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Arterioscler Thromb Vasc Biol. 2009 Jan;29(1):47-53. doi: 10.1161/ATVBAHA.108.178111. Epub 2008 Oct 23.

Genetic modifier loci linked to intima formation induced by low flow in the mouse carotid.

Author information

1
Aab Cardiovascular Research Institute, 601 Elmwood Avenue, Rochester, NY 14642, USA. Slava_Korshunov@URMC.rochester.edu

Abstract

OBJECTIVE:

Previously we found dramatic strain-dependent differences in a low flow model of vascular remodeling. Specifically, intima formation in the left common carotid artery was approximately 30-fold greater in SJL compared to C3HeB/Fe (C3H/F) mice. We hypothesized that a few genes control intima formation in response to low flow. A C3H/F and SJL backcross resulted in broad range of N2 intima phenotypes.

METHODS AND RESULTS:

Using genome-wide scan we identified two highly significant quantitative trait loci (QTLs) for intima, Im1 (intima modifier 1 locus) on chromosome 2 (Chr2; 77.6 cM, LOD=6.4), and Im2 on Chr11 (17 cM, LOD=5.3). One significant QTL Im3 was found on Chr18 (6 cM, LOD=3.0), and two suggestive QTLs (LOD=1.5 and 1.8) were identified on Chr7 and Chr17, respectively. Interestingly, the intima/media ratio trait mapped to the same QTLs as the intima trait. Haplotype mapping predicted 40 candidate genes. Six of these genes contained SNPs that differed between C3H/F and SJL.

CONCLUSIONS:

We have successfully mapped 3 QTLs (Im1, Im2, and Im3) that are associated with carotid intima formation in response to low blood flow. These results may be important in identifying genes that influence carotid intima-media thickening and predict cardiovascular disease in humans.

PMID:
18948632
PMCID:
PMC2746566
DOI:
10.1161/ATVBAHA.108.178111
[Indexed for MEDLINE]
Free PMC Article

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