The KDR Gene rs2071559 and the VEGF Gene rs6921438 May Be Associated with Diabetic Nephropathy in Caucasians with Type 2 Diabetes Mellitus
Abstract
:1. Introduction
2. Results
2.1. Clinical Characteristics
2.2. Genetical Data
2.3. Immunohistochemical Data
3. Discussion
4. Materials and Methods
4.1. Patients
4.2. Biochemical Analyses
4.3. Genotyping
4.4. Immunohistochemistry
4.5. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Cases (N = 344) | Controls (N = 553) | p-Value | |
---|---|---|---|
Sex [M] | 201 (58.4%) | 318 (57.5%) | 0.78 |
Age [years] | 65.35 ± 9.37 | 65.43 ± 8.63 | 0.90 |
Duration of T2D [years] | 15.69 ± 7.64 | 13.99 ± 7.00 | <0.001 |
Duration of hypertension [years] | 13.65 ± 8.92 | 12.18 ± 7.83 | 0.020 |
SBP [mmHg] | 155.08 ± 19.4 | 148.45 ± 19.61 | <0.001 |
DBP [mmHg] | 84.45 ± 11.55 | 83.09 ± 10.40 | 0.071 |
BMI | 30.91 ± 4.45 | 30.25 ± 4.52 | 0.031 |
Active smokers | 32 (9.3%) | 70 (12.7%) | 0.12 |
CVD | 89 (25.9%) | 165 (29.8%) | 0.20 |
Family history of CVD | 0.14 | ||
No | 286 (83.1%) | 449 (81.2%) | |
Yes (before 55 of age) | 22 (6.4%) | 25 (4.5%) | |
Yes (after 55 of age) | 36 (10.5%) | 79 (14.3%) | |
DR | 149 (43.3%) | 115 (20.8%) | <0.001 |
Duration of DR [years] | 5.00 (4.00–7.00) | 5.00 (5.00–8.00) | 0.23 |
Dneuropathy | 69 (20.1%) | 39 (7.1%) | <0.001 |
DF | 62 (18.0%) | 40 (7.2%) | <0.001 |
S-HbA1c [%] 1 | 7.93 ± 0.28 | 7.65 ± 1.14 | 0.002 |
S-fasting glucose [mmol/L] | 8.80 (7.25–10.60) | 8.10 (6.80–9.70) | <0.001 |
S-Hb [g/L] | 138.55 ± 14.17 | 138.98 ± 12.88 | 0.69 |
S-urea [mmol/L] | 6.40 (5.40–8.20) | 6.00 (4.90–7.60) | <0.001 |
S-creatinine [µmol/L] | 82.00 (68.00–105.00) | 77.00 (66.00–91.50) | <0.001 |
Male sex | 93.00 (75.00–109.00) | 84.00 (70.00–98.00) | <0.001 |
Female sex | 73.00 (57.00–95.25) | 70.00 (61.00–82.00) | 0.041 |
eGFR [MDRD equation, mL/min] | 75.00 (60.00–90.00) | 76.00 (60.00–90.00) | 0.15 |
Male sex | 93.00 (75.00–109.00) | 84.00 (70.00–98.00) | <0.001 |
Female sex | 73.00 (57.00–95.25) | 70.00 (61.00–82.00) | 0.041 |
S-cystatinC [mg/L] | 0.82 (0.69–1.04) | 0.75 (0.65–0.86) | <0.001 |
S-Totalcholesterol [mmol/L] | 4.40 (3.80–5.23) | 4.40 (3.90–5.20) | 0.41 |
S-HDL [mmol/L] | 1.20 (1.00–1.40) | 1.20 (1.00–1.40) | 0.83 |
S-LDL [mmol/L] | 2.50 (2.00–3.10) | 2.50 (2.00–3.10) | 0.45 |
S-TGS [mmol/L] | 1.60 (1.10–2.50) | 1.50 (1.00–2.20) | 0.023 |
U-albumin/creatinine ratio [g/moL], sample no. 1 | 8.14 (3.80–23.60) | 0.99 (0.60–1.58) | <0.001 |
U-albumin/creatinine ratio [g/moL], sample no. 2 | 8.26 (3.70–25.10) | 1.02 (0.68–1.70) | <0.001 |
U-albumin/creatinine ratio [g/moL], sample no. 3 | 7.98 (3.82–22.82) | 1.02 (0.68–1.73) | <0.001 |
Cases (N = 344) | Controls (N = 553) | p-Value | |
---|---|---|---|
KDR_rs2071559 | |||
CC | 88 (25.6%) | 122 (22.1%) | 0.034 |
CT | 182 (52.9%) | 269 (48.6%) | |
TT | 74 (21.5%) | 162 (29.3%) | |
KDR_rs2305948 | |||
TT | 2 (0.6%) | 11 (2.0%) | 0.16 |
CT | 73 (21.2%) | 103 (18.6%) | |
CC | 269 (78.2%) | 439 (79.4%) | |
HWE | |||
KDR_rs2071559 | 0.2667 | 0.6048 | |
KDR_rs2305948 | 0.2104 | 0.0950 | |
ALLELES | |||
KDR_rs2071559 | |||
C (MAF) | 358 (52.0%) | 513 (46.4%) | 0.020 |
T | 330 (48.0%) | 593 (53.6%) | |
KDR_rs2305948 | |||
T (MAF) | 77 (11.2%) | 125 (11.3%) | 0.94 |
C | 611 (88.8%) | 981 (88.7%) | |
DOMINANT | |||
KDR_rs2071559 | |||
CC + CT | 270 (78.5%) | 391 (70.7%) | 0.010 |
TT | 74 (21.5%) | 162 (29.3%) | |
KDR_rs2305948 | |||
TT + CT | 75 (21.8%) | 114 (20.6%) | 0.67 |
CC | 269 (78.2%) | 439 (79.4%) | |
RECESSIVE | |||
KDR_rs2071559 | |||
CC | 88 (25.6%) | 122 (22.1%) | 0.23 |
CT + TT | 256 (74.4%) | 431 (77.9%) | |
KDR_rs2305948 | |||
TT | 2 (0.6%) | 11 (2.0%) | 0.086 |
CT + CC | 342 (99.4%) | 542 (98.0%) | |
CT + CC | 342 (99.4%) | 542 (98.0%) |
VEGF_rs6921438 | Cases (N = 344) | Controls (N = 553) | p-Value |
---|---|---|---|
GG | 82 (23.8%) | 180 (32.5%) | 0.007 |
AG | 176 (51.2%) | 271 (49.0%) | |
AA | 86 (25.0%) | 102 (18.4%) | |
ALLELES | |||
G (MAF) | 340 (49.4%) | 631 (57.1%) | 0.002 |
A | 348 (50.6%) | 475 (42.9%) | |
HWE (p-value) | 0.2667 | 0.6048 | |
DOMINANT | |||
GG + AG | 258 (75.0%) | 451 (81.6%) | 0.019 |
AA | 86 (25.0%) | 102 (18.4%) | |
RECESSIVE | |||
GG | 82 (23.8%) | 180 (32.5%) | 0.005 |
AG + AA | 262 (76.2%) | 373 (67.5%) |
KDR_rs20715599 | Count | OR (95% CI) | p-Value for OR |
---|---|---|---|
co-dominant | |||
CC vs. TT | 88/122 vs. 74/162 | 1.61 (1.02–2.56) | 0.042 |
CT vs. TT | 182/269 vs. 74/162 | 1.60 (1.08–2.39) | 0.021 |
dominant | |||
[CC + CT] vs. TT | 270/391 vs. 74/162 | 1.61 (1.11–2.35) | 0.013 |
Recessive | |||
CC vs. [CT + TT] | 88/122 vs. 256/431 | 1.16 (0.79–1.68) | 0.45 |
KDR_rs2305948 | count | OR (95% CI) | p-value for OR |
co-dominant | |||
TT vs. CC | 2/11 vs. 269/439 | 0.21 (0.01–1.38) | 0.17 |
CT vs. CC | 73/103 vs. 269/439 | 1.53 (0.80–2.93) | 0.20 |
dominant | |||
[TT + CT] vs. CC | 75/114 vs. 269/439 | 1.27 (0.69–2.35) | 0.44 |
recessive | |||
TT vs. [CT + CC] | 2/11 vs. 342/542 | 0.21 (0.01–1.32) | 0.16 |
VEGF _rs6921438 | Count | OR (95% CI) | p-Value for OR |
---|---|---|---|
co-dominant | |||
GG vs. AA | 82/180 vs. 86/102 | 0.51 (0.32–0.8) | 0.004 |
AG vs. AA | 176/271 vs. 86/102 | 0.76 (0.5–1.13) | 0.17 |
dominant | |||
[GG + AG] vs. AA | 258/451 vs. 86/102 | 0.66 (0.45–0.96) | 0.030 |
Recessive | |||
GG vs. [AG + AA] | 82/180 vs. 262/373 | 0.61 (0.43–0.88) | 0.009 |
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Nussdorfer, P.; Petrovič, D.; Alibegović, A.; Cilenšek, I.; Petrovič, D. The KDR Gene rs2071559 and the VEGF Gene rs6921438 May Be Associated with Diabetic Nephropathy in Caucasians with Type 2 Diabetes Mellitus. Int. J. Mol. Sci. 2024, 25, 9439. https://doi.org/10.3390/ijms25179439
Nussdorfer P, Petrovič D, Alibegović A, Cilenšek I, Petrovič D. The KDR Gene rs2071559 and the VEGF Gene rs6921438 May Be Associated with Diabetic Nephropathy in Caucasians with Type 2 Diabetes Mellitus. International Journal of Molecular Sciences. 2024; 25(17):9439. https://doi.org/10.3390/ijms25179439
Chicago/Turabian StyleNussdorfer, Petra, David Petrovič, Armin Alibegović, Ines Cilenšek, and Danijel Petrovič. 2024. "The KDR Gene rs2071559 and the VEGF Gene rs6921438 May Be Associated with Diabetic Nephropathy in Caucasians with Type 2 Diabetes Mellitus" International Journal of Molecular Sciences 25, no. 17: 9439. https://doi.org/10.3390/ijms25179439