Alpha-Synuclein mRNA Level Found Dependent on L444P Variant in Carriers and Gaucher Disease Patients on Enzyme Replacement Therapy
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients and Blood Samples
2.2. Biobanking
2.3. α-Synuclein mRNA Analysis
2.4. α-Synuclein Total and Oligomer Protein Concentration
2.5. Statistical Analysis
3. Results
3.1. Patients’ Characteristics
3.2. Lyso-Gb1 Concentration
3.3. SNCA Gene Expression
3.4. α-SNCA Total Protein Level
3.5. α-SNCA Oligomer Concentration
3.6. Correlations with Age
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Number of Patients | Common Variant Name | DNA Nucleotide Change | Protein Change |
---|---|---|---|
28 | N370S/L444P | c.1226A>G c.1448T>C | p.Asn409Ser p.Leu483Pro |
6 | N370S/ others | c.1226A>G | p.Asn409Ser |
2 | N370S/N370S | c.1226A>G | p.Asn409Ser |
2 | G377S/G377S | c.1246G>A | p.Gly416Ser |
1 | N370S/ G377S | c.1226A>G c.1246G>A | p.Asn409Ser p.Gly416Ser |
1 | N370S/84GG | c.1226A>G c.84dupG | p.Asn409Ser p.Leu29AlafsTer18 |
1 | N370S/R496H | c.1226A>G c.1604G>A | p.Asn409Ser p.Arg535His |
1 | R433S/R433S | c.1416A>T | p.Arg444Ser |
1 | D438N/R87W | c.1312G>A c.259C>T | p.Asp438Asn p.Arg87Trp |
1 | D448G/R202X | c.1343A>G c.604C>T | p.Asp448Gly p.Arg202X |
1 | R48W/84GG | c.259C>T c.84dupG | p.Arg87Trp p.Leu29AlafsTer18 |
1 | R48W/R48W | c.259C>T | p.Arg87Trp |
1 | 84GG/ Other | c.84dupG | p.Leu29AlafsTer18 |
Healthy Controls | GBA1 Mutation Carriers | GD1 | GD3 | |
---|---|---|---|---|
n | 16 | 19 | 47 | 18 |
Sex, F/M | 10/6 | 14/5 | 28/19 | 12/8 |
Age in years, median (range) | 44.5 | 52 (13–64) | 40 (9–71) | 30 (22–62) |
Lyso-Gb1 (ng/mL), median (range) | 8.49 (4.82–46.73) | 7.51 (4.26–46.73) | 71.5 (22.4–950.9) | 64.55 (9.14–693.8) |
SNCA mRNA level (2−ΔcT), median (range) | 0.83 (0.08–16.38) | 4.16 (0.02–161.42) | 0.47 (0.01–134.42) | 77.48 (0.04–141.72) |
Total α-SNCA concentration (ng/mL), median (range) | 1.34 (0.16–37.48) | 0.53 (0.16–21.76) | 0.16 (0.16–20) | 0.92 (0.16–20) |
Oligomer α-SNCA concentration (ng/mL), median (range) | 2.08 (0.96–4.73) | 1.69 (1.03–3.33) | 1.76 (0.76–4.01) | 1.857(0.76–3.03) |
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Dubiela, P.; Szymańska-Rożek, P.; Eljaszewicz, A.; Lipiński, P.; Hasiński, P.; Giersz, D.; Walewska, A.; Tynecka, M.; Moniuszko, M.; Tylki-Szymańska, A. Alpha-Synuclein mRNA Level Found Dependent on L444P Variant in Carriers and Gaucher Disease Patients on Enzyme Replacement Therapy. Biomolecules 2023, 13, 644. https://doi.org/10.3390/biom13040644
Dubiela P, Szymańska-Rożek P, Eljaszewicz A, Lipiński P, Hasiński P, Giersz D, Walewska A, Tynecka M, Moniuszko M, Tylki-Szymańska A. Alpha-Synuclein mRNA Level Found Dependent on L444P Variant in Carriers and Gaucher Disease Patients on Enzyme Replacement Therapy. Biomolecules. 2023; 13(4):644. https://doi.org/10.3390/biom13040644
Chicago/Turabian StyleDubiela, Paweł, Paulina Szymańska-Rożek, Andrzej Eljaszewicz, Patryk Lipiński, Piotr Hasiński, Dorota Giersz, Alicja Walewska, Marlena Tynecka, Marcin Moniuszko, and Anna Tylki-Szymańska. 2023. "Alpha-Synuclein mRNA Level Found Dependent on L444P Variant in Carriers and Gaucher Disease Patients on Enzyme Replacement Therapy" Biomolecules 13, no. 4: 644. https://doi.org/10.3390/biom13040644