VEGF Polymorphisms (VEGF-936 C/T, VEGF-634 G/C and VEGF-2578 C/A) and Cardiovascular Implications in Long COVID Patients
Abstract
:1. Introduction
2. Objectives
3. Results
3.1. Patient Characteristics and Demographics
3.2. Effect of VEGF-936 C/T on Cardiovascular Dysfunction and Subclinical Atherosclerosis
3.3. Effect of VEGF-634 G/C on TAPSE (Right Ventricular Dysfunction)
3.4. Effect of VEGF-2578 C/A on Diastolic Function
3.5. Haplotypic Analysis
4. Discussion
5. Materials and Methods
5.1. Study Design
5.2. Sample Collection
5.3. Clinical Assessment
5.4. Genotyping
5.5. Statistical Analysis
6. Conclusions
7. Study Limitations
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Characteristics | Categories/Types | N (%) |
---|---|---|
Sex | Male | 45 (67.16) |
Female | 22 (32.84) | |
Ethnicity | Romanian | 62 (92.53) |
Hungarian | 5 (7.47) | |
Smoking habit | Yes | 18 (26.87) |
No | 49 (73.13) | |
BMI (kg/m2) | Underweight | 3 (4.47) |
Normal | 39 (58.20) | |
Overweight | 17 (25.37) | |
Obese | 8 (11.94) | |
Mean | 24.45 ± 4.64 | |
Comorbidities | History of neoplasia | 2 (2.98) |
Autoimmune disease | 9 (13.43) | |
Liver disease | 6 (8.95) | |
Renal disease | 2 (2.98) | |
Pulmonary disease | 8 (11.94) |
VEGF-936 C/T (rs3025039) | Genotype | Count (Proportion) |
C/C | 42 (0.63) | |
C/T | 19 (0.28) | |
T/T | 6 (0.09) | |
Alleles | Count (Proportion) | |
C | 103 (0.77) | |
T | 31 (0.23) | |
VEGF-634 C/G (rs2010963) | Genotype | Count (Proportion) |
G/G | 58 (0.87) | |
G/C | 9 (0.13) | |
C/C | 0 (0) | |
Alleles | Count (Proportion) | |
G | 125 (0.93) | |
C | 9 (0.07) | |
VEGF-2578 C/A (rs699947) | Genotype | Count (Proportion) |
C/C | 14 (0.21) | |
C/A | 23 (0.34) | |
A/A | 30 (0.45) | |
Alleles | Count (Proportion) | |
C | 51 (0.38) | |
A | 83 (0.62) |
Model | N | Mean (mm) ± SD | Mean Difference | 95% CI | p |
---|---|---|---|---|---|
Co-dominant | |||||
C/C | 17 | 0.045 ± 0.021 | Reference | 0.017 | |
C/T | 10 | 0.010 ± 0.0281 | 0.055 | 0.011–0.121 | |
T/T | 3 | 0.110 ± 0.023 | 0.155 | 0.023–0.155 | |
Dominant | |||||
C/C | 17 | 0.045 ± 0.021 | Reference | 0.022 | |
C/T-T/T | 13 | 0.033 ± 0.025 | 0.014 | 0.014–0.142 | |
Recessive | |||||
C/C-C-T | 27 | 0.024 ± 0.017 | Reference | 0.017 | |
T/T | 3 | 0.110 ± 0.023 | 0.134 | 0.030–0.239 | |
Over-dominant | |||||
C/C-T/T | 20 | 0.022 ± 0.022 | Reference | 0.395 | |
C/T | 10 | 0.010 ± 0.028 | 0.032 | 0.040–0.104 | |
Log-additive | |||||
0, 1, 2 | 0.069 | 0.025–0.114 | 0.004 |
At Baseline | At 6 Months | |||||
---|---|---|---|---|---|---|
β | 95% CI | p | β | 95% CI | p | |
VEGF-936C/T log additive | −3.07 | −5.65–0.48 | 0.024 | −1.85 | −5.4–1.7 | 0.318 |
Age (years) | 0.48 | 0.24–0.72 | <0.001 | 0.52 | 0.27–0.78 | <0.001 |
BMI (kg/m2) | −0.46 | −0.89–−0.02 | 0.044 | −0.79 | −1.26–−0.31 | 0.003 |
Sex (Male vs. Female) | −11.46 | −15.2–−7.73 | <0.001 | −10.93 | −16.7–−5.16 | 0.001 |
SBPao (mmHg) | 0.32 | 0.15–0.5 | <0.001 | 0.32 | (0.06–0.58) | 0.026 |
Smoking (Yes vs. No) | 4.18 | −0.17–8.53 | 0.064 | 1.06 | −4.76–6.88 | 0.724 |
Model | N | Mean (%) ± SD | Mean Difference | 95% CI | p |
---|---|---|---|---|---|
Co-dominant | |||||
C/C | 16 | 54.88 ± 0.90 | Reference | 0.008 | |
C/T | 11 | 59.91 ± 1.29 | 5.034 | 2.089–7.979 | |
T/T | 2 | 58.00 | 3.125 | −2.514–8.764 | |
Dominant | |||||
C/C | 16 | 54.88 ± 0.90 | Reference | 0.002 | |
C/T-T/T | 13 | 59.62 ± 1.10 | 4.740 | 0.014–0.142 | |
Recessive | |||||
C/C-C-T | 27 | 56.93 ± 0.88 | Reference | 0.747 | |
T/T | 2 | 58.00 | 1.074 | −5.3959–7.544 | |
Over-dominant | |||||
C/C-T/T | 18 | 55.22 ± 0.83 | Reference | 0.003 | |
C/T | 11 | 59.91 ± 1.29 | 4.687 | 1.7997–7.574 | |
Log-additive | |||||
0, 1, 2 | 3.202 | 0.856–5.548 | 0.012 |
At Baseline | At 6 Months | |||||
---|---|---|---|---|---|---|
β | 95% CI | p | β | 95% CI | p | |
VEGF-936C/T dominant (CT-TT vs. CC) | −1.15 | −5.53–2.23 | 0.493 | 4.6 | 1.72–7.49 | 0.003 |
SBPao (mmHg) | −0.32 | −0.72–0.08 | 0.111 | 0 | −0.13–0.13 | 0.985 |
BMI (kg/m2) | −0.02 | −0.16–0.13 | 0.818 | −0.31 | −0.64–0.02 | 0.060 |
GLS (%) | −0.09 | −0.88–0.69 | 0.811 | 0.19 | −0.36–0.74 | 0.484 |
E/A | 2.42 | −2.50–7.34 | 0.325 | −3.48 | −9.83–2.87 | 0.267 |
VEGF-936C/T | VEGF-634G/C | VEGF-2578CA | Probability |
---|---|---|---|
C | G | A | 0.428 |
C | G | C | 0.274 |
T | G | A | 0.142 |
T | G | C | 0.089 |
C | C | A | 0.050 |
C | C | C | 0.018 |
T | C | A | <0.001 |
Genetic Variations | Primers | PCR Fragment | Restriction Enzyme | RFLP Fragments |
---|---|---|---|---|
VEGF-936C/T | F: 5′-AAGGAAGAGGAGACTCTGCGCAGAGC-3′ R:5′-TAAATGTATGTATGTGGGTGGGTGTGTCTACAG-3′ | 208 bp | NlaIII | C936 allele: 208 bp T936 allele: 122 bp, 86 bp |
VEGF-634G/C | F: 5′-ATTTATTTTTGCTTGCCATT-3′ R: 5′-GTCTGTCTGTCTGTCCGTCA-3′ | 304 bp | BsmFI | G634 allele: 193, 111 bp C634 allele: 304 pb |
VEGF-2578C/A | F: 5′-GGATGGGGCTGACT AGGTAAGC-3′ R: 5′-AGCCCCCTTTTCCT CCAAC-3′ | 324 pb | BglII | C2758 allele: 324 bp A2758 allele:202 bp, 122 bp |
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Cozma, A.; Sitar-Tăuț, A.V.; Orășan, O.H.; Briciu, V.; Leucuța, D.; Sporiș, N.-D.; Lazăr, A.-L.; Mălinescu, T.-V.; Ganea, A.-M.; Sporiș, B.M.; et al. VEGF Polymorphisms (VEGF-936 C/T, VEGF-634 G/C and VEGF-2578 C/A) and Cardiovascular Implications in Long COVID Patients. Int. J. Mol. Sci. 2024, 25, 8667. https://doi.org/10.3390/ijms25168667
Cozma A, Sitar-Tăuț AV, Orășan OH, Briciu V, Leucuța D, Sporiș N-D, Lazăr A-L, Mălinescu T-V, Ganea A-M, Sporiș BM, et al. VEGF Polymorphisms (VEGF-936 C/T, VEGF-634 G/C and VEGF-2578 C/A) and Cardiovascular Implications in Long COVID Patients. International Journal of Molecular Sciences. 2024; 25(16):8667. https://doi.org/10.3390/ijms25168667
Chicago/Turabian StyleCozma, Angela, Adela Viviana Sitar-Tăuț, Olga Hilda Orășan, Violeta Briciu, Daniel Leucuța, Nicolae-Dan Sporiș, Andrada-Luciana Lazăr, Toma-Vlad Mălinescu, Andreea-Maria Ganea, Bianca Mihaela Sporiș, and et al. 2024. "VEGF Polymorphisms (VEGF-936 C/T, VEGF-634 G/C and VEGF-2578 C/A) and Cardiovascular Implications in Long COVID Patients" International Journal of Molecular Sciences 25, no. 16: 8667. https://doi.org/10.3390/ijms25168667