Association of the Gelatinase B/Metalloproteinase 9 (MMP-9) Gene Haplotype in Systemic Lupus Erythematosus (SLE) in the Pediatric Egyptian Population
Abstract
:1. Introduction
2. Materials and Methods
2.1. Participants in the Study
2.2. Collection and Processing of Samples
2.3. Genetic Testing and DNA Extraction
2.4. Statistical Methods
- Dominant: “AA + AB” versus “BB”
- Additive: “AA” versus “AB” versus “BB”
- Allelic: A versus B
3. Results
3.1. The Study Population’s Clinical Manifestations
3.2. Gelatinase B/MMP-9 Determination in Serum
3.3. Association of Gelatinase B/MMP-9 rs3918249 T/C and rs17576 A/G Genotypes, Alleles, or Haplotypes with SLE Risk
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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SLE Patients | Healthy Control | |
---|---|---|
Number | 100 | 100 |
Sex ratio (female/male) (%) | 94/6 | 93/7 |
Age (y) (mean ± SD) | (13.8 ± 2.9) | (13.5 ± 1.9) |
Duration of the disease (y) (mean ± SD) | (3.6 ± 2.9) | n. a. |
SLEDAI median (minimum–maximum) | 8 (0–19) | n. a. |
Active (SLEDAI > 10) (%) | 49 | n. a. |
Inactive (SLEDAI < 10) (%) | 51 | |
Clinical features | ||
Serositis (pleurisy/pericarditis) (%) | 3 | n. a. |
Oropharyngeal ulcers (%) | 10 | n. a. |
Neurologic disorders (%) | 13 | n. a. |
Non-scarring alopecia (%) | 31 | n. a. |
Arthritis (%) | 27 | n. a. |
Photosensitivity (%) | 32 | n. a. |
Malar rash (%) | 39 | n. a. |
Laboratory findings | ||
complement components (C3/C4) (%) | 97 | n. a. |
Anti-ds-DNA antibodies (%) | 68 | n. a. |
Antinuclear antibody (%) | 92 | n. a. |
Hemolytic Anemia (%) | 64 | n. a. |
Thrombocytopenia (%) | 12 | n. a. |
Leucopenia/lymphopenia (%) | 10 | n. a. |
Pancytopenia (%) | 5 | n. a. |
Persistent proteinuria (%) | 72 | n. a. |
RBCs casts (%) | 23 | n. a. |
Studied Parameters | Control (n = 100) | SLE (n = 100) | p Values |
---|---|---|---|
White blood cells (×109/L) (M± SD) | (8.7 ± 1.5) | (6.6 ± 1.6) | 0.003 |
Red blood cells (×106/L) (M ± SD) | (4.9 ± 0.4) | (4.5 ± 0.6) | 0.032 |
Hemoglobin (g/dL) (M ± SD) | (12.9 ± 1.8) | (11.7 ± 2.8) | 0.004 |
Platelets (×109/L) (M ± SD) | (394.3 ± 66.2) | (282.1 ± 91.4) | <0.001 |
Creatinine (mg/dL) (M ± SD) | (0.7 ± 0.1) | (0.7 ± 0.2) | 0.231 |
Phosphorus (mg/dL) (M ± SD) | (4.8 ± 0.5) | (4.9 ± 0.7) | 0.272 |
Calcium (mg/dL) (M ± SD) | (9.2 ± 0.4) | (9.4 ± 0.7) | 0.462 |
Complement 3 (mg/dL) (M ± SD) | (121.3 ± 18.1) | (107.9 ± 35.4) | 0.001 |
Complement 4 (mg/dL) (M ± SD) | (22.4 ± 6.8) | 14.1 | <0.001 |
Positive ANA (n, %) | n. a. | 92 (92%) | n. a. |
Positive Anti ds-DNA (n, %) | n. a. | 68 (68%) | n. a. |
Serum MMP-9 (×102 ng/L) [med (min–max)] | 22 (10.4–30) | 8 (1.1–37) | <0.001 |
Genetic Model | Genotype | Controls | SLE | p | OR | 95% CI |
---|---|---|---|---|---|---|
(n = 100) | (n = 100) | |||||
MMP-9 rs3918249 T/C | ||||||
Additive model | TT, n (%) | 19(19%) | 16(16%) | - | 1 | Reference |
TC, n (%) | 40 (40%) | 42 (42%) | 0.586 | 1.148 | 0.699–1.887 | |
CC, n (%) | 41 (41%) | 42 (42%) | 0.628 | 1.131 | 0.689–1.856 | |
Dominant model | TC + TT, n (%) | 81 (81%) | 84 (84%) | 0.577 | 1.139 | 0.721–1.801 |
Allelic model | T, n (%) | 78 (39%) | 74 (37%) | - | 1 | Reference |
C, n (%) | 122 (61%) | 126 (63%) | 0.680 | 1.055 | 0.819–1.358 | |
HWE | 0.111 | 0.322 | ||||
MMP-9 rs17576 A/G | ||||||
Additive model | AA, n (%) | 46(46%) | 55(55%) | - | 1 | Reference |
AG, n (%) | 37(37%) | 33(33%) | 0.347 | 0.832 | 0.568–1.220 | |
GG, n (%) | 17(17%) | 12(12%) | 0.215 | 0.719 | 0.427–1.211 | |
Dominant model | AG + GG, n (%) | 54(54%) | 45(45%) | 0.203 | 0.798 | 0.563–1.130 |
Allelic model | A, n (%) | 129(64.5%) | 143(71.5%) | - | 1 | Reference |
G, n (%) | 71(35.5%) | 75(28.5%) | 0.134 | 0.817 | 0.627–1.064 | |
HWE | 0.055 | 0.057 |
Haplotype | rs3918249 T/C | rs17576 A/G | Controls (Frequency) | SLE Patients (Frequency) | p | OR | 95% CI |
---|---|---|---|---|---|---|---|
1 | T | A | 0.059 | 0.254 | - | 1 | - |
2 | C | A | 0.586 | 0.461 | <0.001 | 0.36 | 0.206–0.631 |
3 | T | G | 0.331 | 0.116 | <0.001 | 0.226 | 0.119–0.429 |
4 | C | G | 0.024 | 0.169 | 0.405 | 1.473 | 0.592–3.664 |
Clinical SLE Features | n (%) | Gelatinase B/MMP-9 (rs3918249 T/C) | p Values | Gelatinase B/MMP-9 (rs17576 A/G) | p Values | ||||
---|---|---|---|---|---|---|---|---|---|
TT (n = 16) | TC (n = 42) | CC (n = 42) | AA (n = 55) | AG (n = 33) | GG (n = 12) | ||||
Skin | 53 (53%) | 9 (56.3%) | 24 (57.1%) | 20 (47.6%) | 0.776 | 26 (47.3%) | 17 (51.5%) | 10 (83.3%) | 0.205 |
Ulcers | 10 (10%) | 2 (12.5%) | 3 (7.1%) | 5 (11.9%) | 0.721 | 3 (5.5%) | 5 (12.2%) | 2 (16.7%) | 0.099 |
Alopecia | 31 (31%) | 2 (12.5%) | 17 (40.5%) | 12 (28.6%) | 0.077 | 17 (30.9%) | 10 (30.3%) | 4 (33.3%) | 0.983 |
Arthritis | 27 (27%) | 1 (6.3%) | 12 (28.6%) | 14 (33.3%) | 0.088 | 12 (21.8%) | 11 (33.3%) | 4 (33.3%) | 0.198 |
Serositis | 3 (3%) | 0 (0%) | 1 (2.4%) | 2 (4.8%) | 0.999 | 1 (1.8%) | 1 (3%) | 1 (8.3%) | 0.451 |
Neurologic | 13 (13%) | 0 (0%) | 10 (23.8%) | 3 (7.1%) | 0.999 | 8 (14.5%) | 3 (9.1%) | 2 (16.7%) | 0.611 |
Blood disorder | 72 (72%) | 11 (68.8%) | 31 (73.8%) | 30(71.4%) | 0.754 | 41 (74.5%) | 21 (63.6%) | 10 (83.3%) | 0.531 |
Nephritis | 67 (67%) | 8 (50%) | 27 (64.3%) | 32 (76.2%) | 0.123 | 36 (65.5%) | 22 (66.7%) | 9 (75%) | 0.716 |
SLEDAI %, [med (min–max)] | 100 (100%) | 8 (0–19) | 9 (4–19) | 10 (0–18) | 0.452 | 8 (0–19) | 8 (4–19) | 10 (8–18) | 0.705 |
Active SLE > 10 | 49(49%) | 10 (62.5%) | 21 (50.0%) | 20 (47.6%) | 0.316 | 29 (52.7%) | 18 (54.5%) | 4 (33.3%) | 0.702 |
Inactive SLE < 10 | 51 (51%) | 6 (37.5%) | 21 (50.0%) | 22 (52.4%) | 26 (47.3%) | 15 (45.5%) | 8 (66.7%) | ||
S.MMP-9 %, [med (min–max)] | 100 (100%) | 10 (3.1–22) | 7.5 (2.3–22.8) | 8.35 (1.1–37) | 0.721 | 8.6 (2.3–22.8) | 9.2 (2–37) | 5.6 (1.1–22) | 0.792 |
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Attia, Z.R.; Zedan, M.M.; Mutawi, T.M.; Saad, E.A.; Abd El Azeem, R.A.; El Basuni, M.A. Association of the Gelatinase B/Metalloproteinase 9 (MMP-9) Gene Haplotype in Systemic Lupus Erythematosus (SLE) in the Pediatric Egyptian Population. Children 2022, 9, 1271. https://doi.org/10.3390/children9091271
Attia ZR, Zedan MM, Mutawi TM, Saad EA, Abd El Azeem RA, El Basuni MA. Association of the Gelatinase B/Metalloproteinase 9 (MMP-9) Gene Haplotype in Systemic Lupus Erythematosus (SLE) in the Pediatric Egyptian Population. Children. 2022; 9(9):1271. https://doi.org/10.3390/children9091271
Chicago/Turabian StyleAttia, Zeinab R., Mohamed M. Zedan, Thuraya M. Mutawi, Entsar A. Saad, Rania A. Abd El Azeem, and Mohamed A. El Basuni. 2022. "Association of the Gelatinase B/Metalloproteinase 9 (MMP-9) Gene Haplotype in Systemic Lupus Erythematosus (SLE) in the Pediatric Egyptian Population" Children 9, no. 9: 1271. https://doi.org/10.3390/children9091271
APA StyleAttia, Z. R., Zedan, M. M., Mutawi, T. M., Saad, E. A., Abd El Azeem, R. A., & El Basuni, M. A. (2022). Association of the Gelatinase B/Metalloproteinase 9 (MMP-9) Gene Haplotype in Systemic Lupus Erythematosus (SLE) in the Pediatric Egyptian Population. Children, 9(9), 1271. https://doi.org/10.3390/children9091271