SNP in PTPN22, PADI4, and STAT4 but Not TRAF1 and CD40 Increase the Risk of Rheumatoid Arthritis in Polish Population
Abstract
:1. Introduction
2. Results
2.1. Characteristics of the Study Population
2.2. The Hardy–Weinberg Equilibrium Analysis
2.3. Analysis of a Relationship between the Occurrence of RA and the Studied Polymorphic Variants of PTPN22, PADI4, TRAF1, STAT4, and CD40 Genes
2.4. Haplotype Analysis
2.5. Sample Power
3. Discussion
4. Materials and Methods
4.1. Patients and Control Group
4.2. Genotyping
4.3. Data Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Parameters | RA Patients n = 181 | Control Group n = 153 |
---|---|---|
Sex | F-145 M-36 | F-117 M-36 |
Age | 61 ± 13 years | 45 ± 16 |
Disease duration | 19 ± 10 years | |
Remission | yes 14; no 167 | |
CRP | 16.3 ± 17.1 | |
ESR | 23.9 ± 22.5 | |
RF | 158.2 ± 211.6 | |
ACPA | 589.1 ± 303.1 | |
Treatment | Methotrexate 132/181 Sulfasalazine 11/181 Leflunomide 13/50 Chloroquine 3/50 No DMARDs 37/50 Glucocorticosteroids 82/181 |
Gene Polymorphism | p-Value | ||
---|---|---|---|
All Subjects | Control Group | Study Group | |
PTPN22.rs2476601 | 0.67 | 1 | 0.81 |
PADI4.rs2240340 | p < 0.05 | p < 0.05 | 1 |
TRAF1.rs3761847 | 0.34 | 0.61 | 0.41 |
STAT4.rs7574865 | 1 | 1 | 0.69 |
CD40.rs4810485 | 0.86 | 0.66 | 0.25 |
Gene SNP | Chr * | Positions ** | Allele | Minor Allele Frequency | |
---|---|---|---|---|---|
Case | Control | ||||
PTPN22.rs2476601 | 1 | 113834946 | A/G | 0.19 | 0.11 |
PADI4.rs2240340 | 1 | 17336144 | C/T | 0.44 | 0.27 |
TRAF1.rs3761847 | 9 | 120927961 | A/G | 0.45 | 0.41 |
STAT4.rs7574865 | 2 | 191099907 | G/T | 0.28 | 0.16 |
CD40.rs4810485 | 20 | 46119308 | G/T | 0.18 | 0.24 |
Gene Polymorphism | Genotype | Control Group | RA Group | OR (95% CI) | p-Value |
---|---|---|---|---|---|
PTPN22.rs2476601 | G/G | 119 (79%) | 92 (61%) | 1.00 | p < 0.00001 |
G/A | 30 (20%) | 50 (33%) | 2.16 (1.27–3.66) | ||
A/A | 1 (1%) | 8 (5%) | 10.35 (1.27–84.21) | ||
G | 268 (89%) | 235 (78%) | 0.43 (0.27–0.68) | p = 0.0003 | |
A | 32 (11%) | 65 (22%) | 2.32 (1.47–3.66) | ||
PADI4.rs2240340 | C/C | 96 (64%) | 48 (32%) | 1.00 | p < 0.0001 |
C/T | 34 (23%) | 74 (49%) | 4.35 (2.55–7.42) | ||
T/T | 20 (13%) | 28 (19%) | 2.80 (1.43–4.10) | ||
C | 226 (75%) | 170 (57%) | 0.42 (0.3–0.6) | p < 0.0001 | |
T | 74 (25%) | 130 (43%) | 2.335 (1.64–3.31) | ||
TRAF1.rs3761847 | A/A | 54 (36%) | 42 (28%) | 1.00 | 0.26 |
A/G | 75 (50%) | 80 (53%) | 1.37 (0.82–2.29) | ||
G/G | 21 (14%) | 28 (19%) | 1.71 (0.86–3.43) | ||
A | 183 (61%) | 164 (55%) | 0.77 (0.56–1.07) | p = 0.1165 | |
G | 117 (39%) | 136 (45%) | 1.29 (0.93–1.79) | ||
STAT4.rs7574865 | G/G | 104 (69%) | 78 (52%) | 1.00 | 0.0059 |
G/T | 42 (28%) | 62 (41%) | 1.97 (1.21–3.21) | ||
T/T | 4 (3%) | 10 (7%) | 3.33 (1.01–11.02) | ||
G | 250 (83%) | 218 (73%) | 0.53 (0.36–0.79) | p = 0.0018 | |
T | 50 (17%) | 82 (17%) | 1.88 (1.27–2.79) | ||
CD40.rs4810485 | G/G | 86 (6%) | 100 (1%) | 1.00 | 0.027 * |
G/T | 54 (37%) | 48 (34%) | 0.76 (0.47–1.24) | ||
T/T | 10 (57%) | 2 (65%) | 0.17 (0.04–0.81) * | ||
G | 226 (75%) | 248 (83%) | 1.56 (1.05–2.33) * | p = 0.02 * | |
T | 74 (25%) | 52 (17%) | 0.64 (0.43–0.95) * |
Gene Polymorphism | PADI4 rs2240340 | STAT4 rs7574865 | PTPN22 rs2476601 | TRAF1 rs3761847 | CD40 rs4810485 |
---|---|---|---|---|---|
PADI4 rs2240340 | *** | 0.1872 | 0.1236 | 0.1447 | 0.0031 |
STAT4 rs7574865 | *** | *** | 0.1561 | 0.0894 | 0.0494 |
PTPN22 rs2476601 | *** | *** | *** | 0.1296 | 0.0485 |
TRAF1 rs3761847 | *** | *** | *** | *** | 0.1091 |
CD40 rs4810485 | *** | *** | *** | *** | *** |
Number | PADI4 rs2240340 | STAT4 rs7574865 | PTPN22 rs2476601 | TRAF1 rs3761847 | CD40 rs4810485 | Total |
---|---|---|---|---|---|---|
1 | C | G | G | A | G | 0.2405 |
2 | C | G | G | G | G | 0.1312 |
3 | T | G | G | G | G | 0.0816 |
4 | T | G | G | A | G | 0.0808 |
5 | C | G | G | A | T | 0.0596 |
6 | C | G | G | G | T | 0.0448 |
7 | C | T | G | A | G | 0.0421 |
8 | T | T | G | A | G | 0.0407 |
9 | C | G | A | A | G | 0.0359 |
10 | C | T | G | G | G | 0.0275 |
11 | T | T | G | G | G | 0.0223 |
12 | T | G | G | A | T | 0.0203 |
Rare | * | * | * | * | * | 0.1728 |
Number | PADI4 rs2240340 | STAT4 rs7574865 | PTPN22 rs2476601 | TRAF1 rs3761847 | CD40 rs4810485 | OR (95% CI) | p-Value |
---|---|---|---|---|---|---|---|
1 | C | G | G | A | G | 1 | --- |
2 | C | G | G | G | G | 0.53 (0.24–1.18) | 0.12 |
3 | T | G | G | G | G | 3.27 (1.23–8.72) # | 0.019 # |
4 | T | G | G | A | G | 0.47 (0.18–1.26) | 0.13 |
5 | C | G | G | A | T | 0.42 (0.13–1.36) | 0.15 |
6 | C | G | G | G | T | 12.28 (2.65–56.91) | 0.0015 |
7 | C | T | G | A | G | 0.28 (0.07–1.19) | 0.086 |
8 | T | T | G | A | G | 1.07 (0.29–3.92) | 0.92 |
9 | C | G | A | A | G | 0.33 (0.06–1.72) | 0.19 |
10 | C | T | G | G | G | 0.16 (0.02–1.18) | 0.072 |
11 | T | T | G | G | G | 0.05 (0.00–0.61) # | 0.02 # |
12 | T | G | G | A | T | 0.38 (0.02–6.87) | 0.51 |
Rare | * | * | * | * | * | 3.23 (1.63–6.39) | 0.0009 |
Gene | RS Number 1 | Assay ID 2 |
---|---|---|
PTPN22 | rs2476601 | C__16021387_20 |
PADI4 | rs2240340 | C__16176717_10 |
TRAF1 | rs3761847 | C___2783640_10 |
STAT4 | rs7574865 | C__29882391_10 |
CD40 | rs4810485 | C___1260190_10 |
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Budlewski, T.; Sarnik, J.; Galita, G.; Dragan, G.; Brzezińska, O.; Popławska, M.; Popławski, T.; Makowska, J. SNP in PTPN22, PADI4, and STAT4 but Not TRAF1 and CD40 Increase the Risk of Rheumatoid Arthritis in Polish Population. Int. J. Mol. Sci. 2023, 24, 7586. https://doi.org/10.3390/ijms24087586
Budlewski T, Sarnik J, Galita G, Dragan G, Brzezińska O, Popławska M, Popławski T, Makowska J. SNP in PTPN22, PADI4, and STAT4 but Not TRAF1 and CD40 Increase the Risk of Rheumatoid Arthritis in Polish Population. International Journal of Molecular Sciences. 2023; 24(8):7586. https://doi.org/10.3390/ijms24087586
Chicago/Turabian StyleBudlewski, Tomasz, Joanna Sarnik, Grzegorz Galita, Grzegorz Dragan, Olga Brzezińska, Marta Popławska, Tomasz Popławski, and Joanna Makowska. 2023. "SNP in PTPN22, PADI4, and STAT4 but Not TRAF1 and CD40 Increase the Risk of Rheumatoid Arthritis in Polish Population" International Journal of Molecular Sciences 24, no. 8: 7586. https://doi.org/10.3390/ijms24087586