Frequency of Tumor Necrosis Factor-α, Interleukin-6, and Interleukin-10 Gene Polymorphisms in Mexican Patients with Diabetic Retinopathy and Diabetic Kidney Disease
Abstract
:1. Introduction
2. Materials and Methods
2.1. Samples and Data Collection
2.2. Genotyping
2.3. Statistical Analyses
3. Results
3.1. Clinical Features
3.2. Polymorphisms
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
T2D | Type 2 diabetes mellitus |
DR | Diabetic retinopathy |
DKD | Diabetic kidney disease |
SNP | Single nucleotide polymorphism |
TNF-α | Tumor necrosis factor-α |
IL-6 | Interleukin-6 |
IL-10 | Interleukin-10 |
BMI | Body mass index |
HbA1c | Glycosylated hemoglobin |
AHT | Arterial hypertension |
LDL | Low density lipids |
HDL | High density lipids |
OR | Odds ratio |
CI | Confidence interval |
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SNP ID | Forward and Reverse Primer ID | Forward and Reverse Primer Sequence | Extended Primer ID | Extended Primer Sequence |
---|---|---|---|---|
TNF-α rs361525_W1 | rs361525_W1_F | ACGTTGGATGCACACAAATCAGTCAGTGGC | rs361525_W1_E | cccctACCCCCCTCGGAATC |
rs361525_W1_R | ACGTTGGATGTCTCGGTTTCTTCTCCATCG | |||
TNF-α rs1800629_W1 | rs1800629_W1_F | ACGTTGGATGGCATCCTGTCTGGAAGTTAG | rs1800629_W1_E | AGGCTGAACCCCGTCC |
rs1800629_W1_R | ACGTTGGATGCTGATTTGTGTGTAGGACCC | |||
IL-10 rs1800872_W1 | rs1800872_W1_F | ACGTTGGATGTCCTCAAAGTTCCCAAGCAG | rs1800872_W1_E | cccccGACTGGCTTCCTACAG |
rs1800872_W1_R | ACGTTGGATGAAGAGGTGGAAACATGTGCC | |||
IL-10 rs1800871_W1 | rs1800871_W1_F | ACGTTGGATGATGCTAGTCAGGTAGTGCTC | rs1800872_W1_E | cccccGACTGGCTTCCTACAG |
rs1800871_W1_R | ACGTTGGATGGTACAGTAGGGTGAGGAAAC | |||
SNP ID | Forward and reverse Primer ID | Forward and Reverse Primer Sequence | Labelled probes | |
IL-10 rs1800896 | rs1800896-F | ATGGAGGCTGGATAGGAGGT | rs1800896-T | [HEX]-CCTACTTCCCCTTCCCAAAG-[MGB] |
rs1800896-R | CACACACACACACAAATCCAAG | rs1800896-C | [FAM]-CCTACTTCCCCCTCCCAAAG-[MGB] | |
IL-6 rs1800795 | rs1800795-F | CGACCTAAGCTGCACTTTTCC | rs1800795-Wild-type | [Cy5]TTGTGTCTTGCGATGCTA[BHQ-2] |
rs1800795-R | AGATTGTGCAATGTGACGTCCTT | rs1800795-Mutant | [FAM]TTGTGTCTTGCCATGCTA[BHQ-1] |
Variable | T2D with Microvascular Complications n = 102 | T2D Without Microvascular Complications n = 101 | Statistical Significance & | T2D with DR n = 95 | T2D Without DR n = 108 | Statistical Significance & | T2D with DKD n = 50 | T2D Without DKD n = 153 | Statistical Significance & |
---|---|---|---|---|---|---|---|---|---|
Age, years | 58.53 ± 12.53 | 53.71 ± 14.50 | 0.012 | 58.18 ± 12.25 | 54.33 ± 14.73 | 0.046 | 61.36 ± 8.47 | 54.42 ± 14.68 | 6.45 × 10−5 |
Sex | |||||||||
Female (%) | 33 (32.4) | 43 (42.6) | 0.132 | 28 (29.5) | 47 (43.5) | 0.042 | 13 (26.0) | 62 (40.5) | 0.065 |
Male (%) | 69 (67.6) | 58 (57.4) | 67 (70.5) | 61 (56.5) | 37 (74.0) | 91 (59.5) | |||
BMI (Kg/m2) | 28.46 ± 4.22 | 25.03 ± 3.22 | 6.60 × 10−10 | 28.40 ± 4.22 | 25.30 ± 3.46 | 5.15 × 10−8 | 26.62 ± 3.63 | 26.80 ± 4.28 | 0.788 |
Weight (Kg) | 79.56 ± 15.76 | 67.23 ± 6.61 | 2.43 × 10−11 | 80.10 ± 16.03 | 67.55 ± 6.88 | 9.52 × 10−11 | 73.70 ± 11.00 | 73.33 ± 14.34 | 0.850 |
T2D time (years) | 12.87 ± 5.28 | 14.27 ± 5.15 | 0.058 | 13.29 ± 5.18 | 13.81 ± 5.32 | 0.490 | 13.66 ± 4.68 | 13.54 ± 5.43 | 0.885 |
DR time (years) | 5.57 ± 2.74 | ||||||||
DKD time (years) | 3.06 ± 1.65 | ||||||||
HbA1c (%) | 9.09 ± 2.06 | 8.00 ± 2.35 | 5.47 × 10−4 | 9.19 ± 2.06 | 7.98 ± 2.30 | 1.19 × 10−4 | 9.69 ± 2.48 | 8.17 ± 2.07 | 2.82 × 10−5 |
Fasting glucose (mg/dL) | 152.43 ± 33.99 (8.46 mmol/L) | 135.69 ± 23.35 (7.53 mmol/L) | 6.47 × 10−5 | 153.85 ± 33.95 (8.54 mmol/L) | 135.53 ± 23.71 (7.52 mmol/L) | 1.93 × 10−5 | 155.64 ± 34.84 (8.64 mmol/L) | 140.33 ± 27.76 (7.79 mmol/L) | 6.10 × 10−3 |
LDL (mg/dL) | 89.32 ± 28.22 | 97.74 ± 28.51 | 0.036 | 89.44 ± 28.53 | 97.08 ± 28.34 | 0.057 | 91.68 ± 26.40 | 94.11 ± 29.36 | 0.604 |
HDL (mg/dL) | 42.84 ± 11.41 | 43.25 ± 9.15 | 0.777 | 43.11 ± 11.59 | 42.98 ± 9.13 | 0.9322 | 41.84 ± 10.92 | 43.43 ± 10.13 | 0.345 |
Triglicerids (mg/dL) | 204.38 ± 137.70 | 190.27 ± 84.51 | 0.379 | 206.37 ± 141.79 | 189.44 ± 82.88 | 0.3090 | 199.24 ± 137.35 | 196.75 ± 106.21 | 0.907 |
AHT | |||||||||
Yes (%) | 62 (60.8) | 30 (29.7%) | 8.67 × 10−6 | 58 (61.1) | 34 (31.5%) | 2.41 × 10−5 | 30 (60.0) | 62 (40.5%) | 0.016 |
No (%) | 40 (39.2) | 71 (70.3%) | 37 (38.9) | 74 (68.5%) | 20 (40.0) | 91 (59.5%) | |||
Smoking | |||||||||
Yes (%) | 42 (41.2) | 35 (34.7) | 0.338 | 40 (42.1) | 37 (34.3) | 0.295 | 23 (46.0) | 54 (35.3) | 0.176 |
No (%) | 60 (58.8) | 66 (65.3) | 55 (57.9) | 71 (65.7) | 27 (54.0) | 99 (64.7) |
T2D with VS. Without Microvascular Complications | T2D with VS. Without DR | T2D with VS. Without DKD | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Polymorphisms | Allele/Genotype | Cases (%) | Controls (%) | p | OR (95%CI) * | Cases (%) | Controls (%) | p | OR (95%CI) * | Cases (%) | Controls (%) | p | OR (95%CI) * |
TNF-α | |||||||||||||
rs361525 | G | 98.04 | 100 | 0.05 | --- | 97.89 | 100 | 0.03 | --- | 99 | 99.01 | 0.995 | 0.99 (0.10–9.66) |
A | 1.96 | 0 | 0.05 | --- | 2.11 | 0 | 0.03 | --- | 1 | 0.99 | 0.995 | 1.01 (0.10–9.79) | |
Codominant | G/G | 96.08 | 100 | 0.05 | --- | 95.79 | 100 | 0.03 | --- | 98 | 98.01 | 0.995 | 0.99 (0.10–9.77) |
G/A | 3.92 | 0 | 0.05 | --- | 4.21 | 0 | 0.03 | --- | 2 | 1.99 | 0.995 | 1.01 (0.10–9.90) | |
rs1800629 | G | 89.71 | 96.46 | 0.01 | 0.32 (0.13–0.77) | 89.47 | 96.23 | 0.01 | 0.33 (0.14–0.378 | 96 | 92.05 | 0.179 | 2.07 (0.70–6.12) |
A | 10.29 | 3.54 | 0.01 | 3.13 (1.29–7.54) | 10.53 | 3.77 | 0.01 | 1.00 (1.29–6.98) | 4 | 7.95 | 0.179 | 0.48 (0.16–1.42) | |
Codominant | G/G | 79.41 | 92.93 | 0.01 | 0.29 (0.12–0.73) | 78.95 | 92.45 | 0.01 | 0.31 (0.13–0.73) | 92 | 84.11 | 0.162 | 2.17 (0.72–6.60) |
G/A | 20.59 | 7.07 | 0.01 | 3.41 (1.37–8.43) | 21.05 | 7.55 | 0.01 | 3.27 (1.36–7.82) | 8 | 15.89 | 0.162 | 0.46 (0.15–1.39) | |
IL-10 | |||||||||||||
rs1800872 | G | 58.33 | 54.04 | 0.39 | 1.19 (0.80–1.77) | 57.89 | 54.72 | 0.52 | 1.14 (0.77–1.69) | 63 | 53.97 | 0.115 | 1.45 (0.91–2.31) |
T | 41.67 | 45.96 | 0.39 | 0.84 (0.57–1.25) | 42.11 | 45.28 | 0.52 | 0.88 (0.59–1.30) | 37 | 46.03 | 0.115 | 0.69 (0.43–1.09) | |
Codominant | G/G | 25.49 | 25.25 | 0.97 | 1.01 (0.54–1.91) | 24.21 | 26.42 | 0.72 | 0.89 (0.47–1.68) | 32 | 23.18 | 0.214 | 1.56 (0.77–3.15) |
G/T | 65.69 | 57.58 | 0.24 | 1.41 (0.79–2.49) | 67.37 | 56.6 | 0.12 | 1.58 (0.89–2.81) | 62 | 61.59 | 0.959 | 1.02 (0.53–1.97) | |
T/T | 8.82 | 17.17 | 0.08 | 1.47 (0.19–1.10) | 8.42 | 16.98 | 0.07 | 0.45 (0.19–1.09) | 6 | 15.23 | 0.092 | 0.35 (0.10–1.24) | |
rs1800871 | G | 58.33 | 54.04 | 0.39 | 1.19 (0.80–1.77) | 57.89 | 54.72 | 0.52 | 1.14 (0.77–1.69) | 63 | 53.97 | 0.115 | 1.45 (0.91–2.31) |
A | 41.67 | 45.96 | 0.39 | 0.84 (0.57–1.25) | 42.11 | 45.28 | 0.52 | 0.88 (0.59–1.30) | 37 | 46.03 | 0.115 | 0.69 (0.43–1.09) | |
Codominant | G/G | 25.49 | 25.25 | 0.97 | 1.01 (0.54–1.91) | 24.21 | 26.42 | 0.72 | 0.89 (0.47–1.68) | 32 | 23.18 | 0.214 | 1.56 (0.77–3.15) |
G/A | 65.69 | 57.58 | 0.24 | 1.41 (0.79–2.49) | 67.37 | 56.6 | 0.12 | 1.58 (0.89–2.81) | 62 | 61.59 | 0.959 | 1.02 (0.53–1.97) | |
A/A | 8.82 | 17.17 | 0.08 | 0.47 (0.19–1.10) | 8.42 | 16.98 | 0.07 | 0.44 (0.19–1.09) | 6 | 15.23 | 0.092 | 0.36 (0.10–1.24) | |
rs1800896 | T | 67.65 | 78.28 | 0.02 | 0.58 (0.37–0.91) | 67.37 | 77.83 | 0.02 | 0.59 (0.38–0.92) | 58 | 77.81 | 1 × 10−4 | 0.39 (0.24–0.64) |
C | 32.35 | 21.72 | 0.02 | 1.72 (1.10–2.69) | 32.63 | 22.17 | 0.02 | 1.70 (1.09–2.65) | 42 | 22.19 | 1 × 10−4 | 2.54 (1.57–4.11) | |
Codominant | T/T | 44.12 | 57.58 | 0.06 | 0.58 (0.33–1.01) | 44.21 | 56.6 | 0.08 | 0.61 (0.35–1.06) | 28 | 58.28 | 2 × 10−4 | 0.28 (0.14–0.56) |
T/C | 47.06 | 41.41 | 0.42 | 1.26 (0.72–2.19) | 46.32 | 42.45 | 0.58 | 1.16 (0.67–2.04) | 60 | 39.07 | 0.009 | 2.34 (1.22–4.49) | |
C/C | 8.82 | 1.01 | 0.01 | 9.48 (1.18–76.33) | 9.47 | 0.94 | 0.01 | 10.99 (1.37–88.45) | 12 | 2.65 | 0.008 | 5.01 (1.35–18.56) | |
Recesive | C/C | 8.82 | 1.01 | 0.01 | 9.48 (1.18–76.33) | 9.47 | 0.94 | 0.01 | 10.99 (1.37–88.45) | 12 | 2.65 | 0.008 | 5.04 (1.35–18.56) |
T/C+T/T | 91.18 | 98.99 | 0.01 | 0.11 (0.01–0.85) | 90.53 | 99.06 | 0.01 | 0.09 (0.01–0.73) | 88 | 97.35 | 0.008 | 0.19 (0.05–0.73) | |
IL-6 | |||||||||||||
rs1800795 | G | 93.14 | 91.92 | 0.64 | 1.19 (0.57–2.51) | 93.16 | 91.98 | 0.65 | 1.19 (0.56–2.51) | 88 | 94.04 | 0.046 | 0.46 (0.21–1.00) |
C | 6.86 | 8.08 | 0.64 | 0.84 (0.39–1.77) | 6.84 | 8.02 | 0.65 | 0.84 (0.39_1.78) | 12 | 5.96 | 0.046 | 2.15 (0.99–4.64) | |
Codominant | G/G | 89.22 | 83.84 | 0.26 | 1.59 (0.70–3.63) | 89.47 | 83.96 | 0.25 | 1.62 (0.70–3.74) | 82 | 88.08 | 0.274 | 0.61 (0.26–1.48) |
G/C | 7.84 | 16.16 | 0.07 | 0.44 (1.79–1.08) | 7.37 | 16.04 | 0.06 | 0.42 (0.16–1.05) | 12 | 11.92 | 0.988 | 1.00 (0.37–2.69) | |
C/C | 2.94 | 0 | 0.09 | --- | 3.16 | 0 | 0.07 | --- | 6 | 0 | 0.002 | --- |
T2D with VS. Without Microvascular Complications | T2D with VS. Without DR | T2D with VS. Without DR | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Haplotypes | Cases (%) | Controls (%) | p | OR (95%CI) * | Cases (%) | Controls (%) | p | OR (95%CI) * | Cases (%) | Controls (%) | p | OR (95%CI) * |
TNF-α rs361525-rs1800629 | ||||||||||||
GG | 88 | 96.46 | 0 | 0.27 (0.11–0.65) | 89.68 | 96.23 | 0.002 | 0.28 (0.12–0.65) | 95.8 | 91.06 | 0.124 | 2.23 (0.78–6.42) |
GA | 9.9 | 3.54 | 0.01 | 2.99 (1.24–7.25) | 10.32 | 3.77 | 0.012 | 2.87 (1.23–6.70) | 3.2 | 7.95 | 0.101 | 0.38 (0.12–1.26) |
IL-10 rs1800872-rs1800871-rs1800896 | ||||||||||||
TAT | 41 | 45.2 | 0.38 | 0.84 (0.56–1.24) | 41.61 | 44.87 | 0.509 | 0.88 (0.59–1.30) | 36.6 | 45.1 | 0.137 | 2.21 (0.44–1.12) |
GGT | 27 | 33.08 | 0.17 | 0.74(0.48–1.14) | 26.33 | 33.56 | 0.116 | 0.71 (0.46–1.09) | 21.4 | 32.72 | 0.032 | 0.56 (0.33–0.96) |
GGC | 32 | 20.96 | 0.02 | 1.74 (1.10–2.73) | 32.06 | 21.58 | 0.018 | 1.71 (1.09–2.68) | 41.6 | 21.26 | 6 × 10−5 | 2.64 (1.63–4.28) |
T2D with VS. Without Microvascular Complications | T2D with VS. Without DR | T2D with VS. Without DKD | ||||
---|---|---|---|---|---|---|
Variable | p | OR (95%CI) * | p | OR (95%CI) * | p | OR (95%CI) * |
AHT | 1.30 × 10−4 | 6.25 (2.45–16.00) | 1.23 × 10−3 | 3.95 (1.72–9.09) | 5.91 × 10−4 | 6.43 (2.22–18.59) |
Smoking | --- | --- | --- | --- | 0.043 | 2.66 (1.03–6.85) |
Age | 2.43 × 10−3 | 1.08 (1.03–1.14) | --- | --- | 0.021 | 1.06 (1.01–1.11) |
T2D Time | 8.16 × 10−5 | 0.81 (0.73–0.90) | --- | --- | 1.93 × 10−3 | 0.85 (0.77–0.94) |
Weight | 1.10 × 10−7 | 1.13 (1.08–1.19) | 6.04 × 10−8 | 1.12 (1.08–1.17) | 3.67 × 10−4 | 1.13 (1.06–1.22) |
BMI | --- | --- | --- | --- | 1.80 × 10−3 | 0.67 (0.52–0.86) |
HbA1C | 8.11 × 10−5 | 1.51 (1.23–1.86) | 7.86 × 10−6 | 1.52 (1.27–1.83) | 3.85 × 10−5 | 1.69 (1.32–2.17) |
rs361525AG | --- | --- | --- | --- | 0.045 | 0.021 (4.8 × 10−4–0.91) |
rs1800896CC | 1.52 × 10−2 | 32.42 (1.96–537.70) | 1.76 × 10−3 | 39.36 (3.94–393.29) | 9.47 × 10−5 | 59.46 (7.65–462.41) |
rs1800896TC | 1.06 × 10−2 | 4.14 (1.39–12.33) | 8.55 × 10−4 | 4.08 (1.79–9.33) | 4.56 × 10−4 | 7.51 (2.43–23.16) |
rs1800795GC | --- | --- | --- | --- | 1.36 × 10−2 | 7.04 (1.49–33.18) |
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Sánchez-Valencia, P.E.; Díaz-García, J.D.; Leyva-Leyva, M.; Sánchez-Aguillón, F.; González-Arenas, N.R.; Mendoza-García, J.G.; Tenorio-Aguirre, E.K.; de León-Bautista, M.P.; Ibarra-Arce, A.; Maravilla, P.; et al. Frequency of Tumor Necrosis Factor-α, Interleukin-6, and Interleukin-10 Gene Polymorphisms in Mexican Patients with Diabetic Retinopathy and Diabetic Kidney Disease. Pathophysiology 2025, 32, 14. https://doi.org/10.3390/pathophysiology32020014
Sánchez-Valencia PE, Díaz-García JD, Leyva-Leyva M, Sánchez-Aguillón F, González-Arenas NR, Mendoza-García JG, Tenorio-Aguirre EK, de León-Bautista MP, Ibarra-Arce A, Maravilla P, et al. Frequency of Tumor Necrosis Factor-α, Interleukin-6, and Interleukin-10 Gene Polymorphisms in Mexican Patients with Diabetic Retinopathy and Diabetic Kidney Disease. Pathophysiology. 2025; 32(2):14. https://doi.org/10.3390/pathophysiology32020014
Chicago/Turabian StyleSánchez-Valencia, Patricia Elvira, Juan Daniel Díaz-García, Margarita Leyva-Leyva, Fabiola Sánchez-Aguillón, Nelly Raquel González-Arenas, Jesús Guillermo Mendoza-García, Erika Karina Tenorio-Aguirre, Mercedes Piedad de León-Bautista, Aurora Ibarra-Arce, Pablo Maravilla, and et al. 2025. "Frequency of Tumor Necrosis Factor-α, Interleukin-6, and Interleukin-10 Gene Polymorphisms in Mexican Patients with Diabetic Retinopathy and Diabetic Kidney Disease" Pathophysiology 32, no. 2: 14. https://doi.org/10.3390/pathophysiology32020014
APA StyleSánchez-Valencia, P. E., Díaz-García, J. D., Leyva-Leyva, M., Sánchez-Aguillón, F., González-Arenas, N. R., Mendoza-García, J. G., Tenorio-Aguirre, E. K., de León-Bautista, M. P., Ibarra-Arce, A., Maravilla, P., & Olivo-Díaz, A. (2025). Frequency of Tumor Necrosis Factor-α, Interleukin-6, and Interleukin-10 Gene Polymorphisms in Mexican Patients with Diabetic Retinopathy and Diabetic Kidney Disease. Pathophysiology, 32(2), 14. https://doi.org/10.3390/pathophysiology32020014