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Advanced Neurologyurology
Advanced Ne Genetics in PD hyposmia

normal in some cases long after motor symptoms onset . hyposmia by the item in NMSQ, “Loss or change in your
[5]
The detailed mechanism that contributes to the differences ability to taste or smell” . PD individuals with taste
[15]
in olfactory function in individuals is yet to be clarified; dysfunction were excluded from the study.
therefore, numerous studies focusing on the underlying
genetic variations of olfactory function in PD patients have 2.3. High-throughput sequencing
been conducted [6-8] . Genomic DNA of 203 individuals was extracted from the
Interestingly, a recent whole-genome sequencing peripheral blood using the QIA ampDNA Blood Maxi
analysis revealed that variants in OR6C70 (encoding the Kit (QIAGEN, Valencia, CA, USA). Then, whole-exome
olfactory receptor family six subfamily C member 70) and sequencing was performed as described in our previous
TAAR5 (encoding the trace amine associated receptor 5) study [16,17] . TAAR5, OR6C70, and GBA were included in
affect the different perceptions of specific odors between our genotype analysis. Single nucleotide polymorphisms
different individuals. Genetic variations in these two (SNPs) and insertions/deletions (Indels) located within
genes may partially underlie the olfactory recognition the exons and exon-intron boundaries of these three genes
[17]
differences . To date, these conclusions have not been were then identified as described previously . After
[6]
replicated in other studies or populations. To our concern, variants calling and annotation, the data were compared
PD is a disease well associated with olfactory dysfunction. to our in-house data to distinguish between common and
[16]
Whether the aforementioned gene variants contribute to rare variants . To achieve adequate statistical power,
[16]
the differences in olfactory function of PD individuals we excluded rare variants . Linkage disequilibrium was
[18]
remains unclear. In our study, we aimed to explore the estimated using SHEsis (offline version) , and SNPs with
2
potential association of OR6C70 and TAAR5 with hyposmia r ≥ 0.80 were defined as being in linkage disequilibrium.
in Han Chinese individuals with PD. In addition, GBA 2.4. Statistical analysis
(glucocerebrosidase gene, a common PD causative gene)
was also included in this study since previous studies have In univariate analysis, Kolmogorov–Smirnov test or
demonstrated that some PD individuals with mutations in Shapiro–Wilk test was used to test if the variables were
GBA have reported hyposmia [8,9] . normally distributed in 203 PD individuals. Differences in
age, duration, UPDRS-III score, and other variables between
2. Materials and methods hyposmia and non-hyposmia groups were compared using
Student’s t-test (when they were normally distributed) or
2.1. Subjects
non-parametric Mann–Whitney U-test (when they were
Two hundred and three Han Chinese individuals with not normally distributed). Gender and other dichotomous
PD, who fulfilled either the 2015 Movement Disorder variables were compared with Chi-square test or Fisher’s
Society clinical diagnostic criteria or the UK Brain Bank exact test. Binary logic regression to hyposmia was used to
[10]
criteria for PD, were recruited consecutively from the explore the potential associated factors.
[11]
Department of Neurology of the Second Affiliated Hospital Associations were quantified with the odds ratio (OR)
of Soochow University (Suzhou, China) from January and 95% confidence intervals (CIs). All statistical tests
2013 to December 2019. Individuals with severe cognitive were two-sided, and P < 0.05 was considered statistically
impairment who cannot cooperate with the assessment significant. All tests were performed using IBM SPSS
were excluded from the study. Our study was approved Statistics, version 25.0 (IBM Corporation, NY, USA).
by the ethics committee of the Second Affiliated Hospital
of Soochow University (JD-LK-2018-061-01). Detailed 3. Results
clinical data and blood samples were collected after written
informed consent were obtained from all the participants. Of 203 PD individuals, 118 (58.1%) reported hyposmia, and
85 (41.9%) reported normal olfactory function. According
2.2. Clinical assessment to the demographic analysis, male individuals with and
The demographics, including age, age at onset, duration and without hyposmia were 76 (57.6%) and 49 (64.4%),
gender, of enrolled PD individuals were recorded. Disease respectively. We did not find any significant differences in
severity was assessed by the Unified Parkinson Disease the demographic profiles between PD individuals with and
Rating Scale (UPDRS) Part III during the “on” state. without hyposmia; these demographic parameters include
[12]
Prescribed levodopa equivalent doses of dopaminergic gender, age, age of onset, duration, disease severity, and
medication were calculated according to the protocol . prescribed dopaminergic medication dose (Table 1).
[13]
Non-motor symptoms (NMSs) were assessed by the Non- In our genotype analyses, we found 91 SNPs and 0 Indel
Motor Symptoms Questionnaire (NMSQ) . We defined within the exons and exon-intron boundaries of OR6C70,
[14]

Volume 1 Issue 2 (2022) 2 https://doi.org/10.36922/an.v1i2.71