Angiogenin Gene Mutations
Likely Boost ALS Susceptibility

Mutations in the gene for angiogenin (ANG), a protein that aids in the formation of new blood vessels, is a new suspect in amyotrophic lateral sclerosis (ALS) susceptibility, say members of a multinational research group who published their findings online Feb. 26 in Nature Genetics.

The team, led by Matthew Greenway and Orla Hardiman at the Royal College of Surgeons in Dublin, Ireland, included Robert Brown, professor of neurology and director of the MDA/ALS Center at Massachusetts General Hospital in Boston.

In a study of 1,629 people with ALS and 1,265 without ALS, the investigators identified seven genetic mutations (alterations) in the ANG gene in four people with familial ALS and 11 with no family history of the disease (sporadic ALS). Twelve of the 15 were of Irish or Scottish descent. Only one person, a 65-year-old man, had an ANG mutation without having ALS.

Angiogenin resembles another protein, vascular endothelial growth factor (VEGF), in that both cause the formation of new blood vessels in response to a low-oxygen environment. Unusually low levels of VEGF have been implicated as a possible factor in ALS.

The ANG gene variations may be risk factors only in some populations, Brown says, although they still may be important. “The caveat from the VEGF story is that those variants were found to be highly related to sporadic ALS only in the Belgian population,” he says. “This has not been reproduced in other populations.”

The presence of an ANG risk factor without ALS in one person “tells you that it can occur in normals,” he says, “but it’s certainly overrepresented in ALS and certainly significantly overrepresented in the population of Ireland and Scotland.”

These types of variations are being sought on a large scale through an MDA-funded project at the Translational Genomics Research Institute in Phoenix.