DPP6 gene variability confers increased risk of developing sporadic amyotrophic lateral sclerosis in Italian patients

Amyotrophic lateral sclerosis (ALS) is an adult onset neurodegenerative disease characterised by progressive loss of motor neurons. Approximately 5% of cases of ALS are familial, with the remaining being sporadic. Although the aetiology of sporadic ALS (SALS) is largely unknown, familial and epidemiological data indicate that genetic factors may contribute to its pathogenesis. To date, a number of modifier loci and associated genes have been implicated and several polymorphic variants have been proposed as risk factors for developing SALS.1 Despite this, no single gene has been definitively shown to cause SALS as attempts to replicate positive findings in different populations have often failed. For example, more recently, replication failed to associate vascular endothelial growth factor or angiogenin across populations with different genetic background, including an Italian population.2 Lack of replication and/or small effects of associated alleles are obvious problems in the understanding of a complex and genetically heterogeneous disorder such as SALS. However, it has been demonstrated recently that the variant rs10260404 within the DPP6 gene is strongly associated with susceptibility to ALS across different populations of European ancestry (from The Netherlands, Belgium and Sweden) as well as in a cohort of American patients (a combined sample of 1767 cases and 1916 healthy controls was included).3 The aim of the present study was to investigate the above identified genetic variant as a possible risk factor for developing SALS in an Italian population.