Published online before print February 3, 2005, doi: 10.1161/01.STR.0000155746.65185.4e
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Stroke. 2005;36:540.)
© 2005 American Heart Association, Inc.
Original Contributions |
A Genome-Wide Scan for Carotid Artery Intima-Media Thickness
The Mexican-American Coronary Artery Disease Family Study
From the Medical Genetics Institute (D.W., H.Y., K.D.T., J.I.R.), Steven Spielberg Pediatric Research Center, Cedars-Sinai Medical Center, Los Angeles, Calif; the Division of Endocrinology, Diabetes, and Hypertension (M.J.Q., I.E., X.J., R.D-L-R., W.A.H.), the Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, Calif; the Department of Medicine (T.M., K.Y.), Olive View-UCLA Medical Center, Sylmar, Calif; and the Atherosclerosis Research Unit (Y.L., H.N.H.), Division of Cardiovascular Medicine, University of Southern California, Los Angeles, Calif.
Correspondence to Dr Dai Wang, Medical Genetics Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd, SSB 378, Los Angeles, CA 90048. E-mail dai.wang{at}cshs.org
Background and Purpose— Carotid artery intima-media thickness (CIMT), a subclinical measure of atherosclerosis, is associated with coronary artery disease (CAD), and stroke. CIMT is also an important predictor of clinical cardiovascular events. To systematically identify the genetic determinants of CIMT, we performed a genome-wide scan using data from 91 2-generation Mexican American families ascertained via a parent with CAD diagnosed.
Methods— CIMT was measured in 274 adult offspring (mean age, 34.6 years) using high-resolution B-mode ultrasound; 413 subjects, including adult offspring and their parents, were genotyped using Marshfield screen set 12 (380 microsatellite markers at 
10-cM interval). Heritability was estimated using the variance component approach implemented in SOLAR. Linkage analyses were performed using both the sib-pair regression approach and the variance component approach.
Results— The estimated heritability was 0.68, 0.45, and 0.40 for unadjusted, gender- and age-adjusted, and multivariate-adjusted CIMT, respectively. The strongest evidence of linkage was found on chromosome 2 at D2S2944 (logarithm of the odds [LOD]=3.08). Other suggestive linkages were also found on chromosome 6 at D6S1022 to D6S2410 (LOD=2.21) and chromosome 13 at D13S796 to D13S895 (LOD=1.34).
Conclusions— These results show that there is a strong genetic effect on CIMT in these Mexican American CAD families. The linkage peak on chromosome 2 suggests that there is a gene (or genes) at this chromosome location influencing CIMT.
Key Words: coronary artery disease • genetics • intima-media thickness • linkage mapping • stroke
This article has been cited by other articles:
 |
|
 |
|
  X Li, K L Monda, H H H Goring, K Haack, S A Cole, V P Diego, L Almasy, S Laston, B V Howard, N M Shara, et al. Genome-wide linkage scan for plasma high density lipoprotein cholesterol, apolipoprotein A-1 and triglyceride variation among American Indian populations: the Strong Heart Family Study J. Med. Genet., July 1, 2009; 46(7): 472 - 479. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. Sacco, S. H. Blanton, S. Slifer, A. Beecham, K. Glover, H. Gardener, L. Wang, E. Sabala, S.-H. H. Juo, and T. Rundek Heritability and Linkage Analysis for Carotid Intima-Media Thickness: The Family Study of Stroke Risk and Carotid Atherosclerosis Stroke, July 1, 2009; 40(7): 2307 - 2312. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H Stein Carotid ultrasound in children: a window to arterial ageing Heart, April 1, 2009; 95(8): 611 - 612. [Full Text] [PDF]
|
|
|
|
|
|
S Barra, G Gaeta, S Cuomo, P Guarini, M C Foglia, G Capozzi, C Materazzi, and M Trevisan Early increase of carotid intima-media thickness in children with parental history of premature myocardial infarction Heart, April 1, 2009; 95(8): 642 - 645. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. S. Sutton, D. R. Crosslin, S. H. Shah, S. C. Nelson, A. Bassil, A. B. Hale, C. Haynes, P. J. Goldschmidt-Clermont, J. M. Vance, D. Seo, et al. Comprehensive genetic analysis of the platelet activating factor acetylhydrolase (PLA2G7) gene and cardiovascular disease in case-control and family datasets Hum. Mol. Genet., May 1, 2008; 17(9): 1318 - 1328. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Oda, N. Tanaka, T. Arai, J. Araki, Y. Song, L. Zhang, A. Kuchiba, T. Hosoi, T. Shirasawa, M. Muramatsu, et al. Polymorphisms in pro- and anti-inflammatory cytokine genes and susceptibility to atherosclerosis: a pathological study of 1503 consecutive autopsy cases Hum. Mol. Genet., March 15, 2007; 16(6): 592 - 599. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Xing, B. E.K. Klein, R. Klein, G. Jun, K. E. Lee, and S. K. Iyengar Genome-Wide Linkage Study of Retinal Vessel Diameters in the Beaver Dam Eye Study Hypertension, April 1, 2006; 47(4): 797 - 802. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. M. van Asselt, H. S. Kok, Y. T. van der Schouw, P. H.M. Peeters, P. L. Pearson, and D. E. Grobbee Role of Genetic Analyses in Cardiology: Part II: Heritability Estimation for Gene Searching in Multifactorial Diseases Circulation, February 28, 2006; 113(8): 1136 - 1139. [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. Pollex and R. A. Hegele Complex Trait Locus Linkage Mapping in Atherosclerosis: Time to Take a Step Back Before Moving Forward? Arterioscler Thromb Vasc Biol, August 1, 2005; 25(8): 1541 - 1544. [Full Text] [PDF]
|
|