TLR4 Receptor D299G/T399I Haplotype Polymorphism Is Associated with Insulin Resistance in Obese Female Subjects
Abstract
:1. Introduction
2. Methods
2.1. Study Protocol
2.2. Study Design
2.3. Anthropometrics Measurements
2.4. Biochemical Assays
2.5. Genotyping of the Polymorphisms of the Variants rs4986790 and rs4986791
2.6. Flowcytometry and Expression of TLR4 Receptors on Monocytes and Macrophages
2.7. Definitions and Cut-Off Values in the Study
2.8. Statistical Analysis
2.9. Power Calculations
3. Results
3.1. Phenotype Characteristics: Anthropometric and Biochemical Data of the Study Subjects
3.2. TLR4 Genetic and Haplotype Distribution and Its Association with Obesity Phenotypes
3.3. Linkage Disequilibrium (LD) of the Two SNPs (rs4986791 and rs4986790) in Study Subjects
3.4. The Frequency Distribution of the Metabolic Syndrome among the Study Subjects
3.5. Association between Obesity Phenotypes and Dominant Genetic Models of rs4986790 and SNP rs4986791 among the Study Subjects
3.6. rs4986791 and rs4986790 Polymorphisms-Related Odds Ratios with MS Components and Lipid Profile
3.7. Haplotype Frequency and Its Association with Obesity, WC, HOMA and Dyslipidemia
3.8. The Expression of CD284 of TLR4 in Study Subjects by Flow Cytometry
3.9. Association between CD284 of TLR4 and the Genotype and Haplotype Distribution of Two SNPs (rs4986791 and rs4986790)
3.10. The Correlation between Haplotype of Two SNPs (rs4986791 and rs4986790) and IL6, IL10, and CD284 of Monocyte TLR4 Expression
4. Discussion
5. Plain Summary
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Variables | NON-Obese (n = 132) | Obese (n = 66) | p-Value |
---|---|---|---|
Age (years) | 22.04 ± 3.39 | 21.45 ± 2.67 | 0.215 |
BMI (kg/m2) | 22.72 ± 3.60 | 35.65 ± 4.01 | <0.0001 |
WC (cm) | 80.26 ± 9.01 | 102.88 ± 8.22 | <0.0001 |
%BF | 33.91 ± 7.04 | 48.06 ± 3.43 | <0.0001 |
Systolic blood pressure (mmHg) | 114.24 ± 6.10 | 121.27 ± 8.40 | 0.785 |
Diastolic blood pressure (mmHg) | 72.25 ± 4.45 | 78.55 ± 7.85 | 0.425 |
Glucose (mmol/L) | 4.95 ± 0.43 | 5.06 ± 0.71 | 0.251 |
TC (mmol/L) | 3.95 ± 0.26 | 4.03 ± 0.93 | 0.032 |
TG (mmol/L) | 0.79 ± 0.37 | 0.93 ± 0.68 | 0.121 |
HDL-C (mmol/L) | 1.37 ± 0.36 | 0.90 ± 0.39 | <0.0001 |
LDL-C (mmol/L) | 2.35 ± 0.80 | 2.19 ± 1.59 | 0.386 |
hsCRP (pg/mL) | 1.19 (0.21–4.01) | 4.94 (1.66–7.78) | 0.001 |
Insulin (μU/L) | 10.68 (4.71–15.54) | 16.05 (5.50–19.25) | <0.0001 |
HOMA (insulin resistance) (IR) | 1.83 (1.08–3.53) | 3.67 (1.87–4.74) | <0.0001 |
Leptin (ng/mL) | 8.19 (3.36–13.12) | 20.25 (17.18–37.82) | 0.038 |
SNP | Genotype | All Subjects (n = 197) | NON-Obese (n = 131) | Obese (n = 66) | p-Value |
rs4986791 (+1196 C > T) Thr399Ile | CC | 178 (90.4%) | 117 (89.3%) | 61 (92.4%) | 0.485 |
CT | 19 (9.6%) | 14 (10.7%) | 5 (7.6%) | ||
Minor allele frequency (T) | 0.048 | 0.053 | 0.038 | 0.493 | |
SNP | Genotype | All Subjects (n = 198) | NON-Obese (n = 132) | Obese (n = 66) | p-Value |
rs4986790 (+896 A > G) Asp299Gly | AA | 173 (87.4%) | 117 (88.4%) | 56 (86.4%) | 0.452 |
AG | 12 (6%) | 4 (4.2%) | 8 (7.8%) | ||
GG | 13 (6.6%) | 11(7.4%) | 2 (5.8%) | ||
Minor allele frequency (G) | 0.096 | 0.098 | 0.090 | 0.809 |
Variables | Non-Obese (n = 21) | Obese (n = 21) | p-Value |
---|---|---|---|
TLR4 Mean Fluorescent Intensity (MFI) | 2536.00 ± 641.60 | 3444.00 ± 461.30 | <0.0001 |
IL-6 (pg/mL) | 1.31 ± 0.35 | 12.42 ± 3.41 | <0.0001 |
IL-10 (pg/mL) | 3.91 ± 0.64 | 2.56 ± 0.52 | 0.045 |
SNP | Genotype | All Subjects (n = 42) | Non-Obese (n = 21) | Obese (n = 21) | p-Value |
rs4986791 (+1196C > T) Thr399Ile | CC | 38(90.5%) | 19(90.5%) | 19 (90.5%) | 1.000 |
CT | 4 (9.5%) | 2 (10.5%) | 2 (10.5%) | ||
SNP | Genotype | All Subjects (n = 42) | Non-Obese (n = 21) | Obese (n = 21) | p-Value |
rs4986790 (+896A > G) Asp299Gly | AA | 35 (83.3%) | 17 (80.9%) | 18 (85.7%) | 0.506 |
AG | 3 (7.1%) | 1 (4.8%) | 2 (9.5%) | ||
GG | 4 (9.5%) | 3 (14.3%) | 1 (4.8%) | ||
Haplotype | All Subjects (n = 42) | Non-Obese (n = 21) | Obese (n = 21) | p-Value | |
rs4986790 (+896A > G) Asp299Gly | CA | 35 (83.3%) | 17 (80.9%) | 18 (85.7%) | 0.834 |
CG | 3 (7.1%) | 2 (9.5%) | 1(4.8%) | ||
TG | 4 (9.5%) | 2 (9.5%) | 2(9.5%) |
Genotype | Monocyte CDTLR4 Expression | ||
---|---|---|---|
rs4986791 | Low expression group (≥25%) (n = 11) | High expression group (≥75%) (n = 10) | p-Value |
CC | 10 (90.9%) | 8 (80.0%) | 0.486 |
CT | 1(9.1%) | 2 (20.0%) | |
rs4986790 | |||
AA | 9 (81.8%) | 7 (70.0%) | 0.281 |
AG | 0 (0.0%) | 2 (20.0%) | |
GG | 2 (18.2%) | 1 (10.0%) | |
Haplotype rs4986790 & rs4986790 | Low expression group (≥25%) (n = 11) | High expression group (≥75%) (n = 10) | p-Value |
CA | 9 (81.8%) | 7 (70.0%) | 0.765 |
AG | 1 (9.1%) | 1 (10.0%) | |
TG | 1 (9.1%) | 2 (20.0%) |
IL-6 | IL-10 | TLR4 | Haplotype | |
---|---|---|---|---|
Variables | r p | r p | r p | r p |
IL-6 | 1 | −0.675 <0.0001 | 0.595 <0.0001 | 0.036 0.819 |
IL-10 | −0.675 <0.0001 | 1 | −0.654 <0.0001 | 0.009 0.095 |
TLR4 | 0.595 <0.0001 | −0.654 <0.0001 | 1 | 0.324 0.0598 |
Haplotype | 0.036 0.819 | 0.009 0.095 | 0.324 0.0598 | 1 |
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Sharif, E.; Al-Wakeel, M.; Mohamed, A.; kerkadi, A.; Rizk, N. TLR4 Receptor D299G/T399I Haplotype Polymorphism Is Associated with Insulin Resistance in Obese Female Subjects. Genes 2020, 11, 814. https://doi.org/10.3390/genes11070814
Sharif E, Al-Wakeel M, Mohamed A, kerkadi A, Rizk N. TLR4 Receptor D299G/T399I Haplotype Polymorphism Is Associated with Insulin Resistance in Obese Female Subjects. Genes. 2020; 11(7):814. https://doi.org/10.3390/genes11070814
Chicago/Turabian StyleSharif, Elham, Mariam Al-Wakeel, Afnan Mohamed, Abdelhamid kerkadi, and Nasser Rizk. 2020. "TLR4 Receptor D299G/T399I Haplotype Polymorphism Is Associated with Insulin Resistance in Obese Female Subjects" Genes 11, no. 7: 814. https://doi.org/10.3390/genes11070814
APA StyleSharif, E., Al-Wakeel, M., Mohamed, A., kerkadi, A., & Rizk, N. (2020). TLR4 Receptor D299G/T399I Haplotype Polymorphism Is Associated with Insulin Resistance in Obese Female Subjects. Genes, 11(7), 814. https://doi.org/10.3390/genes11070814