Mutation analysis of seven SLC family transporters for early-onset Parkinson's disease in Chinese population

Abstract

The solute carrier (SLC) transporters have been suggested to play important roles in neurodegenerative disorders. Recently, seven SLC transporters were identified to be associated with Parkinson's disease (PD) by genome-wide association studies. However, few replications were conducted, and whether rare variants in these genes were associated with PD was not explored yet. To elucidate the genetic associations of these SLCs with PD, we investigated the rare variants in 743 Chinese early-onset PD (EOPD) patients using whole-exome sequencing, and evaluated the association between rare variants and PD at allele and gene levels. Totally, 58 rare variants were identified in SLC50A1, SLC41A1, SLC45A3, SLC44A4, SLC56A2, SLC2A13 and SLC38A1. At allele level, 6 variants were nominally associated with PD, namely p.S423G in SLC45A3, p.I551V, p.T435S, p.R323C and p.V101M in SLC2A13, and p.R285Q in SLC41A1. Gene-based burden analysis showed enrichment of rare variants of SLC2A13 in EOPD. Our study systematically analyzed the genetic involvement of SLCs in EOPD, identified SLC2A13 as a risk gene for PD, and broadened the current mutation spectrum of PD.