Positional identification of TNFSF4, encoding OX40 ligand, as a gene that influences atherosclerosis susceptibility

Xiaosong Wang, Massimiliano Ria, Peter M. Kelmenson, Per Eriksson, David C. Higgins, Ann Samnegård, Christina Petros, Jarod Rollins, Anna M. Bennet, Björn Wiman, Ulf De Faire, Charlotte Wennberg, Per G. Olsson, Naoto Ishii, Kazuo Sugamura, Anders Hamsten, Kristina Forsman-Semb, Jacob Lagercrantz, Beverly Paigen

Research output: Contribution to journalArticlepeer-review

246 Citations (Scopus)

Abstract

Ath1 is a quantitative trait locus on mouse chromosome 1 that renders C57BL/6 mice susceptible and C3H/He mice resistant to diet-induced atherosclerosis. The quantitative trait locus region encompasses 11 known genes, including Tnfsf4 (also called Ox40I or Cd134I), which encodes OX40 ligand. Here we report that mice with targeted mutations of Tnfsf4 had significantly (P ≤ 0.05) smaller atherosclerotic lesions than did control mice. In addition, mice overexpressing Tnfsf4 had significantly (P ≤ 0.05) larger atherosclerotic lesions than did control mice. In two independent human populations, the less common allele of SNP rs3850641 in TNFSF4 was significantly more frequent (P ≤ 0.05) in individuals with myocardial infarction than in controls. We therefore conclude that Tnfsf4 underlies Ath1 in mice and that polymorphisms in its human homolog TNFSF4 increase the risk of myocardial infarction in humans.

Original languageEnglish
Pages (from-to)365-372
Number of pages8
JournalNature Genetics
Volume37
Issue number4
DOIs
Publication statusPublished - 2005 Apr

ASJC Scopus subject areas

  • Genetics

Fingerprint Dive into the research topics of 'Positional identification of TNFSF4, encoding OX40 ligand, as a gene that influences atherosclerosis susceptibility'. Together they form a unique fingerprint.

Cite this