Published Online
on February 3, 2005

A more recent version of this article appeared on March 1, 2005

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Submitted on September 13, 2004
Revised on November 9, 2004
Accepted on November 22, 2004

A Genome-Wide Scan for Carotid Artery Intima-Media Thickness. The Mexican-American Coronary Artery Disease Family Study

Dai Wang PhD^*; Huiying Yang MD, PhD; Manuel J. Quiñones MD; Isabel Bulnes-Enriquez MD; Xochitl Jimenez MD; Roxana De La Rosa BS; Tamara Modilevsky MD; Katherine Yu MD; Yanjie Li MD; Kent D. Taylor PhD; Willa A. Hsueh MD; Howard N. Hodis MD; and Jerome I. Rotter MD

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.

^* To whom correspondence should be addressed. 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

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