Association analysis of polymorphisms in VMAT2 and TMEM106B genes for Parkinson's disease, amyotrophic lateral sclerosis and multiple system atrophy.

BACKGROUND: The vesicular monoamine transporter type 2 (VMAT2) and transmembrane Protein 106B (TMEM106B) were reported to be associated with neurodegenerative diseases. Recent studies found that two polymorphisms (rs363371 and rs363324) in VMAT2 might be a risk factor for Parkinson's disease (PD) in Caucasians, while the two other variants (rs1990622 and rs3173615) in TMEM106B increased the risk for frontotemporal dementia (FTD). Considering the overlap between clinical manifestation and pathologic characteristics in neurodegenerative diseases, we conducted a large-sample study to investigate the associations between these four polymorphisms and the risk for PD, sporadic amyotrophic lateral sclerosis (SALS), and multiple system atrophy (MSA) in a Chinese patient population.

METHODS: A total of 1121 PD, 863 SALS, and 356 MSA patients, as well as 829 healthy controls (HCs), were included in the study. These four polymorphisms were genotyped using Sequenom iPLEX Assay technology.

RESULTS: Significant differences were found in the genotype distribution of VMAT2 rs363371 between SALS patients and HCs (p=0.001). In an additive model, "GG" of rs363371 significantly decreased the risk for SALS (p<0.001, OR: 0.49, 95% CI [0.36-0.67]). The frequencies of minor alleles for rs1990622 and rs3173615 in TMEM106B were significantly different between PD patients with initial symptoms of tremor and rigidity/bradykinesia (p=0.001), and between patients with initial symptom of rigidity/bradykinesia and HCs (p<0.001). The minor alleles "T" of rs1990622 and "C" of rs3173615 increased the risk for PD patients with initial symptom of rigidity/bradykinesia (OR: 1.21[1.10-1.34] and OR: 1.19[1.07-1.31], respectively). No differences were found in the genotype distribution and allele frequency of the four polymorphisms between MSA patients and HCs.

CONCLUSION: In this Chinese patient population, "GG" of rs363371 in VMAT2 may reduce the risk for SALS, while minor alleles of rs1990622 and rs3173615 in TMEM106B may be associated with PD patients with initial symptom of rigidity/bradykinesia.