Determining the Effect of the HNMT, STK39, and NMD3 Polymorphisms on the Incidence of Parkinson’s Disease, Amyotrophic Lateral Sclerosis, and Multiple System Atrophy in Chinese Populations

Yongping Chen, Bei Cao, Ruwei Ou, Qianqian Wei, Xueping Chen, Bi Zhao, Ying Wu, Wei Song, Hui-Fang Shang

Large-scale meta-analyses of genome-wide association studies have identified several loci linked to sporadic Parkinson's disease (PD). However, the roles of some important loci, such as HNMT Thr105Ile, STK39 rs2390669, and NMD3 rs34016896, have not been clarified in Chinese populations. Accumulating evidence indicates that some common clinicopathological characteristics are shared by different neurodegenerative diseases. Consequently, we conducted a large sample study to investigate associations between these variants and PD, multiple system atrophy (MSA), and amyotrophic lateral sclerosis (ALS) in Chinese populations. A total of 2417 patients, including 1237 PD, 850 SALS, and 330 MSA patients, along with 836 healthy controls (HCs) were examined in this study. All patients were genotyped for SNPs using the Sequenom iPLEX assay. No significant differences were found in the genotype and allele frequency distributions between the three neurodegenerative diseases and three candidate variants investigated. In subgroup analysis, compared with PD patients with initial symptom of tremor and HCs, the minor allele frequency of NMD3 rs34016896 in PD patients with initial symptoms of rigidity/bradykinesia was significantly lower. In addition, female patients carrying the rs34016896 minor allele had an increased risk of developing MSA (OR 1.25, 95% CI [1.09-1.43]), and ALS patients carrying the Ile105 polymorphism on the Thr105Ile allele in the HNMT gene exhibited a trend toward a delay in symptom onset of 3.010 ± 1.629 years. Our results indicate that the presence of the rs34016896 allele in the NMD3 gene may contribute to the development of synucleinopathies and that the Thr105Ile allele in the HNMT gene could potentially be an important therapeutic target for the treatment of ALS.