The Effect Sizes of PPARγ rs1801282, FTO rs9939609, and MC4R rs2229616 Variants on Type 2 Diabetes Mellitus Risk among the Western Saudi Population: A Cross-Sectional Prospective Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Genotyping
2.3. Statistical Analysis
3. Results
3.1. The Association of PPARγ rs1801282, FTO rs9939609, and MC4R rs2229616 Variants with T2DM Risk
3.2. Relative Risk for T2DM from Alleles in PPARγ rs1801282, FTO rs9939609, and MC4R rs2229616 SNPs
3.3. Associations of Categorical Factors with the Risk of T2DM in PPARγ rs1801282, FTO rs9939609, and MC4R rs2229616 SNP Genotypes
3.4. The Risk for T2DM from Combined Polygenic SNPs, PPARγ rs1801282, FTO rs9939609, or MC4R rs2229616
4. Discussion
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Variable | Category |
---|---|
Obesity (BMI) (kg/m2) | Non-Obese (<25) |
Obese (≥25) | |
FBS (mmol/l) | Controllable (<7) |
Uncontrollable (≥7) | |
HbA1c (%) | Controllable (<7) |
Uncontrollable (≥7) | |
Triglyceride level (mmol/l) | Desirable (<2.2) |
High risk (≥2.2) | |
Cholesterol level (mmol/l) | Desirable (<6.2) |
High risk (≥6.2) |
Variable | Control Sample (n = 323) | Diabetic Sample (n = 415) | p-Value |
---|---|---|---|
Age (years) | 34.4 ± 15.5 | 56.2 ± 12.9 | <0.001 |
Height (cm) | 162.5± 9.8 | 162.5 ± 9.1 | 0.970 |
Weight (kg) | 67.9 ± 18.5 | 77.6 ± 15.2 | <0.001 |
BMI (kg/m2) | 25.3 ± 6.1 | 30.1 ± 7.0 | <0.001 |
FBS (mmol/l) | 5.9 ± 2.1 | 8.2 ± 3.6 | <0.001 |
HbA1c (%) | 6.0 ± 1.1 | 8.2 ± 2.0 | <0.001 |
Triglycerides (mmol/l) | 0.74 ± 0.49 | 1.1 ± 0.75 | <0.001 |
Cholesterol (mmol/l) | 4.73 ± 1.14 | 4.66 ± 1.16 | 0.654 |
SNP | Genotype | Genotype Frequency (CTRL) | Genotype Frequency (T2DM) | p-Value | Minor Allele | 1000-Genome MAF | CTRL MAF | T2DM MAF |
---|---|---|---|---|---|---|---|---|
PPARγ rs1801282 Pro12Ala | C/C | 225 (83.6%) | 308 (87.3%) | 0.348 | G | 0.07 | 0.08 | 0.07 |
C/G | 38 (14.1%) | 41 (11.6%) | ||||||
G/G | 6 (2.2%) | 4 (1.1%) | ||||||
FTO rs9939609 intronic variant | A/A | 51 (16.2%) | 73 (20.0%) | 0.367 | A | 0.34 | 0.39 | 0.46 |
A/T | 168 (53.3%) | 194 (53.0%) | ||||||
T/T | 96 (30.5%) | 99 (27%) | ||||||
MC4R rs2229616 Val103Ile | C/C | 170 (75.9%) | 337 (98.3%) | <0.001 | T | 0.016 | 0.12 | 0.01 |
C/T | 52 (23.2%) | 6 (1.7%) | ||||||
T/T | 2 (0.9%) | 0 (0%) |
SNP | Allele | Allele Frequency (T2DM) | Allele Frequency (CTRL) | RR | OR | p-Value |
---|---|---|---|---|---|---|
PPARγ rs1801282 | C G | 657 49 | 488 50 | 1.16 | 1.37 | 0.139 |
FTO rs9939609 | A T | 340 392 | 270 360 | 1.07 | 1.16 | 0.190 |
MC4R rs2229616 | C T | 680 6 | 392 56 | 6.56 | 16.19 | <0.0001 |
SNP | Factors | Genotype | p-Value | OR | 95% C.I. for OR | |
---|---|---|---|---|---|---|
Lower | Upper | |||||
PPARγ rs1801282 Pro12Ala | T2DM | C/C | 0.269 | 2.05 | 0.57 | 7.36 |
C/G | 0.481 | 1.62 | 0.42 | 6.18 | ||
Obesity (BMI) ≥ 25 | C/C | 0.592 | 1.72 | 0.24 | 12.38 | |
C/G | 0.806 | 1.29 | 0.17 | 10.15 | ||
HbA1c (%) | C/C | 0.999 | 0.0 | - | - | |
C/G | 0.999 | 0.0 | - | - | ||
FBS (mmol/l) | C/C | 1.000 | 0.0 | 0.0 | - | |
C/G | 1.000 | 0.0 | 0.0 | - | ||
Triglyceride level (mmol/l) | C/C | 1.000 | 0.0 | - | - | |
Cholesterol level (mmol/l) | C/C | - | - | - | - | |
FTO rs9939609 intronic variant | T2DM | A/A | 0.158 | 1.39 | 0.88 | 2.19 |
A/T | 0.525 | 1.12 | 0.79 | 1.59 | ||
Obesity (BMI) ≥ 25 | A/A | 0.882 | 0.95 | 0.49 | 1.85 | |
A/T | 0.580 | 0.86 | 0.51 | 1.46 | ||
HbA1c (%) | A/A | 0.431 | 1.97 | 0.37 | 10.59 | |
A/T | 0.618 | 1.34 | 0.42 | 4.27 | ||
FBS (mmol/l) | A/A | 0.697 | 1.36 | 0.29 | 6.32 | |
A/T | 0.276 | 2.18 | 0.54 | 8.80 | ||
Triglyceride level (mmol/l) | A/A | 0.999 | - | 0.0 | - | |
A/T | 0.826 | 1.40 | 0.07 | 28.12 | ||
Cholesterol level (mmol/l) | A/A | 0.427 | 0.33 | 0.02 | 5.03 | |
A/T | 0.196 | 3.67 | 0.51 | 26.22 | ||
MC4R rs2229616 Val103Ile | T2DM | C/C | 0.999 | - | - | - |
C/T | 0.999 | - | - | - | ||
Obesity (BMI) ≥ 25 | C/C | 1.000 | - | - | - | |
C/T | 1.000 | - | - | - | ||
HbA1c (%) | C/C | 0.999 | 0.0 | 0.0 | - | |
FBS (mmol/l) | C/C | 1.000 | 0.0 | 0.0 | - | |
Triglyceride level (mmol/l) | C/C | - | - | - | - | |
Cholesterol level (mmol/l) | C/C | - | - | - | - |
Combined SNPs Genotypes | p-Value | OR | 95% C.I. for OR | |
---|---|---|---|---|
Lower | Upper | |||
PPARγ rs1801282 (C/C) by FTO rs9939609 (A/A) by MC4R rs2229616 (C/C) | 0.045 * | 1.82 | 1.01 | 3.27 |
PPARγ rs1801282 (C/C) by FTO rs9939609 (A/A) by MC4R rs2229616 (C/T) | 0.084 | 1.45 | 0.95 | 2.20 |
PPARγ rs1801282 (C/C) by FTO rs9939609 (A/T) by MC4R rs2229616 (C/C) | 0.097 | 0.25 | 0.05 | 1.29 |
PPARγ rs1801282 (C/C) by FTO rs9939609 (A/T) by MC4R rs2229616 (C/T) | 0.002 ** | 0.04 | 0.01 | 0.30 |
PPARγ rs1801282 (C/T) by FTO rs9939609 (A/A) by MC4R rs2229616 (C/C) | 0.827 | 0.88 | 0.28 | 2.74 |
PPARγ rs1801282 (C/T) by FTO rs9939609 (A/A) by MC4R rs2229616 (C/T) | 0.829 | 0.91 | 0.37 | 2.22 |
PPARγ rs1801282 (C/T) by FTO rs9939609 (A/T) by MC4R rs2229616 (C/T) | 1.000 | 0.00 | 0.000 | - |
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Bakhashab, S.; Filimban, N.; Altall, R.M.; Nassir, R.; Qusti, S.Y.; Alqahtani, M.H.; Abuzenadah, A.M.; Dallol, A. The Effect Sizes of PPARγ rs1801282, FTO rs9939609, and MC4R rs2229616 Variants on Type 2 Diabetes Mellitus Risk among the Western Saudi Population: A Cross-Sectional Prospective Study. Genes 2020, 11, 98. https://doi.org/10.3390/genes11010098
Bakhashab S, Filimban N, Altall RM, Nassir R, Qusti SY, Alqahtani MH, Abuzenadah AM, Dallol A. The Effect Sizes of PPARγ rs1801282, FTO rs9939609, and MC4R rs2229616 Variants on Type 2 Diabetes Mellitus Risk among the Western Saudi Population: A Cross-Sectional Prospective Study. Genes. 2020; 11(1):98. https://doi.org/10.3390/genes11010098
Chicago/Turabian StyleBakhashab, Sherin, Najlaa Filimban, Rana M. Altall, Rami Nassir, Safaa Y. Qusti, Mohammed H. Alqahtani, Adel M. Abuzenadah, and Ashraf Dallol. 2020. "The Effect Sizes of PPARγ rs1801282, FTO rs9939609, and MC4R rs2229616 Variants on Type 2 Diabetes Mellitus Risk among the Western Saudi Population: A Cross-Sectional Prospective Study" Genes 11, no. 1: 98. https://doi.org/10.3390/genes11010098