TRPA1 Polymorphisms Modify the Hypotensive Responses to Propofol with No Change in Nitrite or Nitrate Levels
Abstract
:1. Introduction
2. Materials and Methods
2.1. Subjects and Study Design
2.2. Measurement of Plasma Nitrite and Plasma Nitrate Concentrations
2.3. Genotyping
2.4. Haplotype Inference
2.5. Statistical Analysis
3. Results
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Characteristics | Total (n = 164) |
---|---|
Male/female | 70/94 |
Age (years) (mean ± SD) | 55 ± 14 |
Ethnicity (Caucasian Yes/No) | 134/30 |
Body mass index (kg/m2) (mean ± SD) | 25.9 ± 4.7 |
Total cholesterol (mg/dL (mean ± SD) | 192 ± 48 |
Glucose (mg/dL) (mean ± SD) | 96 ± 19 |
Urea (mg/dL) (mean ± SD) | 32 ± 12 |
Creatinine (mg/dl) (mean ± SD) | 0.90 ± 0.3 |
Potassium (mM) (mean ± SD) | 4.3 ± 0.5 |
Hemoglobin (g/dL) (mean ± SD) | 12.7± 1.9 |
Total propofol use (mg) (mean ± SD) | 192 ± 68 |
Mean blood pressure (mmHg) (mean ± SD) | |
Baseline | 93.7 ± 16.5 |
After propofol | 75.6 ± 15.8 * |
Systolic blood pressure (mmHg) (mean ± SD) | |
Baseline | 133 ± 19.7 |
After propofol | 105 ± 18.2 * |
Diastolic blood pressure (mmHg) (mean ± SD) | |
Baseline | 76.8 ± 15.6 |
After propofol | 64.1 ± 15.6 * |
Heart rate (beats/min) (mean ± SD) | |
Baseline | 81.4 ± 13.8 |
After propofol | 79.4 ± 14.1 |
Change in SBP (mmHg) | Change in MBP (mmHg) | Change in DBP (mmHg) | |||||||
---|---|---|---|---|---|---|---|---|---|
Rs920829 | R2 = 0.40 RMSE = 15.00 | R2 = 0.28 RMSE = 12.20 | R2 = 0.23 RMSE = 11.90 | ||||||
Source | ß | 95% CI | p | ß | 95% CI | p | ß | 95% CI | p |
Use of ACEi | +1.64 | −6.65 to 9.94 | 0.695 | −2.18 | −8.84 to 4.47 | 0.518 | −1.36 | −7.87 to 5.15 | 0.680 |
Age (years) | −0.02 | −0.24 to 0.19 | 0.804 | −0.04 | −0.21 to 0.13 | 0.636 | +0.00 | −0.15 to 0.17 | 0.943 |
BMI (kg/m2) | +0.58 | −0.05 to 1.21 | 0.071 | +0.72 | 0.21 to 1.24 | <0.006 * | +0.67 | 0.17 to 1.18 | 0.009 * |
BBP | −0.61 | −0.76 to −0.47 | <0.001 * | −0.43 | −0.56 to −0.31 | <0.001 * | −0.40 | −0.53 to −0.27 | <0.001 * |
TC | −3.61 | −10.09 to 2.65 | 0.251 | −2.65 | −7.83 to 2.51 | 0.311 | −2.77 | −7.83 to 2.29 | 0.281 |
Change in SBP (mmHg) | Change in MBP (mmHg) | Change in DBP (mmHg) | |||||||
---|---|---|---|---|---|---|---|---|---|
Rs16937976 | R2 = 0.42 RMSE = 15.40 | R2 = 0.32 RMSE = 11.80 | R2 = 0.26 RMSE = 11.70 | ||||||
Source | ß | 95% CI | p | ß | 95% CI | p | ß | 95% CI | p |
Use of ACEi | +0.97 | −7.49 to 9.44 | 0.820 | −1.98 | −8.43 to 4.45 | 0.543 | −1.20 | −7.60 to 5.18 | 0.709 |
Age (years) | −0.11 | −0.33 to 0.11 | 0.318 | −0.04 | −0.20 to 0.12 | 0.612 | +0.00 | −0.15 to 0.16 | 0.954 |
BMI (kg/m2) | +1.20 | 0.55 to 1.85 | <0.001 * | +0.82 | 0.32 to 1.13 | 0.001 * | +0.75 | 0.25 to 1.25 | 0.003 * |
BBP | −0.62 | −0.77 to −0.47 | <0.001 * | −0.44 | −0.56 to −0.32 | <0.001 * | −0.40 | −0.53 to −0.28 | <0.001 * |
CG (+GG) | +7.53 | 1.62 to 13.43 | 0.013 * | +7.15 | 2.61 to 11.70 | 0.002 * | +5.18 | 0.67 to 9.70 | 0.025 * |
Change in SBP (mmHg) | Change in MBP (mmHg) | Change in DBP (mmHg) | |||||||
---|---|---|---|---|---|---|---|---|---|
Rs13218757 | R2 = 0.42 RMSE = 15.30 | R2 = 0.33 RMSE = 11.70 | R2 = 0.26 RMSE = 11.70 | ||||||
Source | ß | 95% CI | p | ß | 95% CI | p | ß | 95% CI | p |
Use of ACEi | +0.82 | −7.62 to 9.26 | 0.848 | −2.13 | −8.55 to 4.27 | 0.511 | −1.31 | −7.70 to 5.07 | 0.685 |
Age (years) | −0.10 | −0.32 to 0.11 | 0.339 | −0.03 | −0.20 to 0.12 | 0.637 | +0.00 | −0.15 to 0.16 | 0.932 |
BMI (kg/m2) | +1.24 | 0.59 to 1.89 | <0.001 * | +0.86 | 0.36 to 1.36 | <0.001 * | +0.77 | 0.28 to 1.27 | 0.002 * |
BBP | −0.62 | −0.77 to −0.47 | <0.001 * | −0.44 | −0.56 to −0.31 | <0.001 * | −0.40 | −0.53 to −0.27 | <0.001 * |
AG (+AA) | +8.11 | 2.12 to 14.10 | 0.008 * | +7.66 | 3.06 to 12.27 | 0.001 * | +5.62 | 1.04 to 10.21 | 0.016 * |
Change in SBP (mmHg) | Change in MBP (mmHg) | Change in DBP (mmHg) | |||||||
---|---|---|---|---|---|---|---|---|---|
R2 = 0.39 RMSE = 15.40 | R2 = 0.28 RMSE = 11.70 | R2 = 0.24 RMSE = 11.70 | |||||||
Source | ß | 95% CI | p | ß | 95% CI | p | ß | 95% CI | p |
Use of ACEi | −0.74 | −4.78 to 6.27 | 0.790 | −1.46 | −5.64 to 2.72 | 0.493 | +0.10 | −4.06 to 4.26 | 0.962 |
Age (years) | −0.09 | −0.23 to 0.05 | 0.207 | −0.07 | −0.17 to 0.03 | 0.199 | −0.00 | −0.11 to 0.09 | 0.877 |
BMI (kg/m2) | +0.98 | +0.56 to 1.41 | <0.001 * | +0.72 | 0.39 to 1.04 | <0.001 * | +0.63 | 0.31 to 0.95 | <0.001 * |
BBP | −0.60 | −0.70 to −0.50 | <0.001 * | −0.40 | −0.49 to −0.32 | <0.001 * | −0.38 | −0.47 to 0.30 | <0.001 * |
Haplotypes | |||||||||
CGA | +6.04 | 0.90 to 11.08 | 0.021 * | +5.74 | 1.81 to 9.67 | 0.004 * | +4.55 | 0.65 to 8.45 | 0.022 * |
CGG | +3.73 | −27.16 to 34.63 | 0.812 | +2.02 | −21.58 to 25.62 | 0.866 | −0.04 | −23.52 to 23.42 | 0.997 |
TCG | +0.41 | −5.58 to 6.41 | 0.892 | −1.27 | −5.854 to 3.31 | 0.586 | −1.90 | −5.64 to 3.45 | 0.636 |
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de Melo, I.B.; Oliveira-Paula, G.H.; Ferezin, L.P.; Ferreira, G.C.; Pinheiro, L.C.; Tanus-Santos, J.E.; Garcia, L.V.; Lacchini, R.; Paula-Garcia, W.N. TRPA1 Polymorphisms Modify the Hypotensive Responses to Propofol with No Change in Nitrite or Nitrate Levels. Curr. Issues Mol. Biol. 2022, 44, 6333-6345. https://doi.org/10.3390/cimb44120432
de Melo IB, Oliveira-Paula GH, Ferezin LP, Ferreira GC, Pinheiro LC, Tanus-Santos JE, Garcia LV, Lacchini R, Paula-Garcia WN. TRPA1 Polymorphisms Modify the Hypotensive Responses to Propofol with No Change in Nitrite or Nitrate Levels. Current Issues in Molecular Biology. 2022; 44(12):6333-6345. https://doi.org/10.3390/cimb44120432
Chicago/Turabian Stylede Melo, Isabela Borges, Gustavo H. Oliveira-Paula, Letícia Perticarrara Ferezin, Graziele C. Ferreira, Lucas C. Pinheiro, Jose E. Tanus-Santos, Luis V. Garcia, Riccardo Lacchini, and Waynice N. Paula-Garcia. 2022. "TRPA1 Polymorphisms Modify the Hypotensive Responses to Propofol with No Change in Nitrite or Nitrate Levels" Current Issues in Molecular Biology 44, no. 12: 6333-6345. https://doi.org/10.3390/cimb44120432