Alzheimer’s Disease Risk Variant rs3865444 in the CD33 Gene: A Possible Role in Susceptibility to Multiple Sclerosis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Subjects
2.2. Genotyping
2.3. Statistical Analysis
3. Results
3.1. Characteristics of Study Subjects
3.2. Association of CD33 rs3865444 with MS Risk
3.3. Association of CD33 rs3865444 with Clinical Phenotypes
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Parameter | Controls (n = 1145) | MS Total (n = 579) | p-Value | MS Females | MS Males | p-Value |
---|---|---|---|---|---|---|
(n = 403) | (n = 176) | |||||
Age (years) | 51.86 ± 21.09 | 41.61 ± 10.51 | <0.0001 | 41.84 ± 10.46 | 41.08 ± 10.62 | 0.26 |
Age of onset (years) | - | 29.68 ± 9.78 | - | 29.63 ± 9.60 | 29.80 ± 10.21 | 0.87 |
Sex (females/males) | 717/428 | 403/176 | 0.0041 | - | - | - |
MS course (RR/SP) | - | 511/68 | - | 358/45 | 153/23 | 0.51 |
MS duration (years) | - | 11.91 ± 7.13 | - | 12.19 ± 7.11 | 11.26 ± 7.15 | 0.059 |
EDSS | - | 3.56 ± 1.56 | - | 3.56 ± 1.47 | 3.58 ± 1.76 | 0.71 |
MSSS | - | 4.41 ± 2.09 | - | 4.33 ± 1.97 | 4.60 ± 2.32 | 0.19 |
HLA-DRB1*15:01 positivity | 230 (20.09%) | 298 (51.47%) | <0.0001 | 214 (53.10%) | 84 (47.73%) | 0.23 |
Allele/Genotype | MS (n = 579) | Controls (n = 1145) | Genetic Model | Logistic Regression Analysis | |
---|---|---|---|---|---|
p-Value | OR (95% CI) | ||||
Allele contrast (A vs. C) | 0.68 | 0.97 (0.83–1.13) | |||
C | 806 (69.60%) | 1578 (68.91%) | Codominant (CA vs. CC) | 0.45 | 0.91 (0.73–1.15) |
A | 352 (30.40%) | 712 (31.09%) | Codominant (AA vs. CC) | 0.97 | 1.00 (0.68–1.46) |
CC | 285 (49.22%) | 538 (46.99%) | Dominant (AA + CA vs. CC) | 0.52 | 0.93 (0.75–1.16) |
CA | 236 (40.76%) | 502 (43.84%) | Recessive (AA vs. CA + CC) | 0.83 | 1.04 (0.72–1.50) |
AA | 58 (10.02%) | 105 (9.17%) | Over-dominant (CA vs. CC + AA) | 0.43 | 0.91 (0.73–1.14) |
Log-additive | 0.69 | 0.97 (0.82–1.14) |
Allele/Genotype | MS | Controls | Genetic Model | Logistic Regression Analysis | |
---|---|---|---|---|---|
p-Value | OR (95% CI) | ||||
HLA-DRB1*15:01-positive cohort | |||||
Allele contrast (A vs. C) | 0.14 | 0.82 (0.63–1.07) | |||
C | 424 (71.14%) | 308 (66.96%) | Codominant (CA vs. CC) | 0.028 | 0.64 (0.44–0.95) |
A | 172 (28.86%) | 152 (33.04%) | Codominant (AA vs. CC) | 0.62 | 0.85 (0.44–1.64) |
CC | 154 (51.68%) | 99 (43.04%) | Dominant (AA + CA vs. CC) | 0.040 | 0.68 (0.47–0.98) |
CA | 116 (38.93%) | 110 (47.83%) | Recessive (AA vs. CA + CC) | 0.89 | 1.04 (0.55–1.97) |
AA | 28 (9.39%) | 21 (9.13%) | Over-dominant (CA vs. CC + AA) | 0.031 | 0.66 (0.46–0.96) |
Log-additive | 0.13 | 0.80 (0.61–1.07) | |||
HLA-DRB1*15:01-negative cohort | |||||
Allele contrast (A vs. C) | 0.52 | 1.07 (0.87–1.31) | |||
C | 382 (67.97%) | 1270 (69.40%) | Codominant (CA vs. CC) | 0.50 | 1.10 (0.82–1.47) |
A | 180 (32.03%) | 560 (30.60%) | Codominant (AA vs. CC) | 0.63 | 1.10 (0.69–1.77) |
CC | 131 (46.62%) | 439 (47.98%) | Dominant (AA + CA vs. CC) | 0.49 | 1.10 (0.84–1.45) |
CA | 120 (42.70%) | 392 (42.84%) | Recessive (AA vs. CA + CC) | 0.81 | 1.06 (0.67–1.66) |
AA | 30 (10.68%) | 84 (9.18%) | Over-dominant (CA vs. CC + AA) | 0.58 | 1.08 (0.82–1.43) |
Log-additive | 0.53 | 1.07 (0.87–1.31) |
CD33 rs3865444 A | HLA-DRB1*15:01 | MS (n = 579) | Controls (n = 1145) | Logistic Regression Analysis | SF (p-Value) | |
---|---|---|---|---|---|---|
p-Value | OR (95% CI) | |||||
− | − | 131 (22.63%) | 439 (38.34%) | reference | 0.62 (0.032) | |
+ | − | 150 (25.91%) | 476 (41.57%) | 0.49 | 1.10 (0.84–1.45) | |
− | + | 154 (26.60%) | 99 (8.65%) | <0.0001 | 5.39 (3.87–7.52) | |
+ | + | 144 (24.87%) | 131 (11.44%) | <0.0001 | 3.67 (2.68–5.03) |
A/G | RR-MS (n = 511) | SP-MS | GM | RR-MS vs. C | SP-MS vs. C | SP-MS vs. RR-MS | |||
---|---|---|---|---|---|---|---|---|---|
(n = 68) | p | OR (95% CI) | p | OR (95% CI) | p | OR (95% CI) | |||
AC | 0.64 | 1.04 (0.86–1.22) | 0.0032 | 0.52 (0.34–0.81) | 0.0023 | 0.50 (0.32–0.79) | |||
C | 696 (68.10%) | 110 (80.88%) | CD1 | 0.78 | 1.03 (0.81–1.32) | 0.0005 | 0.38 (0.21–0.67) | 0.0072 | 0.43 (0.23–0.81) |
A | 326 (31.90%) | 26 (19.12%) | CD2 | 0.52 | 1.13 (0.76–1.67) | 0.071 | 0.41 (0.14–1.18) | 0.040 | 0.33 (0.11–1.05) |
CC | 239 (46.77%) | 46 (67.65%) | D | 0.67 | 1.05 (0.84–1.32) | 0.0003 | 0.38 (0.22–0.65) | 0.0023 | 0.41 (0.23–0.74) |
CA | 218 (42.66%) | 18 (26.47%) | R | 0.59 | 1.11 (0.76–1.67) | 0.30 | 0.60 (0.21–1.71) | 0.15 | 0.46 (0.15–1.42) |
AA | 54 (10.57%) | 4 (5.88%) | OD | 0.92 | 1.01 (0.80–1.28) | 0.0016 | 0.42 (0.24–0.74) | 0.022 | 0.50 (0.27–0.92) |
LA | 0.57 | 1.05 (0.88–1.25) | 0.0007 | 0.48 (0.30–0.75) | 0.0028 | 0.50 (0.31–0.81) |
Phenotype | Patient Group | Genotypes | Best Model | p-Value | ||
---|---|---|---|---|---|---|
CC | CA | AA | ||||
Whole | 29.68 ± 9.66 | 29.62 ± 9.88 | 29.88 ± 10.09 | dominant | 0.88 * | |
AOO | HLA-DRB1*15:01 + | 28.60 ± 8.72 | 28.22 ± 9.22 | 30.54 ± 11.15 | recessive | 0.27 † |
HLA-DRB1*15:01 − | 30.96 ± 10.56 | 30.98 ± 10.34 | 29.27 ± 9.14 | recessive | 0.36 † | |
Whole | 4.43 ± 2.12 | 4.43 ± 2.10 | 4..27 ± 1.93 | recessive | 0.57 ‡ | |
MSSS | HLA-DRB1*15:01 + | 4.51 ± 1.99 | 4.45 ± 2.10 | 4.32 ± 1.95 | recessive | 0.41 $ |
HLA-DRB1*15:01 − | 4.34 ± 2.26 | 4.41 ± 2.11 | 4.23 ± 1.94 | dominant | 0.72 $ |
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Javor, J.; Bucová, M.; Ďurmanová, V.; Radošinská, D.; Párnická, Z.; Čierny, D.; Kurča, E.; Čopíková-Cudráková, D.; Gmitterová, K.; Shawkatová, I. Alzheimer’s Disease Risk Variant rs3865444 in the CD33 Gene: A Possible Role in Susceptibility to Multiple Sclerosis. Life 2022, 12, 1094. https://doi.org/10.3390/life12071094
Javor J, Bucová M, Ďurmanová V, Radošinská D, Párnická Z, Čierny D, Kurča E, Čopíková-Cudráková D, Gmitterová K, Shawkatová I. Alzheimer’s Disease Risk Variant rs3865444 in the CD33 Gene: A Possible Role in Susceptibility to Multiple Sclerosis. Life. 2022; 12(7):1094. https://doi.org/10.3390/life12071094
Chicago/Turabian StyleJavor, Juraj, Mária Bucová, Vladimíra Ďurmanová, Dominika Radošinská, Zuzana Párnická, Daniel Čierny, Egon Kurča, Daniela Čopíková-Cudráková, Karin Gmitterová, and Ivana Shawkatová. 2022. "Alzheimer’s Disease Risk Variant rs3865444 in the CD33 Gene: A Possible Role in Susceptibility to Multiple Sclerosis" Life 12, no. 7: 1094. https://doi.org/10.3390/life12071094