title: Segment-specific genetic effects on carotid intima-media thickness: the Northern Manhattan study.
abstract: 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.
authors.affiliation: Graduate Institute of Medical Genetics, the Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Yi-Chu
authors.initials: YC
authors.lastname: Liao
authors.forename: Hsiu-Fen
authors.initials: HF
authors.lastname: Lin
authors.forename: Tatjana
authors.initials: T
authors.lastname: Rundek
authors.forename: Rong
authors.initials: R
authors.lastname: Cheng
authors.forename: Yuh-Cherng
authors.initials: YC
authors.lastname: Guo
authors.forename: Ralph L
authors.initials: RL
authors.lastname: Sacco
authors.forename: Suh-Hang Hank
authors.initials: SH
authors.lastname: Juo
mesh_terms: 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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