Association study between the LINGO1 gene and Parkinson's disease in the Italian population

Abstract

Some studies have suggested an overlap of clinical and genetic findings between essential tremor (ET) and Parkinson's disease (PD). The first genome-wide association study in ET showed a significant association with the rs9652490 SNP of the leucine-rich repeat and Ig domain containing 1 (LINGO1) gene. Since patients with PD have higher LINGO1 expression levels compared to healthy controls, and animal models of PD show elevated LINGO1 protein levels after experimentally induced damage in the striatum, it can be inferred that LINGO1 is probably involved in PD pathophysiology. In this study, we performed a genetic association analysis of the rs9652490 and rs11856808 SNPs in Italian PD patients and controls to assess the role of these variants in our population. A total of 567 patients with PD and 468 control subjects were enrolled in five Movement Disorder centers located in Central-Southern Italy. Both variants were significantly associated with PD under a recessive model of inheritance before applying the Bonferroni correction. The GG genotype of rs9652490 and the TT genotype of rs11856808 were less frequent in patients than in controls, suggesting a protective effect against the disease. However, after stringent correction, only the P-values obtained from allele and genotype comparisons of the rs11856808 SNP remained significant. Our findings suggest that LINGO1 plays a certain role in the development of PD in the Italian population and represents an interesting candidate gene responsible for PD, due to its involvement in neurological processes.