Association of a Vcam1 mutation with atherosclerosis susceptibility in diet-induced models of atherosclerosis

Toru Miyoshi, Zuobiao Yuan, Weibin Shi

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

We previously identified a G > A single nucleotide polymorphism (SNP) between C57BL/6J (B6) and C3H/HeJ (C3H) mouse strains at position 2077 in the coding region of Vcam1 that leads to substitution of an amino acid from aspartic acid (D) to asparagine (N) in the protein product. In the present study, we investigated the association of this SNP with atherosclerosis susceptibility using a panel of inbred mouse strains, a set of recombinant inbred (RI) strains derived from B6 and C3H mice, and a cohort of F2 mice derived from B6 and C3H apolipoprotein E-deficient (apoE-/-) mice. Inbred strain analysis revealed that mouse strains with the B6 Vcam1 genotype developed significantly larger atherosclerotic lesions than strains with the C3H genotype (4622 ± 2816 μm2/section versus 362 ± 697 μm2/section; P = 0.029). BXH RI strains with the B6 Vcam1 genotype also developed larger atherosclerotic lesions than those with the C3H genotype (8305 ± 9031 μm2/section versus 2139 ± 2931 μm2/section) although the difference was not statistically significant (P = 0.13). In contrast, no association was detected between Vcam1 and atherosclerotic lesion size in F2 mice. The present data indicate that the G > A mutation of Vcam1 is associated with atherosclerotic lesion formation in the dietary but not apoE-/- models of atherosclerosis and this association suggests a role for the Vcam1 gene in influencing atherosclerosis susceptibility.

Original languageEnglish (US)
Pages (from-to)234-239
Number of pages6
JournalAtherosclerosis
Volume196
Issue number1
DOIs
StatePublished - Jan 2008
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health grants HL71844 and HL75433. The authors thank Jessica Rowlan for critically reviewing the manuscript.

Keywords

  • Atherosclerosis
  • Mouse
  • Single nucleotide polymorphism
  • Vcam1

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