BST1 rs4698412 allelic variant increases the risk of gait or balance deficits in patients with Parkinson’s disease

Abstract

Summary Aims We aimed to explore effects of bone marrow stromal cell antigen‐1 (BST1) rs4698412 allelic variant on brain activation and associative clinical symptoms in Parkinson’s disease (PD). Methods A total of 49 PD patients and 47 healthy control (HC) subjects were recruited for clinical evaluations, blood samples collection for genotypes, and resting‐state functional MRI (rs‐fMRI) scans. Based on BST1 rs4698412 allelic variant (G → A), participants were further divided into 18 PD‐GG, 31 PD‐GA/AA, 20 HC‐GG, and 27 HC‐GA/AA carriers, which respectively indicated subjects carrying ancestral or risk allele in that locus in PD or HC. Two‐way analysis of covariance (ANCOVA) was applied to investigate main effects and interactions between PD and BST1 rs4698412 allelic variant on brain function via amplitude of low‐frequency fluctuations (ALFF). Spearman’s correlations were then utilized to detect associations between interactive brain regions and clinical symptoms. Results Compared to HC subjects, PD patients exhibited increased ALFF values in left cerebellum_8 and cerebellum_9. Significant interaction was in right lingual gyrus, where there were the lowest ALFF values and ALFF values were only negatively associated with Timed Up and Go (TUG) test time in PD‐GA/AA subgroup. Conclusion BST1 rs4698412‐modulated lingual gyrus functional alterations could be related to gait and balance dysfunction in PD.

Clinical or neuroimaging profiles in the assessment of genetic variants associated with neurodegenerative diseases

“…In this issue of CNS Neuroscience & Therapeutics, Shen et al report a study aiming to observe the functional effect of a variant identified in GWAS in patients with Parkinson's disease (PD). The study belongs to the field of neuroimaging genetics, which has grown rapidly in recent years and whose application to neurodegenerative diseases may be a key to improving our knowledge of the function of certain genetic variants.…”

“…Likewise, this is not the only variant of the BST1 gene observed in GWAS studies (Table ); however, given the noncoding character of these variants and the hypothesis that they act on a regulatory network, a shared mechanism may be involved . Shen et al analyze the pathogenicity of this variant, attempting to identify a specific clinical and functional neuroimaging profile in patients, according to the allelic variant of the gene. Other authors have previously attempted to establish a relationship between the disease and presence of the variant using the Unified Parkinson's Disease Rating Scale and the Hoehn‐Yahr Stage, but rs4698412 was excluded from the analysis for methodological reasons …”

“…The study by Shen et al is one of few studies that attempt to validate the detected variants through profiles and the first to include rs4698412. The authors observe a clinical profile associated with gait deficits and a functional magnetic resonance imaging profile that suggests that BST1 variants may affect stability in patients with PD.…”

“…The authors observe a clinical profile associated with gait deficits and a functional magnetic resonance imaging profile that suggests that BST1 variants may affect stability in patients with PD. Regardless of whether these data should be reproduced, the findings of Shen et al support the idea that the variants identified in genetic association studies should be systematically validated by studying clinical profiles and, in the case of such neurodegenerative diseases as PD, neuroimaging profiles; data from these profiles should therefore be considered when analyzing the pathogenicity of these variants. Therefore, observing a higher frequency among patients of a variant whose incidence is high in the general population must be accompanied by other criteria if we are to consider that it has a role in the development of a disease, whether in its incidence or its progression.…”

Dysfunction in superior frontal gyrus associated with diphasic dyskinesia in Parkinson’s disease

“…Participants were scanned using a 3.0 T Siemens MAGNETOM Verio whole-body MRI scanner (Siemens Medical Solutions, Germany), as described in our previous studies 45 , 46 . Tight foam padding was used to minimize head movement and ear-plugs were used to reduce noise.…”