes (P=0.0004 for bifurcation IMT). Haplotype analysis did not yield a more significant result. Subjects with GRS >or=9 had significantly increased IMT than those with GRS <or=5 (P<0.001). GRS was an independent predictor of both common carotid artery IMT (P=2.3x10(-9)) and bifurcation MT (P=7.2x10(-8)).


CONCLUSIONS
Multiple genes contributed to the variation in carotid IMT. IMT in different carotid segments may be regulated by different sets of susceptibility genes.
Liao
Yi-Chu
YC
Graduate Institute of Medical Genetics, the Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Lin
Hsiu-Fen
HF
Rundek
Tatjana
T
Cheng
Rong
R
Guo
Yuh-Cherng
YC
Sacco
Ralph L
RL
Juo
Suh-Hang Hank
SH
D001741:Black or African American / Q000706:statistics & numerical data; D000368:Aged; D000369:Aged, 80 and over; D002340:Carotid Artery Diseases / Q000097:blood / Q000150:complications / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging / Q000648:ultrastructure*; D002343:Carotid Artery, Internal / Q000000981:diagnostic imaging / Q000648:ultrastructure*; D005260:Female; D005796:Genes; D020022:Genetic Predisposition to Disease; D006630:Hispanic or Latino / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D008875:Middle Aged; D020412:Multifactorial Inheritance; D009519:New York City / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics; D017539:Tunica Intima / Q000000981:diagnostic imaging / Q000648:ultrastructure*; D017540:Tunica Media / Q000000981:diagnostic imaging / Q000648:ultrastructure*; D014463:Ultrasonography; D044465:White People / Q000706:statistics & numerical data
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