Clinical Significance of TNFRSF1A36T/C Polymorphism in Cachectic Patients with Chronic Heart Failure
Abstract
:1. Introduction
2. Material and Methods
2.1. Study Group
2.2. Nutritional Assessment and Cachexia Detection
2.3. Statistical Analysis
3. Results
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Perticone, M.; Zito, R.; Miceli, S.; Pinto, A.; Suraci, E.; Greco, M.; Gigliotti, S.; Hribal, M.L.; Corrao, S.; Sesti, G.; et al. Immunity, Inflammation and Heart Failure: Their Role on Cardiac Function and Iron Status. Front. Immunol. 2019, 10, 2315. [Google Scholar] [CrossRef] [Green Version]
- Sobieszek, G.; Powrózek, T.; Mazurek, M.; Skwarek-Dziekanowska, A.; Małecka-Massalska, T. Electrical and Hormonal Bi-omarkers in Cachectic Elderly Women with Chronic Heart Failure. J. Clin. Med. 2020, 9, 1021. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ramani, G.V.; Uber, P.A.; Mehra, M.R. Chronic Heart Failure: Contemporary Diagnosis and Management. Mayo Clin. Proc. 2010, 85, 180–195. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ping, Z.; Aiqun, M.; Jiwu, L.; Liang, S. TNF Receptor 1/2 Predict Heart Failure Risk in Type 2 Diabetes Mellitus Patients. Int. Heart J. 2017, 58, 245–249. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bradham, W.S.; Moe, G.; Wendt, K.A.; Scott, A.A.; Konig, A.; Romanova, M.; Naik, G.; Spinale, F.G. TNF-alpha and myocardial matrix metallo-proteinases in heart failure: Relationship to LV remodeling. Am. J. Physiol. Heart Circ. Physiol. 2002, 282, H1288–1295. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Von Haehling, S.; Schefold, J.C.; Lainscak, M.; Doehner, W.; Anker, S.D. Inflammatory biomarkers in heart failure revisited: Much more than innocent bystanders. Heart Fail. Clin. 2009, 5, 549–560. [Google Scholar] [CrossRef] [PubMed]
- Yue, M.; Huang, P.; Wang, C.; Fan, H.; Tian, T.; Wu, J.; Luo, F.; Fu, Z.; Xia, X.; Zhu, P.; et al. Genetic Variation on TNF/LTA and TNFRSF1A Genes is Associated with Outcomes of Hepatitis C Virus Infection. Immunol. Investig. 2021, 50, 1–11. [Google Scholar] [CrossRef] [PubMed]
- Qasem, A.; Ramesh, S.; Naser, S.A. Genetic polymorphisms in tumour necrosis factor receptors (TNFRSF1A/1B) illustrate dif-ferential treatment response to TNFα inhibitors in patients with Crohn’s disease. BMJ Open Gastroenterol. 2019, 6, e000246. [Google Scholar] [CrossRef]
- Evans, W.J.; Morley, J.E.; Argilés, J.; Bales, C.; Baracos, V.; Guttridge, D.; Jatoi, A.; Kalantar-Zadeh, K.; Lochs, H.; Mantovani, G.; et al. Cachexia: A new definition. Clin. Nutr. 2008, 27, 793–799. [Google Scholar] [CrossRef]
- Gaetano, J. Holm-Bonferroni Sequential Correction: An EXCEL Calculator (1.2) [Microsoft Excel Workbook]. 2013. Available online: https://www.researchgate.net/publication/242331583_Holm-Bonferroni_Sequential_Correction_An_EXCEL_Calculator_-_Ver._1.2 (accessed on 15 February 2021).
- Yoshida, T.; Delafontaine, P. Mechanisms of Cachexia in Chronic Disease States. Am. J. Med Sci. 2015, 350, 250–256. [Google Scholar] [CrossRef] [Green Version]
- Rosetti, F.; de la Cruz, A.; Crispín, J.C. Gene-function studies in systemic lupus erythematosus. Curr. Opin. Rheumatol. 2019, 31, 185–192. [Google Scholar] [CrossRef] [PubMed]
- Fan, Y.; Li, L.-H.; Pan, H.-F.; Tao, J.-H.; Sun, Z.-Q.; Ye, D.-Q. Association of ITGAM polymorphism with systemic lupus erythematosus: A meta-analysis. J. Eur. Acad. Dermatol. Venereol. 2011, 25, 271–275. [Google Scholar] [CrossRef] [PubMed]
- Mann, D.L. Inflammatory mediators and the failing heart: Past, present, and the foreseeable future. Circ. Res. 2002, 91, 988–998. [Google Scholar] [CrossRef]
- Dibbs, Z.I.; Diwan, A.; Nemoto, S.; deFreitas, G.; Abdellatif, M.; Carabello, B.A.; Spinale, F.G.; Feuerstein, G.; Sivasubramanian, N.; Mann, D.L. Targeted Overexpression of Transmembrane Tumor Necrosis Factor Provokes a Concentric Cardiac Hypertrophic Phenotype. Circulation 2003, 108, 1002–1008. [Google Scholar] [CrossRef] [Green Version]
- Diwan, A.; Dibbs, Z.; Nemoto, S.; deFreitas, G.; Carabello, B.A.; Sivasubramanian, N.; Wilson, E.M.; Spinale, F.G.; Mann, D.L. Targeted overexpression of non-cleavable and secreted forms of tumor necrosis factor provokes disparate cardiac phenotypes. Circulation 2004, 109, 262–268. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, X.; Moody, M.R.; Engel, D.J.; Walker, S.; Clubb, F.J.; Sivasubramanian, N.; Mann, D.L.; Reid, M.B. Cardiac-Specific Overexpression of Tumor Necrosis Factor-α Causes Oxidative Stress and Contractile Dysfunction in Mouse Diaphragm. Circulation 2000, 102, 1690–1696. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kubota, T.; McTiernan, C.F.; Frye, C.S.; Slawson, S.E.; Lemster, B.H.; Koretsky, A.P.; Demetris, A.J.; Feldman, A.M. Dilated cardiomy-opathy in transgenic mice with cardiac-specific overexpression of tumor necrosis factor-alpha. Circ. Res. 1997, 81, 627–635. [Google Scholar] [CrossRef]
- Mavri, A.; Bastelica, D.; Poggi, M.; Morange, P.; Peiretti, F.; Verdier, M.; Juhan-Vague, I.; Alessi, M.-C. Polymorphism A36G of the tumor necrosis factor receptor 1 gene is associated with PAI-1 levels in obese women. Thromb. Haemost. 2007, 97, 62–66. [Google Scholar] [CrossRef]
- Cho, J.Y.; Kim, K.H.; Cho, H.-J.; Lee, H.-Y.; Choi, J.-O.; Jeon, E.-S.; Lee, S.E.; Kim, M.-S.; Kim, J.-J.; Hwang, K.-K.; et al. Nutritional risk index as a predictor of mortality in acutely decompensated heart failure. PLoS ONE 2018, 13, e0209088. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gupta, D.; Lis, C.G.; Dahlk, S.L.; Vashi, P.G.; Grutsch, J.F.; Lammersfeld, C.A. Bioelectrical impedance phase angle as a prognostic indicator in advanced pancreatic cancer. Br. J. Nutr. 2004, 92, 957–962. [Google Scholar] [CrossRef] [Green Version]
- Gupta, D.; Lammersfeld, C.A.; Burrows, J.L.; Dahlk, S.L.; Vashi, P.G.; Grutsch, J.F.; Hoffman, S.; Lis, C.G. Bioelectrical impedance phase angle in clinical practice: Implications for prognosis in advanced colorectal cancer. Am. J. Clin. Nutr. 2004, 80, 1634–1638. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gupta, D.; Lammersfeld, C.A.; Vashi, P.G.; King, J.; Dahlk, S.L.; Grutsch, J.F.; Lis, C.G. Bioelectrical impedance phase angle as a prognostic indicator in breast cancer. BMC Cancer 2008, 8, 249. [Google Scholar] [CrossRef] [Green Version]
- Hui, D.; Bansal, S.; Morgado, M.; Dev, R.; Chisholm, G.; Bruera, E. Phase angle for prognostication of survival in patients with advanced cancer: Preliminary findings. Cancer 2014, 120, 2207–2214. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Selberg, O.; Selberg, D. Norms and correlates of bioimpedance phase angle in healthy human subjects, hospitalized patients, and patients with liver cirrhosis. Graefe’s Arch. Clin. Exp. Ophthalmol. 2002, 86, 509–516. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Schwenk, A.; Beisenherz, A.; Römer, K.; Kremer, G.; Salzberger, B.; Elia, M. Phase angle from bioelectrical impedance analysis remains an independent predictive marker in HIV-infected patients in the era of highly active antiretroviral treatment. Am. J. Clin. Nutr. 2000, 72, 496–501. [Google Scholar] [CrossRef] [Green Version]
- Małecka-Massalska, T.; Popiołek, J.; Teter, M.; Homa-Mlak, I.; Dec, M.; Makarewicz, A.; Karakuła-Juchnowicz, H. Application of phase angle for evaluation of the nutrition status of patients with anorexia nervosa. Psychiatr. Pol. 2017, 51, 1121–1131. [Google Scholar] [CrossRef] [PubMed]
Variable | Study Group (n = 142) | |
---|---|---|
Sex | Men | 79 (55.6%) |
Women | 63 (44.4%) | |
NYHA | I | 27 (18.9%) |
II | 38 (26.8%) | |
III | 35 (24.7%) | |
IV | 42 (29.6%) | |
SGA | A | 72 (50.7%) |
B | 57 (40.1%) | |
C | 13 (9.2%) | |
Diabetes mellitus | Yes | 52 (36.6%) |
No | 90 (63.4%) | |
Renal failure | Yes | 49 (34.5%) |
No | 93 (65.5%) | |
Smoking status | Smoker | 87 (61.3%) |
Non-smoker | 55 (38.7%) | |
Continuous Variables | Mean ± SD or Median (25th–75th percentile) | |
Age (years) | 72 ± 13 | |
Weight (kg) | 83.0 ± 18.0 | |
BMI (kg/m2) | 29.6 ± 6.11 | |
Albumin (g/dL) | 3.39 ± 0.61 | |
Triglycerides (mg/dL) | 111 ± 64 | |
Total cholesterol (mg/dL) | 157 ± 45 | |
HDL (mg/dL) | 50 ± 18 | |
LDL (mg/dL) | 86 ± 36 | |
Creatinine (mg/dL) | 1.25 ± 0.49 | |
Hemoglobin (g/dL) | 13.1 ± 2.2 | |
CRP (mg/L) | 6.20 (2.1–35) | |
Systolic blood pressure (mmHg) | 132 ± 24 | |
Diastolic blood pressure (mmHg) | 76 ± 14 | |
EF% | 41 ± 15 | |
NT-proBNP (pg/mL) | 2797 (1212–5145) | |
LVESd (cm) | 4.37 ± 1.0 | |
LVEDd (cm) | 5.43 ± 1.1 | |
LAD (cm) | 4.47 ± 0.8 | |
RVOT (cm) | 3.49 ± 0.50 | |
TAPSE (cm) | 1.97 ± 1.4 | |
PASP (mmHg) | 40.27 ± 12.5 |
Variable | TNFRSF1A Genotypes (n = 142) | ||||
---|---|---|---|---|---|
CC (n = 40; 28.2%) | CT (n = 64; 45.1%) | TT (n = 38; 26.7%) | p | ||
Age (years) | 71 ± 12 | 75 ± 13 | 73 ± 15 | 0.770 | |
Weight (kg) | 82 ± 18 | 83 ± 20 | 80 ± 15 | 0.593 | |
BMI (kg/m2) | 29.44 ± 6.53 | 30.18 ± 6.54 | 28.20 ± 4.72 | 0.638 | |
FM (kg) | 28.1 ± 11.7 | 27.9 ± 13.9 | 25.2 ± 10.2 | 0.931 | |
FFM (kg) | 54.2 ± 14.0 | 55.3 ± 14.1 | 53.7 ± 13.7 | 0.690 | |
Albumin (g/dL) | 3.42 ± 0.65 | 3.40 ± 0.58 | 3.16 ± 0.62 | 0.039 | |
Triglycerides (mg/dL) | 114 ± 69 | 110 ± 68 | 109 ± 46 | 0.936 | |
Total cholesterol (mg/dL) | 157 ± 53 | 157 ± 43 | 153 ± 43 | 0.894 | |
HDL (mg/dL) | 48 ± 18 | 49 ± 18 | 52 ± 20 | 0.377 | |
LDL (mg/dL) | 87 ± 40 | 85 ± 35 | 81 ± 34 | 0.664 | |
Creatinine (mg/dL) | 1.33 ± 0.51 | 1.22 ± 0.47 | 1.26 ± 0.57 | 0.589 | |
Hemoglobin (g/dL) | 13.6 ± 2.1 | 13.7 ± 2.3 | 13.2 ± 1.8 | 0.765 | |
CRP (mg/L) | 4.60 (2–17) | 7.70 (2–24) | 12.43 (5–35) | 0.012 * | |
Systolic blood pressure (mmHg) | 133 ± 23 | 133 ± 24 | 128 ± 25 | 0.533 | |
Diastolic blood pressure (mmHg) | 75 ± 14 | 76 ± 13 | 75 ± 16 | 0.860 | |
EF% | 43 ± 15 | 43 ± 15 | 36 ± 14 | 0.033 | |
NT-proBNP (pg/mL) | 2077 (1140–4573) | 2697 (1176–4119) | 3953 (1894–8982) | 0.015 * | |
LVESd (cm) | 4.50 ± 1.13 | 4.24 ± 0.88 | 4.47 ± 1.06 | 0.357 | |
LVEDd (cm) | 5.59 ± 1.16 | 5.28 ± 0.95 | 5.53 ± 0.96 | 0.266 | |
LAD (cm) | 4.46 ± 0.56 | 4.43 ± 0.62 | 4.57 ± 0.51 | 0.553 | |
RVOT (cm) | 3.44 ± 0.54 | 3.45 ± 0.54 | 3.59 ± 0.32 | 0.388 | |
TAPSE (cm) | 2.13 ± 2.23 | 1.84 ± 0.40 | 2.02 ± 1.34 | 0.572 | |
PASP (mmHg) | 38 ± 13 | 40 ± 13 | 42 ± 12 | 0.389 | |
NYHA | I | 13 (48.1%) | 12 (44.4%) | 2 (7.5%) | 0.236 |
II | 8 (21.1%) | 23 (60.5%) | 7 (18.4%) | ||
III | 11 (31.4%) | 14 (40%) | 10 (28.6%) | ||
IV | 8 (19.1%) | 15 (35.7%) | 19 (45.2%) | ||
I and II | 21 (32.3%) | 35 (53.8%) | 9 (13.9%) | 0.006 * | |
III and IV | 19 (24.6%) | 29 (37.7%) | 29 (37.7%) | ||
SGA | A | 23 (31.9%) | 37 (59.7%) | 12 (8.4%) | <0.001 * |
B | 16 (28.1%) | 26 (45.6%) | 15 (26.3%) | ||
C | 1 (7.7%) | 1 (7.7%) | 11 (84.6%) | ||
A | 23 (31.9%) | 37 (59.7%) | 12 (8.4%) | 0.022 | |
B and C | 17 (24.3%) | 27 (38.6%) | 26 (37.1%) | ||
Diabetes mellitus | Yes | 16 (30.8%) | 25 (48.1%) | 11 (21.1%) | 0.516 |
No | 24 (26.7%) | 39 (43.3%) | 27 (30%) | ||
Renal failure | Yes | 14 (28.6%) | 23 (46.9%) | 12 (22.5%) | 0.902 |
No | 26 (28%) | 41 (44%) | 26 (28%) | ||
Smoking status | Smoker | 29 (33.3%) | 38 (43.7%) | 20 (23%) | 0.181 |
Non-smoker | 11 (20%) | 26 (47.3%) | 18 (32.7%) | ||
Cm (nF) | Men | 1.18 (0.78–1.97) | 1.41 (0.77–1.92) | 1.38 (0.71–1.72) | 0.845 |
Women | 1.05 (0.79–2.20) | 1.30 (0.94–1.64) | 1.07 (0.73–1.73) | 0.803 | |
Pa (o) | Men | 4.05 ± 1.06 | 4.31 ± 1.26 | 3.24 ± 1.02 | 0.035 |
Women | 4.54 ± 1.69 | 4.15 ± 1.11 | 3.26 ± 1.14 | 0.032 | |
Z200/Z5 | Men | 0.870 (0.75–0.87) | 0.861 (0.82–0.89) | 0.864 (0.84–0.89) | 0.516 |
Women | 0.859 (0.78–0.89) | 0.853 (0.83–0.87) | 0.853 (0.83–0.88) | 0.930 |
Variable | Study Group (n = 142) | |||
---|---|---|---|---|
Cachectic (n = 60) | Non-Cachectic (n = 82) | p | ||
Age (years) | 76 ± 10 | 72 ± 13 | 0.342 | |
Weight (kg) | 78 ± 20 | 87 ± 15 | 0.005 * | |
BMI (kg/m2) | 28.21 ± 6.36 | 30.76 ± 5.66 | 0.017 * | |
FM (kg) | 25.94 ± 14.52 | 28.05 ± 11.88 | 0.426 | |
FFM (kg) | 52.66 ± 14.01 | 55.26 ± 14.83 | 0.368 | |
Albumin (g/dL) | 2.99 ± 0.59 | 3.72 ± 0.40 | <0.001 * | |
Triglycerides (mg/dL) | 104 ± 55 | 117 ± 70 | 0.253 | |
Total cholesterol (mg/dL) | 153 ± 51 | 160 ± 40 | 0.380 | |
HDL (mg/dL) | 48 ± 19 | 52 ± 17 | 0.251 | |
LDL (mg/dL) | 85 ± 40 | 86 ± 33 | 0.771 | |
Creatinine (mg/dL) | 1.36 ± 0.56 | 1.17 ± 0.43 | 0.033 | |
Hemoglobin (g/dL) | 12.6 ± 2.3 | 13.5 ± 2.0 | 0.019 * | |
CRP (mg/L) | 15.0 (6.0–34.5) | 3.6 (1.7–8.3) | <0.001 * | |
Systolic blood pressure (mmHg) | 132 ± 24 | 132 ± 23 | 0.877 | |
Diastolic blood pressure (mmHg) | 77 ± 15 | 74 ± 12 | 0.324 | |
EF% | 38 ± 12 | 43 ± 15 | 0.022 | |
NT-proBNP (pg/mL) | 4445 (2483–8374) | 1750 (985–3323) | <0.001 * | |
LVESd (cm) | 4.31 ± 1.06 | 4.43 ± 0.95 | 0.481 | |
LVEDd (cm) | 5.34 ± 1.12 | 5.50 ± 0.93 | 0.355 | |
LAD (cm) | 4.52 ± 0.62 | 4.43 ± 0.54 | 0.373 | |
RVOT (cm) | 3.50 ± 0.48 | 3.47 ± 0.52 | 0.790 | |
TAPSE (cm) | 1.78 ± 0.47 | 2.04 ± 1.61 | 0.212 | |
PASP (mmHg) | 43.4 ± 0.2 | 42.1 ± 0.1 | 0.645 | |
Cm (nF) | Men | 1.04 (0.82–1.70) | 1.36 (0.80–1.97) | 0.812 |
Women | 1.05 (0.84–1.40) | 1.42 (1.05–1.86) | 0.109 | |
PA (°) | Men | 3.47 ± 1.14 | 4.13 ± 1.23 | 0.029 |
Women | 3.46 ± 1.20 | 4.56 ± 0.97 | 0.004 * | |
Z200/Z5 | Men | 0.86 (0.83–0.89) | 0.87 (0.84–0.90) | 0.240 |
Women | 0.87 (0.85–0.90) | 0.85 (0.83–0.86) | 0.148 | |
SGA | A | 10 (13.9%) | 62 (86.1%) | <0.001 * |
B | 42 (73.7%) | 15 (26.3%) | ||
C | 8 (61.5%) | 5 (38.5%) | ||
TNFRSF1A genotype | CC | 14 (30.4%) | 32 (69.6%) | 0.013 * |
CT | 25 (41%) | 36 (59%) | ||
TT | 22 (62.9%) | 13 (37.1%) |
Predictors (Independent Variables) | Univariate Regression Analysis | ||
---|---|---|---|
p | OR | [95%CI] | |
Albumin < 3.20 g/dL | <0.001 | 13.6 | [4.35–45.40] |
BMI < 24.9 | 0.004 | 4.32 | [1.59–11.76] |
Renal failure | 0.003 | 3.14 | [1.47–6.17] |
PA < 3.15° | 0.022 | 2.75 | [1.16–6.51] |
SGA B or C | <0.001 | 12.5 | [5.23–29.98] |
TT genotype of TNFRSF1A | 0.019 | 4.23 | [1.37–10.98] |
Predictors (independed variables) | Multivariable regression analysis | ||
p | OR | [95%CI] | |
Albumin < 3.20 g/dL | 0.005 | 7.69 | [1.81–30.3] |
Renal failure | 0.017 | 4.40 | [1.30–14.92] |
TT genotype of TNFRSF1A | 0.036 | 2.56 | [0.64–10.42] |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Sobieszek, G.; Powrózek, T.; Skwarek-Dziekanowska, A.; Małecka-Massalska, T. Clinical Significance of TNFRSF1A36T/C Polymorphism in Cachectic Patients with Chronic Heart Failure. J. Clin. Med. 2021, 10, 1095. https://doi.org/10.3390/jcm10051095
Sobieszek G, Powrózek T, Skwarek-Dziekanowska A, Małecka-Massalska T. Clinical Significance of TNFRSF1A36T/C Polymorphism in Cachectic Patients with Chronic Heart Failure. Journal of Clinical Medicine. 2021; 10(5):1095. https://doi.org/10.3390/jcm10051095
Chicago/Turabian StyleSobieszek, Grzegorz, Tomasz Powrózek, Aneta Skwarek-Dziekanowska, and Teresa Małecka-Massalska. 2021. "Clinical Significance of TNFRSF1A36T/C Polymorphism in Cachectic Patients with Chronic Heart Failure" Journal of Clinical Medicine 10, no. 5: 1095. https://doi.org/10.3390/jcm10051095
APA StyleSobieszek, G., Powrózek, T., Skwarek-Dziekanowska, A., & Małecka-Massalska, T. (2021). Clinical Significance of TNFRSF1A36T/C Polymorphism in Cachectic Patients with Chronic Heart Failure. Journal of Clinical Medicine, 10(5), 1095. https://doi.org/10.3390/jcm10051095