December 26, 2007

Study Shows DPP6 Variant An ALS Risk Factor

A specific variation in a gene known as DPP6 is significantly associated with susceptibility to amyotrophic lateral sclerosis (ALS) in a large group of people of European ancestry, according to a new study published online Dec. 16 in Nature Genetics.

When Leonard van den Berg at University Medical Center in Utrecht, the Netherlands, with colleagues in that country, as well as Belgium, Sweden and the United States, studied the DNA of 1,767 people with ALS and 1,916 without the disease, they found that those with the disease were 1.3 times more likely than the unaffected subjects to have this particular DPP6 gene variant.

U.S.-based researchers in the group included Jennifer Schymick and Bryan Traynor of the National Institutes of Health in Bethesda, Md., and Roel Ophoff of the University of California-Los Angeles.

The study participants were from the Netherlands, Sweden and Belgium.

DPP6 is located on chromosome 7 and carries instructions for a protein found mostly in the brain, where it modifies the biological activity of several nervous-system chemicals (neuropeptides) and alters a mechanism that controls potassium flow.

ALS is thought to be clearly inherited (familial) only about 10 percent of the time, but most experts in the disease believe that genetic factors alter susceptibility to nonfamilial, or sporadic, ALS.

Efforts to find these factors have led to several “whole-genome association” studies, in which all the DNA from ALS-affected subjects is compared with all the DNA from unaffected subjects to see whether there are significant differences.

A recent study conducted at the NIH failed to find any. However, this past August, an MDA-supported study conducted at the Translational Genomics Research Institute in Phoenix identified a variant in a gene called FLJ10986 as a significant contributor to ALS susceptibility in a large sample of Americans with and without the disease.