Opposite Genetic Effects of CMIP Polymorphisms on the Risk of Type 2 Diabetes and Obesity: A Family-Based Study in China
Abstract
:1. Introduction
2. Results
3. Discussion
4. Materials and Methods
4.1. Study Population
4.2. Ascertainment of T2DM Status, Including T2DM, Prediabetes, and Normal Glucose Levels
4.3. Measurement and Calculation of Obesity-Related Phenotypes
4.4. Genotyping
4.5. Assessment of Covariates
4.6. Statistical Analysis
5. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
Abbreviations
CMIP | C-maf-Inducing Protein |
T2DM | Type 2 diabetes mellitus |
BMI | Body mass index |
WC | Waist circumference |
HC | Hip circumference |
PBF | Percentage of body fat |
GWAS | Genome-wide association study |
NF-κB | Nuclear factor-κB |
Th2 | T-helper 2 |
SNP | Single nucleotide polymorphism |
WHR | Waist-to-hip ratio |
WHRadjBMI | Waist-to-hip ratio adjusted for body mass index |
OR | Odds ratio |
95% CI | 95% confidence interval |
SD | Standard deviation |
SE | Standard error |
CDKN2A/2B | Cyclin-Dependent Kinase Inhibitor 2A/2B |
KCNJ11 | Potassium Voltage-Gated Channel Subfamily J Member 11 |
TCF7L2 | Transcription Factor 7 Like 2 |
ELMO1 | Engulfment and Cell Motility 1 |
BCL11A | B Cell CLL/Lymphoma 11A |
DHEAS | Dihydroepiandrosterone sulphate |
ARL15 | ADP Ribosylation Factor Like GTPase 15 |
QPCTL | Glutaminyl-Peptide Cyclotransferase-Like |
CPEB4 | Cytoplasmic Polyadenylation Element Binding Protein 4 |
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Characteristics | Normal | Prediabetes | T2DM | p-Value |
---|---|---|---|---|
(n = 899) | (n = 963) | (n = 1582) | ||
Age (years), mean (SD) | 57.5 ± 8.2 | 59.4 ± 7.8 | 59.3 ± 7.5 | 4.04 × 10−8 |
Male, % | 56.8 | 52.2 | 42.2 | 8.01 × 10−13 |
Hypertension, % | 53.3 | 59.8 | 61.7 | 1.88 × 10−4 |
Hyperlipidemia, % | 25.1 | 32.1 | 45.0 | <2.20 × 10−16 |
Smoking status | 5.00 × 10−5 | |||
Never smoker, % | 50.3 | 51.6 | 58.4 | |
Past smoker, % | 17.9 | 16.6 | 15.3 | |
Current smoker, % | 31.8 | 31.9 | 26.3 | |
Alcohol drinking | 3.90 × 10−16 | |||
Never drinker, % | 53.4 | 53.8 | 66.9 | |
Past drinker, % | 11.4 | 16.2 | 8.7 | |
Current drinker, % | 35.2 | 30.0 | 24.4 | |
Rs2925979, % | 0.261 | |||
TT genotype | 14.8 | 14.8 | 17.2 | |
TC genotype | 49.3 | 48.9 | 49.6 | |
CC genotype | 36.0 | 36.2 | 33.1 |
Phenotype | Total | Male | Female | ||||||
---|---|---|---|---|---|---|---|---|---|
(n = 1862) | (n = 1014) | (n = 848) | |||||||
Normal (n = 899) | Prediabetes (n = 963) | p-Value | Normal (n = 511) | Prediabetes (n = 503) | p-Value | Normal (n = 388) | Prediabetes (n = 460) | p-Value | |
BMI (kg/m2) | 25.4 (3.4) | 26.2 (3.5) | 7.10 × 10−7 * | 25.1 (3.2) | 25.6 (3.3) | 6.63 × 10−4 * | 25.9 (3.5) | 26.8 (3.7) | 5.48 × 10−4 * |
WC (cm) | 89.5 (9.5) | 91.4 (9.3) | 2.30 × 10−5 * | 90.2 (9.3) | 91.8 (9.4) | 8.45 × 10−4 * | 88.6 (9.6) | 90.9 (9.1) | 0.015 |
HC (cm) | 99.4 (7.5) | 100.4 (7.5) | 8.12 × 10−4 * | 98.9 (6.8) | 99.7 (7.0) | 0.005 * | 100.0 (8.3) | 101.2 (7.9) | 0.060 |
WHR | 0.90 (0.06) | 0.91 (0.05) | 0.009 | 0.91 (0.05) | 0.92 (0.05) | 0.025 | 0.89 (0.06) | 0.90 (0.05) | 0.220 |
WHRadjBMI | −0.20 (1.01) | −0.15 (0.98) | 0.472 | −0.18 (1.00) | −0.14 (1.01) | 0.618 | −0.23 (1.03) | −0.17 (0.95) | 0.656 |
PBF (%) | 26.7 (9.2) | 28.8 (9.6) | 1.01 × 10−6 * | 20.5 (5.5) | 21.5 (5.6) | 0.003 * | 34.5 (6.6) | 36.5 (6.5) | 1.57 × 10−4 * |
PBF of arms (%) | 22.9 (10.1) | 25.0 (10.8) | 2.33 × 10−6 * | 15.7 (4.3) | 16.2 (4.2) | 0.012 | 32.1 (7.7) | 34.3 (7.5) | 1.31 × 10−4 * |
PBF of legs (%) | 27.5 (8.9) | 29.3 (9.2) | 7.48 × 10−7 * | 20.6 (4.2) | 21.4 (4.4) | 5.44 × 10−4 * | 36.3 (4.7) | 37.5 (4.6) | 3.53 × 10−4 * |
PBF of trunk (%) | 26.7 (9.8) | 29.2 (10.1) | 7.39 × 10−7 * | 21.2 (7.1) | 22.6 (7.3) | 0.002 * | 33.7 (8.1) | 36.2 (7.7) | 1.01 × 10−4 * |
Total | Male | Female | p-Value for Sex Interaction | ||||
---|---|---|---|---|---|---|---|
(n = 3444) | (n = 1681) | (n = 1763) | |||||
OR (95%CI) | p-Value | OR (95%CI) | p-Value | OR (95%CI) | p-Value | ||
Model 1 | 1.15 (1.02~1.30) | 0.022 | 0.96 (0.79~1.17) | 0.705 | 1.29 (1.11~1.50) | 9.30 × 10−4 | 0.021 |
Model 2 | 1.17 (1.03~1.32) | 0.014 | 0.98 (0.80~1.20) | 0.809 | 1.34 (1.14~1.58) | 4.70 × 10−4 | 0.013 |
Phenotype | Total | Male | Female | p-Value for Sex Interaction | |||
---|---|---|---|---|---|---|---|
(n = 1862) | (n = 1014) | (n = 848) | |||||
β (SE) | p-Value | β (SE) | p-Value | β (SE) | p-Value | ||
BMI | −0.079 (0.034) | 0.019 | −0.015 (0.044) | 0.734 | −0.161 (0.052) | 0.002 * | 0.037 |
WC | −0.055 (0.035) | 0.111 | −0.005 (0.045) | 0.914 | −0.136 (0.052) | 0.010 | 0.083 |
HC | −0.073 (0.035) | 0.040 | −0.000 (0.046) | 0.995 | −0.175 (0.054) | 0.001 * | 0.016 |
WHR | −0.017 (0.036) | 0.623 | −0.011 (0.047) | 0.820 | −0.030 (0.053) | 0.571 | 0.963 |
WHRadjBMI | 0.034 (0.036) | 0.354 | 0.015 (0.049) | 0.765 | 0.050 (0.055) | 0.357 | 0.626 |
PBF | −0.067 (0.035) | 0.056 | −0.002 (0.046) | 0.974 | −0.149 (0.052) | 0.004 * | 0.035 |
PBF of arms | −0.045 (0.035) | 0.202 | 0.023 (0.046) | 0.622 | −0.130 (0.053) | 0.014 | 0.027 |
PBF of legs | −0.073 (0.035) | 0.039 | −0.010 (0.047) | 0.827 | −0.152 (0.053) | 0.004 * | 0.040 |
PBF of trunk | −0.077 (0.035) | 0.029 | −0.016 (0.046) | 0.730 | −0.153 (0.053) | 0.004 * | 0.054 |
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Cao, Y.; Wang, T.; Wu, Y.; Juan, J.; Qin, X.; Tang, X.; Wu, T.; Hu, Y. Opposite Genetic Effects of CMIP Polymorphisms on the Risk of Type 2 Diabetes and Obesity: A Family-Based Study in China. Int. J. Mol. Sci. 2018, 19, 1011. https://doi.org/10.3390/ijms19041011
Cao Y, Wang T, Wu Y, Juan J, Qin X, Tang X, Wu T, Hu Y. Opposite Genetic Effects of CMIP Polymorphisms on the Risk of Type 2 Diabetes and Obesity: A Family-Based Study in China. International Journal of Molecular Sciences. 2018; 19(4):1011. https://doi.org/10.3390/ijms19041011
Chicago/Turabian StyleCao, Yaying, Tao Wang, Yiqun Wu, Juan Juan, Xueying Qin, Xun Tang, Tao Wu, and Yonghua Hu. 2018. "Opposite Genetic Effects of CMIP Polymorphisms on the Risk of Type 2 Diabetes and Obesity: A Family-Based Study in China" International Journal of Molecular Sciences 19, no. 4: 1011. https://doi.org/10.3390/ijms19041011