Interleukin Gene Variability and Periodontal Bacteria in Patients with Generalized Aggressive Form of Periodontitis
Abstract
:1. Introduction
2. Results
2.1. Genetic Analysis
2.2. Determination of the Selected Oral Bacteria
2.3. A Pilot In Vitro Study: IL-10 Levels in Unstimulated/Stimulated PBMCs
3. Discussion
3.1. Interleukin-1 Family
3.2. Interleukin-6
3.3. Interleukin-17
3.4. Interleukin-10
3.5. A Pilot In Vitro Study
4. Materials and Methods
4.1. Study Design, Clinical Examination and Sample Collection
4.2. Isolation of Genomic DNA and Genetic Analysis
4.3. Microbial Analysis
4.4. PBMCs Isolation, Cultivation and Stimulation by Oral Bacteria In Vitro
4.5. Determination of Interleukin-10 Levels in PBMCs
4.6. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
AgP | Aggressive periodontitis |
AS-PCR | Allele-specific polymerase chain reaction |
cAMP | Cyclic adenosine monophosphate |
CFU | Colony-forming units |
CI | Confidence interval |
CP | Chronic periodontitis |
CPITN | Community Periodontal Index of Treatment Needs |
dNTPs | Deoxyribonucleoside triphosphate mix |
EDTA | Ethylenediaminetetraacetic acid |
HWE | Hardy–Weinberg equilibrium |
IL | Interleukin |
IQR | Interquartile range |
LD | Linkage disequilibrium |
LPS | Lipopolysaccharides |
MAF | Minor allele frequencies |
MHC | Histocompatibility complex |
N | Number of individuals |
NF-1 | Nuclear factor 1 |
NFAT | Nuclear factor activated T cells |
NFκB | Nuclear factor kappa B |
OR | Odds ratio |
PAMP | Pathogen-associated molecular patterns |
PARP-1 | Poly (ADP-ribose) polymerase-1 |
PBMCs | Peripheral blood monocytes |
PCR | Polymerase chain reaction |
PWM | Pokeweed mitogen |
RFLP-PCR | Restriction fragment length polymorphism PCR |
SD | Standard deviation |
SNP | Single-nucleotide polymorphism |
Th1/2 | T helper 1/2 |
TLR4 | Toll-like receptor 4 |
TNF-α | Tumor necrosis factor-alpha |
VNTR | Variable tandem repeats |
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Polymorphism | Genotype MAF | Patients with AgP N = 91 (%) | Controls N = 210 (%) | p | OR 95% CI |
---|---|---|---|---|---|
IL-1A −889 C/T (rs1800587) | CC | 46 (50.5) | 95 (45.2) | 1.00 | |
CT | 32 (35.2) | 97 (46.2) | 0.68 (0.40–1.16) | ||
TT | 13 (14.3) | 18 (8.6) | 0.12 | 1.49 (0.67–3.30) | |
T | (31.9) | (31.7) | 0.52 | 1.01 (0.69–1.47) | |
IL-1B +3953 C/T (rs1143634) | CC | 51 (56.0) | 111 (52.9) | 1.00 | |
CT | 33 (36.3) | 83 (39.5) | 0.87 (0.51–1.46) | ||
TT | 7 (7.7) | 16 (7.6) | 0.86 | 1.05 (0.41–2.71) | |
T | (25.8) | (27.4) | 0.39 | 0.92 (0.62–1.37) | |
IL-1 VNTR§ intron 2, 86 bp VNTR (rs2234663) | LL | 51 (56.0) | 114 (54.3) | 1.00 | |
LS | 33 (36.3) | 79 (37.6) | 0.93 (0.55–1.58) | ||
SS | 7 (7.7) | 17 (8.1) | 0.96 | 0.92 (0.36–2.36) | |
S | (25.8) | (26.9) | 0.43 | 0.95 (0.64–1.41) | |
IL-6 −174 C/G (rs1800795) | GG | 27 (29.6) | 69 (32.9) | 1.00 | |
GC | 41 (45.1) | 101 (48.1) | 0.96 (0.54–1.71) | ||
CC | 23 (25.3) | 40 (19.0) | 0.47 | 1.47 (0.75–2.90) | |
C | (47.8) | (43.1) | 0.16 | 0.83 (0.58–1.17) | |
IL-6R +48992 A/C (rs2228145) | AA | 32 (35.2) | 76 (36.2) | 1.00 | |
AC | 46 (50.5) | 101 (48.1) | 1.08 (0.63–1.86) | ||
CC | 13 (14.3) | 33 (15.7) | 0.91 | 0.94 (0.44–2.01) | |
C | (39.6) | (39.8) | 0.52 | 0.99 (0.69–1.42) | |
IL-10 −1087 A/G (rs1800896) | AA | 23 (25.3) | 54 (25.7) | 1.00 | |
AG | 44 (48.4) | 124 (59.1) | 0.83 (0.46–1.51) | ||
GG | 24 (26.4) | 32 (15.2) | 0.06 | 1.76 (0.86–3.62) | |
AG + AA | 67 (73.6) | 178 (84.8) | 0.02 * | 0.50 (0.28–0.91) | |
G | (50.5) | (44.8) | 0.12 | 1.26 (0.89–1.79) | |
IL-10 −824 C/T (rs1800871) | CC | 49 (53.8) | 118 (56.2) | 1.00 | |
CT | 39 (42.9) | 82 (39.0) | 1.15 (0.69–1.90) | ||
TT | 3 (3.3) | 10 (4.8) | 0.74 | 0.72 (0.19–2.74) | |
T | (24.7) | (24.3) | 0.49 | 1.02 (0.68–1.53) | |
IL-10 −597 C/A (rs1800872) | CC | 50 (54.9) | 122 (58.1) | 1.00 | |
CA | 38 (41.8) | 78 (37.1) | 1.19 (0.71–1.98) | ||
AA | 3 (3.3) | 10 (4.8) | 0.68 | 0.73 (0.19–2.77) | |
A | (24.2) | (23.3) | 0.45 | 1.05 (0.70–1.58) | |
IL-17A −197 A/G (rs2275913) | GG | 46 (50.5) | 92 (43.8) | 1.00 | |
GA | 34 (37.4) | 92 (43.8) | 0.74 (0.44–1.25) | ||
AA | 11 (12.1) | 26 (12.4) | 0.53 | 0.85 (0.38–1.86) | |
A | (30.8) | (34.4) | 0.23 | 1.17 (0.81–1.71) | |
IL-18 −607 A/C (rs1946518) | CC | 25 (27.5) | 71 (34.0) | 1.00 | |
AC | 54 (59.3) | 109 (52.2) | 1.41 (0.80–2.46) | ||
AA | 12 (13.2) | 29 (13.8) | 0.48 | 0.85 (0.38–1.92) | |
A | (42.9) | (39.8) | 0.28 | 1.13 (0.79–1.60) | |
IL-18 −137 C/G (rs187238) | GG | 45 (49.4) | 97 (46.4) | 1.00 | |
GC | 42 (46.2) | 93 (44.5) | 1.03 (0.62–1.71) | ||
CC | 4 (4.4) | 19 (9.1) | 0.45 (0.15–1.41) | ||
C | (27.5) | (31.7) | 0.20 | 1.21 (0.82–1.77) | |
IL-18 −140 C/G (rs4988359) | CC | 39(42.9) | 85 (40.7) # | 1.00 | |
GC | 45 (49.4) | 97 (46.4) | 1.01 (0.60–1.70) | ||
GG | 7 (7.7) | 25 (12.0) | 0.52 | 0.61 (0.24–1.53) | |
G | (32.4) | (36.4) | 0.26 | 1.15 (0.79–1.66) |
Gene | Haplotype ‡ | Patients with AgP N = 91 (%) | Controls N = 210 (%) | p | OR 95% CI | ||
---|---|---|---|---|---|---|---|
IL-1 | C | C | A | (45.2) | (42.8) | 0.54 | 1.12 (0.79–1.59) |
T | T | A | (20.5) | (21.9) | 0.65 | 0.91 (0.60–1.38) | |
C | C | B | (20.0) | (21.6) | 0.58 | 0.89 (0.59–1.35) | |
T | C | A | (7.0) | (5.5) | 0.58 | 1.21 (0.62–2.37) | |
C | T | A | (1.4) | (2.9) | 0.36 | 0.57 (0.16–2.04) | |
T | C | B | (2.0) | (2.7) | 0.74 | 0.77 (0.15–3.84) | |
T | T | B | (2.4) | (1.6) | 0.31 | 2.33 (0.47–11.65) | |
C | T | B | (1.5) | (1.0) | 0.64 | 1.54 (0.26–9.32) | |
IL-10 | G | C | C | (50.5) | (44.4) | 0.17 | 1.27 (0.90–1.81) |
A | C | C | (24.2) | (31.1) | 0.09 | 0.71 (0.48–1.06) | |
A | T | A | (23.6) | (22.7) | 0.84 | 0.69 (0.57–1.58) | |
A | T | C | (1.1) | (1.2) | 0.92 | 0.92 (0.18–4.80) | |
G | T | A | (0.0) | (0.4) | 1.00 | 0.00 (0.00–0.00) | |
A | C | A | (0.6) | (0.2) | 0.56 | 2.32 (0.14–37.22) | |
IL-18# | C | G | C | (52.5) | (53.3) | 0.81 | 0.96 (0.68–1.36) |
A | C | G | (25.7) | (27.2) | 0.67 | 0.92 (0.62–1.36) | |
A | G | C | (13.3) | (8.7) | 0.08 | 1.66 (0.96–2.89) | |
C | G | G | (4.1) | (5.7) | 0.45 | 0.72 (0.30–1.17) | |
A | C | C | (1.2) | (2.1) | 0.46 | 0.57 (0.12–2.71) | |
A | G | G | (2.6) | (1.5) | 0.40 | 1.66 (0.52–5.30) | |
C | C | G | (0.0) | (1.1) | 1.00 | 0.00 (0.00–0.00) | |
C | C | C | (0.6) | (0.4) | 0.91 | 1.15 (0.10–12.75) |
Bacteria | Presence | Patients with AgP N = 25 (%) | Controls N = 51 (%) | p | OR 95% CI | Non-Smokers with AgP | Non-Smokers Controls | p | OR 95%CI |
A. actinomycetemcomitans | negative | 16 (64.0) | 37 (72.5) | 10 (71.4) | 33 (73.3) | ||||
positive | 9 (36.0) | 14 (27.5) | 0.31 | 1.49 (0.53–4.13) | 4 (28.6) | 12 (26.7) | 0.57 | 1.10 (0.29–4.18) | |
T. forsythia | negative | 1 (4.0) | 23 (45.1) | 1 (7.1) | 21 (46.7) | ||||
positive | 24 (96.0) | 28 (54.9) | 0.000137 * | 19.71 (2.48–157.03) | 13 (92.9) | 24 (53.3) | 0.0064 | 11.38 (1.37–94.45) | |
P. gingivalis | negative | 4 (16.0) | 42 (82.4) | 1 (7.1) | 37 (82.2) | ||||
positive | 21 (84.0) | 9 (17.6) | <0.000001 * | 24.50 (6.75–88.92) | 13 (92.9) | 8 (17.8) | 0.000001 | 60.13 (6.85–528.08) | |
T. denticola | negative | 3 (12.0) | 28 (54.9) | 1 (7.1) | 25 (55.6) | ||||
positive | 22 (88.0) | 23 (45.1) | 0.000262 * | 8.93 (2.37–33.63) | 13 (92.9) | 20 (44.4) | 0.0012 | 16.25 (1.96–135.01) | |
P. micra | negative | 3 (12.0) | 22 (43.1) | 3 (21.4) | 20 (44.4) | ||||
positive | 22 (88.0) | 29 (56.9) | 0.005410 * | 5.56 (1.48–20.98) | 11 (78.6) | 25 (55.6) | 0.11 | 2.93 (0.72–11.96) | |
P. intermedia | negative | 9 (36.0) | 28 (54.9) | 4 (28.6) | 26 (57.8) | ||||
positive | 16 (64.0) | 23 (45.1) | 0.10 | 2.16 (0.81–5.80) | 10 (71.4) | 19 (42.2) | 0.054 | 3.42 (0.93–12.57) | |
F. nucleatum | negative | 0 (0.0) | 3 (5.9) | 5 (35.7) | 3 (6.67) | ||||
positive | 25 (100.0) | 48 (94.1) | 0.30 | 1.56 (0.15–15.81) | 9 (64.3) | 42 (93.3) | 0.014 | 0.13 (0.03–0.64) |
PBMCs | IL-10 Levels (pg/mL) | p | ||
---|---|---|---|---|
Median | IQR | Minimum–Maximum | ||
Unstimulated (negative control) | 1.8 | 0.4–6.2 | 0–13.9 | |
With PWM (positive control) | 85.7 | 61.7–302.0 | 14.4–3447.0 | 0.00013 |
Stimulated by bacteria | ||||
A. actinomycetemcomitans | 30.1 | 15.9–136.9 | 4.4–663.1 | 0.00009 |
T. forsythia | 75.9 | 29.2–173.6 | 0.6–320.1 | 0.00035 |
P. gingivalis | 0.7 | 0.2–5.0 | 0.0–45.7 | 0.287 |
P. intermedia | 5.3 | 2.3–13.0 | 0.0–173.6 | 0.034 (Pcorr > 0.05) |
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Borilova Linhartova, P.; Danek, Z.; Deissova, T.; Hromcik, F.; Lipovy, B.; Szaraz, D.; Janos, J.; Fassmann, A.; Bartova, J.; Drizhal, I.; et al. Interleukin Gene Variability and Periodontal Bacteria in Patients with Generalized Aggressive Form of Periodontitis. Int. J. Mol. Sci. 2020, 21, 4728. https://doi.org/10.3390/ijms21134728
Borilova Linhartova P, Danek Z, Deissova T, Hromcik F, Lipovy B, Szaraz D, Janos J, Fassmann A, Bartova J, Drizhal I, et al. Interleukin Gene Variability and Periodontal Bacteria in Patients with Generalized Aggressive Form of Periodontitis. International Journal of Molecular Sciences. 2020; 21(13):4728. https://doi.org/10.3390/ijms21134728
Chicago/Turabian StyleBorilova Linhartova, Petra, Zdenek Danek, Tereza Deissova, Filip Hromcik, Bretislav Lipovy, David Szaraz, Julius Janos, Antonin Fassmann, Jirina Bartova, Ivo Drizhal, and et al. 2020. "Interleukin Gene Variability and Periodontal Bacteria in Patients with Generalized Aggressive Form of Periodontitis" International Journal of Molecular Sciences 21, no. 13: 4728. https://doi.org/10.3390/ijms21134728