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Advanced Neurology Genetics in PD hyposmia

TAAR5, and GBA. We did not find the previously reported Table 1. Demographic profiles of PD individuals with/
rare TAAR5 p.Ser95Pro mutation in any of the individuals. without hyposmia
Eighty-three of the 91 SNPs were rare variants (minor allele Non‑hyposmia Hyposmia P*
frequency < 0.10) and were excluded from subsequent (n=85) (n=118)
analysis for better statistical power. Finally, eight common Gender (male, %) 49 (57.6%) 76 (64.4%) 0.381
SNPs (TAAR5 rs3813355, rs3813354; OR6C70 rs60683621;
GBA rs1800473, rs762488, rs2009578, rs2974923, and Age (year) 60.59±11.78 63.00±9.22 0.212
rs1800438) and 0 Indel were included in our association Age of onset (year) 56.18±12.74 57.85±9.18 0.598
analyses and none of them was in linkage disequilibrium. Duration (month) 52.58±42.42 61.47±53.66 0.471
In our genotype logistic regression analyses to hyposmia, LED 420.36±250.73 446.71±255.68 0.535
considering age, gender, duration, motor symptoms and UPDRS-III 20.26±10.40 23.25±13.81 0.153
other demographics, we found that none of the SNPs was LED, Levodopa equivalent dose; PD, Parkinson’s disease; UPDRS-III,
associated with hyposmia (Table 2). Unified Parkinson’s Disease Rating Scale – Part III. *Mann–Whitney
In our allele logistic regression analyses to hyposmia, U-test
considering age, gender, duration, motor symptoms and
other demographics, we did not find the three common Table 2. Genotype logistic regression analysis of hyposmia in
SNPs in TAAR5 and OR6C70 being significantly associated 203 PD individuals
with hyposmia. However, we found that GBA rs762488 Regression coefficient P* OR 95% CI
was associated with increased hyposmia risk (P = 0.036, Gender (male, %) −0.382 0.220 0.68 0.37–1.26
OR = 3.05, 95% CI = 1.08–8.63), and GBA rs1800438 Age (year) −0.028 0.949 0.97 0.41–2.28
was associated with decreased hyposmia risk (P = 0.032,
OR = 0.47, 95% CI = 0.24–0.94) (Table 3). Age of onset (year) 0.054 0.902 1.05 0.45–2.47
Duration (month) 0.008 0.834 1.01 0.94–1.08
4. Discussion LED 0.000 0.711 1.00 1.00–1.00
PD is the second most common neurodegenerative UPDRS-III 0.016 0.250 1.02 0.99–1.04
disease with many motor and non-motor symptoms [19,20] . rs3813355 0.344 0.202 1.41 0.83–2.39
Hyposmia is one of the core non-motor symptoms of rs3813354 −0.134 0.655 0.87 0.49–1.57
PD and is part of the critical clinical diagnostic criteria rs60683621 0.109 0.603 1.12 0.74–1.68
for PD . Nevertheless, hyposmia is a condition with rs1800473 −0.378 0.340 0.69 0.32–1.49
[10]
incomplete penetrance and different PD individuals with
hyposmia may have a varying degree of olfactory loss [21-23] . rs762488 0.779 0.073 2.18 0.93–5.11
The detailed mechanism of hyposmia occurrence remains rs2009578 −0.390 0.244 0.68 0.35–1.31
undetermined. So far, there have been limited studies rs2974923 0.074 0.724 1.08 0.71–1.62
unraveling the specific genetic background of hyposmia in rs1800438 −0.412 0.105 0.66 0.40–1.09
PD. Since hyposmia is a prevalent non-motor symptom in CI, Confidence interval; LED, Levodopa equivalent dose; OR, Odds
PD, increasing attention has been devoted to investigating ratio; PD, Parkinson’s disease; UPDRS-III, Unified Parkinson’s Disease
olfaction in PD. Recently, Gisladottir et al. found that Rating Scale - Part III. *Logistic regression adjusted for gender, age, age
TAAR5 p.Ser95Pro mutation is associated with a reduced of onset, motor symptoms, LED, and UPDRS-III
intensity rating of fish odor containing trimethylamine .
[6]
TAAR5 is a G protein-coupled receptor, which shares 35% were not able to find any significant association between
of the sequence with 5-HT-1D receptor and 33% with hyposmia and common variants (including the reported
[24]
dopamine D2 receptor , which may contribute to PD rs60683621) in these two genes. We did not replicate the
[25]
pathology . Besides, Gisladottir et al. also found that reported association between rs60683621 and olfactory
[26]
OR6C70 p.Lys233Asn (rs60683621) is associated with function, which merely a consequence of global hyposmia
increased intensity and identification of licorice odor . assessment previously instead of an assessment scale with
[6]
However, the associations of OR6C70 and TAAR5 with PD specific olfactory domain evaluation in our study, which
have not been reported previously. Such results highlighted warrants further investigations in future studies.
that sequence diversity in olfactory receptor genes can lead GBA encodes glucocerebrosidase, a lysosomal protein
to enhanced olfactory ability. that cleaves the beta-glycosidic bond of glucosylceramide
In our study, the sequencing covered exon and exon- and contributes to Gaucher’s disease and PD. Thaler
intron boundary regions of TAAR5 and OR6C70, but we et al. and da Silva et al. found that mutations in GBA

Volume 1 Issue 2 (2022) 3 https://doi.org/10.36922/an.v1i2.71