Kouichi Ozaki at RIKEN’s Center for Genomic Medicine in Yokohama and co-workers have identified small changes in a gene called BRAP that can greatly increase the risk of heart attacks in Asian people1.
A heart attack, technically known as myocardial infarction (MI), is a sudden interruption of the blood supply to the heart. Scientists have been searching for genetic markers of the condition, which may be as small as single nucleotide polymorphisms (SNPs)—genetic variations that are commonly present in our genome.
“There are several reports associating MI with many SNPs, however most of these reports were conducted with small samples,” says Ozaki. “In 2001, we started genome-wide association studies using nearly 90,000 gene-based SNPs, and identified several genes … that confer risk of MI.”
One of these genes, called LGALS2, codes for a protein called galectin-2. Ozaki and co-workers searched for proteins that interact with galectin-2, and identified BRAP protein as a possible binding partner.
They found 26 previously unknown SNPs in the BRAP gene, and counted how often these SNPs occurred in the genomes of 2,475 Japanese MI sufferers and 2,778 control subjects. This process revealed two particular SNPs that were very strongly linked to MI.
The link was confirmed in another Japanese dataset and a dataset from Taiwan. However, the two critical SNPs were not found in datasets from North America or Africa, implying that they may be unique to Asian populations (Fig. 1).
“The results indicate that these SNPs are likely to be present only in Asian populations,” says Ozaki. “However, the possibility cannot be excluded that different variations in this gene confer risk of MI in other populations.”
The BRAP protein was found alongside galectin-2 in both the cytoplasm and nucleus of human coronary artery muscle cells. It was also expressed in myocardial lesions—abnormal tissue growth in the artery caused by a massive inflammatory response.
“The function of galectin-2 is largely unknown,” says Ozaki. “However, we found that galectin-2 binds to and regulates secretion of lymphotoxin-alpha, a proinflammatory cytokine produced in an early stage of vascular inflammation. Considering that it also interacts with BRAP protein, galectin-2 may be a key player in the vascular inflammatory system.”
The study opens the question of whether scientists could eventually alter individual SNPs in a genome in order to prevent conditions like myocardial infarction.
“It is impossible with present technologies and ethics,” says Ozaki. “However, innovative technologies might be developed in the future.”
Reference
Ozaki, K., Sato, H., Inoue, K., Tsunoda, T., Sakata, Y., Mizuno, H., Lin, T.-H., Miyamoto, Y., Aoki, A., Onouchi, Y. et al. SNPs in BRAP associated with risk of myocardial infarction in Asian populations. Nature Genetics 41, 329–333 (2009).
The corresponding author for this highlight is based at the RIKEN Laboratory for Cardiovascular Diseases
