Dietary Protein and Fat Intake Affects Diabetes Risk with CDKAL1 Genetic Variants in Korean Adults
Abstract
:1. Introduction
2. Results
2.1. General Characteristics of the Study Population in Cases and Controls
2.2. Association of SNPs in CDKAL1 Gene with Fasting Blood Glucose and Glycated Hemoglobin
2.3. Associations between CDKAL1 SNPs and Diabetes in Korean Population
2.4. Interactions of SNP and Protein Intake (% Energy) in Relation to the Risk of Diabetes
2.5. Interactions of SNP and Fat Intake (% Energy) in Relation to the Risk of Diabetes
3. Discussion
4. Materials and Methods
4.1. Study Population
4.2. General Characteristics, Anthropometric Measurements, and Biochemical Variables
4.3. Diabetes Detection
4.4. Dietary Measurements
4.5. Genotyping
4.6. Statistical Analyses
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
SNP | Single Nucleotide Polymorphism |
CDKAL1 | Cyclin-Dependent Kinase 5 Regulatory Subunit-Associated Protein 1-Like 1 |
HEXA Study | Health Examinees Study |
GWAS | Genome-Wide Association Study |
KoGES | Korean Genome and Epidemiology Study |
BMI | Body Mass Index |
HOMA-β | The Homeostasis Model Assessment of β-Cell Function |
BDNF | Brain-Derived Neurotrophic Factor |
TCF7L2 | Transcription Factor 7-Like 2 |
HDL-Cholesterol | High Density Lipoprotein-Cholesterol |
TG | Triglyceride |
HbA1c | Glycated Hemoglobin |
OR | Odds Ratio |
AOR | Adjusted Odds Ratio |
CI | Confidence Interval |
MAF | Minor Allele Frequency |
SE | Standard Error |
HR | Hazard Ratio |
PLIN | Perilipin |
KDA | Korean Diabetes Association |
FFQ | Food Frequency Questionnaire |
HWE | Hardy-Weinberg Equilibrium |
IRB | Institutional Review Board |
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Men (n = 2034) | Women (n = 1954) | Total (n = 3988) | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
No Diabetes (n = 737) | Diabetes (n = 1297) | p-Value 1 | No Diabetes (n = 747) | Diabetes (n = 1207) | p- Value 1 | No Diabetes (n = 1484) | Diabetes (n = 2504) | p-Value 1 | |||||||
Age (years) | 64.1 ± 3.0 | 58.1 ± 7.4 | <0.001 | 63.6 ± 2.9 | 57.8 ± 6.9 | <0.001 | 63.9 ± 2.9 | 58.0 ± 7.1 | <0.001 | ||||||
Smoking Status | <0.001 | 0.046 | <0.001 | ||||||||||||
Current | 113 | 15.3% | 340 | 26.2% | 7 | 0.9% | 30 | 2.5% | 120 | 8.1% | 370 | 14.8% | |||
Past | 390 | 52.9% | 609 | 47.0% | 6 | 0.8% | 12 | 1.0% | 396 | 26.7% | 621 | 24.8% | |||
None | 234 | 31.8% | 348 | 26.8% | 734 | 98.3% | 1165 | 96.5% | 968 | 65.2% | 1513 | 60.4% | |||
Physical Activity | 0.278 | 0.180 | 0.747 | ||||||||||||
No | 250 | 33.9% | 471 | 36.3% | 345 | 46.2% | 520 | 43.1% | 595 | 40.1% | 991 | 39.6% | |||
Yes | 487 | 66.1% | 826 | 63.7% | 402 | 53.8% | 687 | 56.9% | 889 | 59.9% | 1513 | 60.4% | |||
Alcohol Use | 0.49 | 0.091 | 0.822 | ||||||||||||
Current | 504 | 68.4% | 903 | 69.6% | 151 | 20.2% | 227 | 18.8% | 655 | 44.1% | 1130 | 45.1% | |||
Past | 76 | 10.3% | 113 | 8.7% | 8 | 1.1% | 29 | 2.4% | 84 | 5.7% | 142 | 5.7% | |||
None | 157 | 21.3% | 281 | 21.7% | 588 | 78.7% | 951 | 78.8% | 745 | 50.2% | 1232 | 49.2% | |||
HDL-Cholesterol (mg/dL) | 51.6 ± 12.4 | 46.4 ± 11.0 | < 0.001 | 55.4 ± 13.3 | 50.0 ± 11.4 | <0.001 | 53.5 ± 13.0 | 48.1 ± 11.4 | < 0.001 | ||||||
Triglyceride (mg/dL) | 128.5 ± 81.3 | 171.3 ± 135.3 | < 0.001 | 120.4 ± 69.3 | 151.3 ± 101.5 | <0.001 | 124.5 ± 75.6 | 161.6 ± 120.6 | < 0.001 | ||||||
BMI (kg/m2) | 23.8 ± 2.6 | 25.1 ± 2.9 | < 0.001 | 23.8 ± 2.7 | 25.2 ± 3.3 | <0.001 | 23.8 ± 2.7 | 25.2 ± 3.1 | < 0.001 | ||||||
Waist Circumference (cm) | 84.7 ± 7.4 | 88.3 ± 7.7 | < 0.001 | 79.6 ± 7.5 | 83.4 ± 8.4 | <0.001 | 82.1 ± 7.9 | 85.9 ± 8.4 | < 0.001 | ||||||
Total Energy Intake (kcal) | 1749.8 ± 473.2 | 1795.5 ± 473.8 | 0.037 | 1585.9 ± 474.6 | 1629.6 ± 489.6 | 0.053 | 1667.3 ± 480.8 | 1715.5 ± 488.5 | 0.002 | ||||||
Total Carbohydrate Intake (gram) | 314.9 ± 79.3 | 318.3 ± 77.9 | 0.351 | 289.2 ± 84.1 | 297.6 ± 84.6 | 0.033 | 302.0 ± 82.7 | 308.3 ± 81.8 | 0.019 | ||||||
Total Fiber Intake (gram) | 5.8 ± 2.8 | 5.7 ± 2.5 | 0.141 | 5.7 ± 2.8 | 5.7 ± 3.0 | 0.977 | 5.8 ± 2.8 | 5.7 ± 2.8 | 0.337 | ||||||
Total Protein Intake (gram) | 58.9 ± 22.6 | 61.3 ± 22.6 | 0.02 | 53.7 ± 21.8 | 54.6 ± 22.4 | 0.385 | 56.3 ± 22.4 | 58.1 ± 22.8 | 0.015 | ||||||
Total Fat Intake (gram) | 26.1 ± 14.5 | 28.4 ± 15.4 | 0.001 | 22.3 ± 13.2 | 22.7 ± 14.0 | 0.546 | 24.2 ± 14.0 | 25.6 ± 15.0 | 0.002 |
No. | SNP | Minor Allele | MAF | Function | Diabetes | Fasting Blood Glucose | HbA1c | ||||
---|---|---|---|---|---|---|---|---|---|---|---|
(Controls 1484; Cases 2504) | |||||||||||
Cases | Controls | OR (95% CI) | Add p-Value | Beta ± se | Add p-Value | Beta ± se | Add p-Value | ||||
1 | rs7756992 | A | 0.40 | 0.48 | Intron | 0.73 (0.66–0.80) | 3.16 × 10−10 | −1.20 ± 0.17 | 7.93 × 10−13 | −0.04 ± 0.01 | 8.13 × 10−5 |
2 | rs9368222 | A | 0.48 | 0.44 | Intron | 1.35 (1.22–1.49) | 5.40 × 10−9 | 1.25 ± 0.17 | 1.18 × 10−13 | 0.04 ± 0.01 | 2.67 × 10−6 |
3 | rs2206734 | T | 0.48 | 0.44 | Intron | 1.35 (1.22–1.49) | 4.91 × 10−9 | 1.30 ± 0.17 | 8.51 × 10−15 | 0.05 ± 0.01 | 1.61 × 10−7 |
4 | rs9465871 | T | 0.40 | 0.48 | Intron | 0.73 (0.66–0.80) | 5.46 × 10−10 | −1.20 ± 0.17 | 8.09 × 10−13 | −0.03 ± 0.01 | 2.00 × 10−4 |
5 | rs7747752 | G | 0.42 | 0.50 | Intron | 0.74 (0.67–0.81) | 1.45 × 10−9 | −1.23 ± 0.17 | 1.92 × 10−13 | −0.04 ± 0.01 | 9.32 × 10−5 |
6 | rs9356744 | C | 0.48 | 0.44 | Intron | 1.35 (1.22–1.49) | 5.74 × 10−9 | 1.25 ± 0.17 | 9.29 × 10−14 | 0.05 ± 0.01 | 7.89 × 10−7 |
7 | rs6908425 | T | 0.16 | 0.21 | Intron | 0.68 (0.60–0.78) | 8.14 × 10−9 | −0.91 ± 0.22 | 2.16 × 10−5 | −0.01 ± 0.01 | 0.227 |
Men | Women | Total | |||||||
---|---|---|---|---|---|---|---|---|---|
Protein (% Energy) | Protein (% Energy) | Protein (% Energy) | |||||||
Tertile 1 | Tertile 2 | Tertile 3 | Tertile 1 | Tertile 2 | Tertile 3 | Tertile 1 | Tertile 2 | Tertile 3 | |
Median | 11.10 | 13.13 | 15.55 | 10.87 | 12.90 | 15.59 | 10.97 | 13.02 | 15.56 |
Ranges | 7.76–12.15 | 12.15–14.09 | 14.09–30.05 | 7.47–11.86 | 11.87–14.01 | 14.01–29.14 | 7.47–11.99 | 11.99–14.07 | 14.07–30.05 |
rs7756992 | |||||||||
AA | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) |
AG | 1.33 (0.78–2.27) | 1.53 (0.85–2.78) | 0.97 (0.56–1.67) | 1.40 (0.81–2.42) | 0.89 (0.49–1.60) | 2.08 (1.12–3.88) | 1.39 (0.95–2.03) | 1.17 (0.78–1.75) | 1.35 (0.90–2.01) |
GG | 2.04 (1.16–3.60) | 1.91 (1.02–3.58) | 1.01 (0.55–1.87) | 1.88 (1.01–3.50) | 1.17 (0.64–2.14) | 2.29 (1.16–4.53) | 2.05 (1.35–3.09) | 1.43 (0.93–2.20) | 1.47 (0.94–2.30) |
p for trend 1 | 0.034 | 0.674 | 0.937 | 0.278 | 0.475 | 0.011 | 0.001 | 0.113 | 0.842 |
Men | Women | Total | |||||||
---|---|---|---|---|---|---|---|---|---|
Fat (% Energy) | Fat (% Energy) | Fat (% Energy) | |||||||
Tertile 1 | Tertile 2 | Tertile 3 | Tertile 1 | Tertile 2 | Tertile 3 | Tertile 1 | Tertile 2 | Tertile 3 | |
Median | 8.66 | 12.92 | 18.19 | 7.48 | 11.34 | 16.75 | 8.05 | 12.18 | 17.48 |
Ranges | 2.56–11.03 | 11.03–15.16 | 15.17–35.23 | 2.37–9.49 | 9.49–13.67 | 13.67–43.51 | 2.37–10.14 | 10.15–14.39 | 14.40–43.51 |
rs7756992 | |||||||||
AA | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) | 1.00 (reference) |
AG | 1.26 (0.76–2.12) | 1.33 (0.74–2.39) | 1.16 (0.66–2.06) | 1.19 (0.69–2.06) | 1.29 (0.73–2.28) | 1.67 (0.88–3.15) | 1.12 (0.76–1.64) | 1.37 (0.93–2.02) | 1.45 (0.95–2.19) |
GG | 2.33 (1.34–4.05) | 1.64 (0.88–3.06) | 0.99 (0.52–1.87) | 1.24 (0.68–2.25) | 1.86 (1.00–3.44) | 2.26 (1.11–4.59) | 1.63 (1.08–2.45) | 1.58 (1.03–2.41) | 1.67 (1.05–2.66) |
p for trend 1 | 0.009 | 0.129 | 0.603 | 0.576 | 0.089 | 0.191 | 0.009 | 0.044 | 0.672 |
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Choi, W.J.; Jin, H.-S.; Kim, S.-S.; Shin, D. Dietary Protein and Fat Intake Affects Diabetes Risk with CDKAL1 Genetic Variants in Korean Adults. Int. J. Mol. Sci. 2020, 21, 5607. https://doi.org/10.3390/ijms21165607
Choi WJ, Jin H-S, Kim S-S, Shin D. Dietary Protein and Fat Intake Affects Diabetes Risk with CDKAL1 Genetic Variants in Korean Adults. International Journal of Molecular Sciences. 2020; 21(16):5607. https://doi.org/10.3390/ijms21165607
Chicago/Turabian StyleChoi, Woo Jeong, Hyun-Seok Jin, Sung-Soo Kim, and Dayeon Shin. 2020. "Dietary Protein and Fat Intake Affects Diabetes Risk with CDKAL1 Genetic Variants in Korean Adults" International Journal of Molecular Sciences 21, no. 16: 5607. https://doi.org/10.3390/ijms21165607