Association between PYTPN22 rs2476601, VEGF rs833070, TNFAIP3 rs6920220 Polymorphisms and Risk for Rheumatoid Arthritis in Early Undifferentiated Arthritis Patients: A Pilot Study
Abstract
:1. Introduction
2. Patients and Methods
2.1. Patients
2.2. Data and Sample Collection
2.3. Sample Preparation and SNP Genotyping
2.4. Statistical Analysis
3. Results
3.1. Patient Characteristics
3.2. SNP Analysis Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Variable | All UA Patients (n = 92) | RA Group (n = 27) | Non-RA Group (n = 65) | p Value * | Arthritis Resolved (n = 21) | p Value ** | Other Rheumatic Inflammatory Disease (n = 44) | p Value *** |
---|---|---|---|---|---|---|---|---|
Sociodemographics | ||||||||
Age, years | 44.25 ± 15.82 | 47.78 ± 16.36 | 42.79 ± 15.48 | 0.178 | 43.10 ± 15.67 | 0.266 | 42.34 ± 15.56 | 0.220 |
Females, n (%) | 61 (66.3) | 20 (74.1) | 41 (63.1) | 0.310 | 14 (66.7) | 0.575 | 27 (61.4) | 0.272 |
BMI, kg/m2 | 24.14 ± 3.43 | 23.71 ± 3.40 | 24.32 ± 3.18 | 0.318 | 23.74 ± 3.07 | 0.771 | 24.60 ± 3.22 | 0.225 |
Daily smokers, n (%) | 14 (15.2) | 4 (14.8) | 10 (15.4) | 0.945 | 5 (23.8) | 0.428 | 5 (11.4) | 0.671 |
Education, years | 13.40 ± 2.19 | 13.59 ± 1.95 | 13.32 ± 2.29 | 0.751 | 13.67 ± 2.4 | 0.865 | 13.16 ± 2.24 | 0.592 |
Presence of rheumatic disease in family, n (%) | 30 (32.6) | 12 (44.4) | 18 (27.7) | 0.119 | 7 (33.3) | 0.435 | 11 (25.0) | 0.671 |
Clinical data | ||||||||
Presence of active infection 1, n (%) | 23 (31.5) | 4 (14.8) | 25 (38.5) | 0.084 | 11 (52.4) | 0.014 | 14 (31.8) | 0.257 |
Presence of comorbidities, n (%) | 62 (67) | 21 (77.8) | 41 (63.1) | 0.171 | 13 (61.9) | 0.230 | 28 (63.6) | 0.211 |
Duration of joint pain, months | 6.74 ± 4.96 | 6.26 ± 4.68 | 6.94 ± 5.09 | 0.396 | 6.52 ± 3.53 | 0.497 | 7.14 ± 5.1 | 0.432 |
Duration of joint swelling, months | 5.27 ± 3.22 | 4.85 ± 3.21 | 5.45 ± 3.23 | 0.425 | 5.76 ± 2.91 | 0.233 | 5.92 ± 3.39 | 0.672 |
Duration of morning stiffness, minutes | 68.04 [0–300] | 92.78 [0–300] | 57.77 [0–300] | 0.117 | 52.86 [0–120] | 0.281 | 30 [0–300] | 0.122 |
Patient’s joint pain VAS, mm | 45.42 ± 16.99 | 43.89 ± 16.18 | 46.06 ± 17.39 | 0.431 | 45.29 ± 16.16 | 0.684 | 46.43 ± 18.12 | 0.391 |
Patient’s global VAS, mm | 47.98 ± 16.40 | 49.70 ± 18.04 | 47.26 ± 15.77 | 0.646 | 46.86 ± 17.13 | 0.446 | 47.46 ± 15.28 | 0.840 |
Physician’s global VAS, mm | 45.80 ± 13.89 | 46.07 ± 13.68 | 45.69 ± 14.08 | 0.931 | 44.67 ± 13.79 | 0.942 | 46.18 ± 14.35 | 0.938 |
66 SJC | 3.17 ± 2.14 [1–14] | 4.63 ± 2.80 [2–14] | 2.57 ± 1.44 [1–8] | <0.001 | 2.19 ± 0.87 | <0.001 | 2.75 ± 1.61 [1–8] | <0.001 |
28 SJC | 2.73 ± 1.6 [0–8] | 3.81 ± 1.71 [2–8] | 2.28 ± 1.24 [0–7] | <0.001 | 2.19 ± 1.21 | <0.001 | 2.32 ± 1.41 [0–7] | <0.001 |
68 TJC | 7.33 ± 5.77 [0–28] | 9.59 ± 6.03 [1–28] | 6.39 ± 5.43 [0–28] | 0.010 | 4.95 ± 4.23 | 0.003 | 7.07 ± 5.84 [0–28] | 0.060 |
28 TJC | 5.37 ± 3.75 [0–18] | 6.70 ± 3.75 [1–14] | 4.82 ± 3.63 [0–18] | 0.021 | 4.00 ± 3.22 | 0.015 | 5.20 ± 3.78 [0–18] | 0.071 |
HAQ | 0.63 ± 0.41 | 0.742 ± 0.47 | 0.58 ± 0.38 | 0.106 | 0.51 ± 0.32 | 0.052 | 0.61 ± 0.40 | 0.258 |
DAS 28 | 4.50 ± 1.09 | 5.01 ± 0.86 | 4.29 ± 1.11 | 0.005 | 4.67 ± 1.18 | 0.313 | 4.11 ± 1.05 | <0.001 |
Laboratory findings | ||||||||
ESR, mm/h | 32.55 [2–144] | 39.67 ± 34.51 | 29.45 ± 23.85 | 0.239 | 32.89 ±25.75 | 0.647 | 27.93 ± 23.11 | 0.178 |
CRP, mg/L | 17.65 [0.16–144.30] | 22.42 [0.39–111.50] | 15.67 [0.16–144.30] | 0.065 | 18.99 [0.30–84.90] | 0.430 | 4.6 [0.16–144.30] | 0.036 |
RF positive, n (%) | 31 (33.7) | 24 (88.9) (n = 27) | 7 (10.8) (n = 65) | <0.001 | 2 (9.5) (n = 21) | <0.0005 | 5 (11.4) (n = 44) | <0.001 |
Anti-CCP 2 positive, n (%) | 30 (36.1) | 24 (89.9) (n = 27) | 6 (10.7) (n = 56) | <0.001 | 1 (5.0) (n = 19) | <0.0005 | 5 (13.5) (n = 37) | <0.001 |
RF and anti-CCP positive, n (%) | 27 (31.0) | 22 (81.5) | 5 (8.9) | <0.001 | 1 (5.0) | <0.0005 | 4 (10.8) | <0.001 |
HLA B27 3 expressed, n (%) | 20 (28.2) | 1 (6.3) (n = 16) | 19 (34.5) (n = 55) | 0.010 | 3 (17.6) (n = 17) | 0.321 | 16 (42.1) (n = 38) | 0.010 |
ANA 4 positive, n (%) | 19 (45.2) | 5 (38.5) (n = 13) | 14 (48.3) (n = 29) | 0.238 | 1 (14.3) (n = 7) | 0.260 | 13 (59.1) (n = 22) | 0.555 |
VEGF 5, pg/mL | 516.16 [25.75–3438.25] | 697.60 [25.75–3438.25] (n = 23) | 437.42 [53.97–1854.91] (n = 53) | 0.086 | 449.50 [53.97–1437.35] (n = 20) | 0.242 | 283.42 [58.47–1854.91] (n = 33) | 0.083 |
Variable | All UA Patients (n = 92) | RA Group (n = 27) | Non-RA Group (n = 65) | p Value * | Arthritis Resolved (n = 21) | p Value ** | Other Rheumatic Inflammatory Disease (n = 44) | p Value *** |
---|---|---|---|---|---|---|---|---|
Synovitis score | 6.35 ± 4.58 | 9.78 ± 5.20 | 4.92 ± 3.44 | <0.001 | 3.81 ± 2.21 | <0.001 | 5.46 ± 3.81 | <0.001 |
Power Doppler score | 2.0 [0–14] | 6.0 [0–14] | 1.0 [0–10] | <0.001 | 1.0 [0–4] | <0.001 | 2.0 [0–10] | <0.001 |
Erosions (grade) median | 0.0 [0–10] | 2.0 [0–8] | 0.0 [0–10] | <0.001 | 0.0 [0,1] | <0.001 | 0.0 [0–10] | 0.004 |
Presence of erosions, n (%) | 34 (37.0) | 16 (59.3) | 18 (27.7) | 0.004 | 2 (9.5) | <0.001 | 16 (36.4) | 0.060 |
SNP | Chr | Position Base Pair | Minor Allele | MAF | N | Odds Ratio (OR) | p Value |
---|---|---|---|---|---|---|---|
rs2476601 | 1 | 113834946 | A | 0.1 | 92 | 0.99 | 0.98 |
rs833070 | 6 | 43774889 | G | 0.4 | 92 | 1.0 | 0.97 |
rs6920220 | 6 | 137685367 | A | 0.1 | 92 | 0.48 | 0.13 |
Single Nucleotide Polymorphisms | rs2476601 | rs833070 | rs6920220 | ||||
---|---|---|---|---|---|---|---|
Variable | p Value | p Value | p Value | ||||
Patients’ distribution based on genotype | AA + AG/GG 23/69 | - | GG + GA/AA 16/76 | - | AA + AG/GG 30/62 | - | |
66 SJC | 2.96 ± 1.88; 2 [1–8] * | 0.619 | 3.00 ± 1.90; 3 [1–8] * | 0.485 | 3.1 ± 2.68; 2 [1–14] * | 0.171 | |
3.27 ± 2.26; 3 [1–14] * | 3.25 ± 2.24; 2 [1–14] * | 3.21 ± 1.84; 3 [1–12] * | |||||
28 SJC | 2.46 ± 1.32; 2 [1–5] * | 0.718 | 2.48 ± 1.34; 2 [1–5] * | 0.385 | 2.53 ± 1.59; 2 [1–8] * | 0.262 | |
2.84 ± 1.72; 2 [0–8] * | 2.83 ± 1.71; 2 [0–8] * | 2.82 ± 1.62; 2 [0–8] * | |||||
68 TJC | 6.61 ± 4.62; 6 [1–17] * | 0.368 | 6.78 ± 4.62; 6 [1–17] * | 0.901 | 5.87 ± 6.25; 4 [1–28] * | 0.019 | |
7.64 ± 6.21; 6 [0–28] * | 7.55 ± 6.21; 6 [0–28] * | 8.03 ± 5.44; 7 [0–24] * | |||||
28 TJC | 4.96 ± 3.05; 4 [1–14] * | 0.654 | 5.07 ± 3.05; 5 [1–14] * | 0.836 | 4.37 ± 3.84; 3 [0–18] * | 0.025 | |
5.54 ± 4.02; 4 [0–18] * | 5.49 ± 4.02; 4 [0–18] * | 5.85 ± 3.63; 5 [0–14] * | |||||
ESR, mm/h | 29 [2–144] | 0.754 | 27.0 [2–144] | 0.590 | 22.0 [2–110] | 0.853 | |
17 [2–88] | 19.50 [2–88] | 27.0 [2–144] | |||||
CRP, mg/L | 5.03 [0.20–111.50] | 0.732 | 6.47 [0.20–111.50] | 0.646 | 4.3 [0.16–111.50] | 0.500 | |
4.48 [0.16–144.30] | 4.35 [0.16–144.30] | 7.32 [0.20–144.30] | |||||
RF, kU/L | 20.0 [20.00–814.20] | 0.637 | 20.0 [20.00–814.20] | 0.417 | 20 [9.59–814.20] | 0.674 | |
20.0 [9.59–306.00] | 20.0 [9.59–306.00] | 20 [20.00–240.30] | |||||
RF positive (>30 kU/L) | 11 (39.3) | 0.702 | 11 (40.7) | 0.357 | 9 (30.0) | 0.602 | |
20 (31.3) | 20 (30.8) | 22 (35.5) | |||||
Anti-CCP, U/L | 2.0 [2–300] | 0.136 | 2.0 [2–300] | 0.387 | 2.0 [2–300] | 0.871 | |
2.0 [2–300] | 2.0 [2–300] | 2.0 [2–300] | |||||
Anti-CCP positive (≥5 U/mL) | 11 (44.0) | 0.134 | 10 (41.7) | 0.384 | 10 (33.3) | 0.870 | |
19 (30.6) | 20 (31.7) | 20 (35.1) | |||||
RF and anti-CCP positive | 10 (40.0) | 0.991 | 10 (41.7) | 0.186 | 9 (30.0) | 0.880 | |
17 (27.4) | 17 (27.0) | 18 (31.6) | |||||
HLA B27 expressed | 6 (28.6) | 0.516 | 6 (30.0) | 0.830 | 5 (23.8) | 0.597 | |
14 (28.0) | 14 (27.5) | 15 (30.0) | |||||
ANA positive | 7 (46.7) | 0.327 | 6 (42.9) | 0.826 | 4 (26.7) | 0.071 | |
12 (44.4) | 13 (46.4) | 15 (55.6) | |||||
VEGF, pg/mL | 384.64 [25.75–3438.23] | 0.563 | 374.37 [68.67–3438.23] | 0.773 | 284.91 [115.88–3438.23] | 0.323 | |
312.46 [68.67–1854.91] | 272.30 [25.75–1854.91] | 414.47 [25.75–1967.50] | |||||
Synovitis, scores | 6.29 ± 4.22; 5 [2–16] * | 0.806 | 6.37 ± 4.28; 5 [2–16] * | 0.938 | 5.87 ± 5.31; 4 [2–25] * | 0.215 | |
6.37 ± 4.77; 5 [2–25] * | 6.34 ± 4.74; 4 [2–25] * | 6.5 ± 4.22; 5 [2–21] * | |||||
PD, scores | 2.79 ± 2.84; 2 [0–10] * | 0.627 | 2.89 ± 2.85; 2 [0–10] * | 0.798 | 2.70 ± 3.26; 2 [0–12] * | 0.164 | |
3.17 ± 3.13; 3 [0–14] * | 3.12 ± 3.14; 2 [0–14] * | 3.23 ± 2.94; 3 [0–14] * | |||||
Erosions, scores | 1.18 ± 1.89; 0 [0–6] * | 0.722 | 1.22 ± 1.91; 0 [0–6] * | 0.988 | 1.03 ± 1.90; 0 [0–8] * | 0.468 | |
1.31 ± 2.23; 0 [0–10] * | 1.29 ± 2.22; 0 [0–10] * | 1.39 ± 2.23; 0 [0–10] * | |||||
Erosions detected | 9 (32.1) | 0.803 | 9 (33.3) | 0.643 | 9 (30.0) | 0.336 | |
25 (39.1) | 25 (38.5) | 25 (40.3) |
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Sakalyte, R.; Stropuviene, S.; Jasionyte, G.; Bagdonaite, L.; Venalis, A. Association between PYTPN22 rs2476601, VEGF rs833070, TNFAIP3 rs6920220 Polymorphisms and Risk for Rheumatoid Arthritis in Early Undifferentiated Arthritis Patients: A Pilot Study. Medicina 2023, 59, 1824. https://doi.org/10.3390/medicina59101824
Sakalyte R, Stropuviene S, Jasionyte G, Bagdonaite L, Venalis A. Association between PYTPN22 rs2476601, VEGF rs833070, TNFAIP3 rs6920220 Polymorphisms and Risk for Rheumatoid Arthritis in Early Undifferentiated Arthritis Patients: A Pilot Study. Medicina. 2023; 59(10):1824. https://doi.org/10.3390/medicina59101824
Chicago/Turabian StyleSakalyte, Regina, Sigita Stropuviene, Gabija Jasionyte, Loreta Bagdonaite, and Algirdas Venalis. 2023. "Association between PYTPN22 rs2476601, VEGF rs833070, TNFAIP3 rs6920220 Polymorphisms and Risk for Rheumatoid Arthritis in Early Undifferentiated Arthritis Patients: A Pilot Study" Medicina 59, no. 10: 1824. https://doi.org/10.3390/medicina59101824