To try to identify the pathogenic genes involved in ALS, the Umeå scientists, in collaboration with Dutch and Belgian researchers, compared DNA samples from 1,337 patients with non-hereditary ALS (sporadic ALS, SALS) with DNA samples from 1,356 healthy individuals.
It is the world’s most comprehensive study in the field thus far. The researchers looked for DNA variants that only occur in patients and not in control subjects. After extremely extensive analyses, they discovered that such a variant in the gene Inositol 1,4,5-triphosphate receptor 2 (ITPR2) is strongly associated with SALS.
The ITPR2 gene codes for a protein that is important to the regulation of calcium levels in nerve cells. The protein is also involved in neurotransmission (communication between nerve cells) and so-called programmed cell death. Blood analyses revealed that the gene’s activities are higher in ALS patients than in healthy subjects.
Taken together, this indicates that changes in the ITPR2 gene are a strong candidate to be seen as a risk factor in developing ALS.
The research team is now busy looking for disease-related mutations in the gene. It is completely unknown just how mutations in the ITPR2 can lead to ALS. At present it is not possible to determine whether the discovery will lead to any new treatment of ALS.
The Swedish part of the study was performed by Associate Professor and Chief Physician Peter M. Andersen, molecular geneticist Anna Birve, and research engineer Ann-Charloth Nilsson, all at the Department of Pharmacology and Clinical Neuroscience, Umeå University.
The discovery will be published in The Lancet Neurology in October. The Lancet Neurology is the leading international journal on diseases of the brain.
Reference: Michael A van Es, Paul W Van Vught, Hylke M Blauw, Lude Franke, Christiaan G Saris, Peter M Andersen, Ludo Van Den Bosch, Sonja W de Jong, Ruben van t Slot, Anna Birve, Robin Lemmens, Vianney de Jong, Frank Baas, Helenius J Schelhaas, Kristel Sleegers, Christine Van Broeckhoven, John H Wokke, Cisca Wijmenga, Wim Robberecht, Jan H Veldink, Roel A Ophoff, Leonard H van den Berg: ITPR2 as a susceptibility gene in sporadic amyotrophic lateral sclerosis: a genome-wide association study.