Are MTHFR C677T and MTRR A66G Polymorphisms Associated with Overweight/Obesity Risk? From a Case-Control to a Meta-Analysis of 30,327 Subjects
Abstract
:1. Introduction
2. Results
2.1. Population Characteristics in Our Case-Control Study
2.2. Genotype Distribution and Association Analysis in Our Case-Control Study
Characteristics | Controls | Overweight/Obesity | p-Value |
---|---|---|---|
Number of subjects | 741 | 517 | - |
Gender (male/female) | 369/372 | 261/256 | 0.819 |
Age (year) | 44.57 ± 9.71 | 47.4 ± 9.72 | <0.001 |
Height (cm) | 166.81 ± 7.41 | 166.74 ± 8.23 | 0.877 |
Weight (kg) | 61.14 ± 6.94 | 75.31 ± 10.34 | <0.001 |
BMI (kg/m2) | 21.92 ± 1.39 | 27.02 ± 2.56 | <0.001 |
WC (cm) | 78.16 ± 6.67 | 90.22 ± 8.32 | <0.001 |
SBP (mmHg) | 122.36 ± 17.17 | 133.89 ± 19.08 | <0.001 |
DBP (mmHg) | 77.25 ± 10.77 | 84.33 ± 12.63 | <0.001 |
FBG (mmol/L) | 5.03 ± 0.70 | 5.27 ± 0.88 | <0.001 |
TC (mmol/L) | 4.85 ± 1.02 | 5.05 ± 0.99 | 0.001 |
TG (mmol/L) | 1.01 ± 1.00 | 1.56 ± 0.98 | <0.001 |
HDL-C (mmol/L) | 1.31 ± 0.35 | 1.19 ± 0.30 | <0.001 |
LDL-C (mmol/L) | 2.67 ± 0.93 | 2.80 ± 0.94 | 0.016 |
Polymorphism | Cases (n = 517) | Controls (n = 741) | Crude OR (95% CI) | p-Value | Adjusted OR a | p-Value |
---|---|---|---|---|---|---|
MTHFR C677T | ||||||
CC | 115 (22.2) | 160 (21.6) | 1.00 | - | 1.00 | - |
CT | 244 (47.2) | 375 (50.6) | 0.91 (0.68–1.21) | 0.499 | 0.83 (0.59–1.18) | 0.308 |
TT | 158 (30.6) | 206 (27.8) | 1.07 (0.78–1.47) | 0.688 | 1.06 (0.75–1.51) | 0.738 |
Allelic model | - | - | 1.04 (0.89–1.22) | 0.602 | 1.05 (0.85–1.30) | 0.626 |
Dominant model | - | - | 0.96 (0.73–1.26) | 0.783 | 0.92 (0.65–1.32) | 0.655 |
Recessive model | - | - | 1.14 (0.89–1.46) | 0.288 | 1.21 (0.88–1.67) | 0.245 |
MTRR A66G | ||||||
AA | 298 (57.6) | 437 (59.0) | 1.00 | - | 1.00 | - |
AG | 186 (36.0) | 251 (33.9) | 1.09 (0.86–1.38) | 0.497 | 1.15 (0.92–1.43) | 0.216 |
GG | 33 (6.4) | 53 (7.1) | 0.91 (0.58–1.45) | 0.698 | 0.82 (0.53–1.25) | 0.344 |
Allelic model | - | - | 1.02 (0.84–1.22) | 0.871 | 1.11 (0.87–1.41) | 0.403 |
Dominant model | - | - | 1.06 (0.84–1.33) | 0.637 | 1.17 (0.87–1.58) | 0.291 |
Recessive model | - | - | 0.89 (0.56–1.39) | 0.595 | 0.99 (0.56–1.76) | 0.968 |
2.3. Meta-Analysis Results
Study | Genotype Distribution | Allele Frequency | HWE Test | Number of Cases/Controls | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
First Author (Year) | Cases | Controls | Cases | Controls | χ2 | p | |||||||
MTHFR C677T | CC | CT | TT | CC | CT | TT | C | T | C | T | - | - | - |
Thawnashom et al. (2005) [4] | 67 | - | 23 e | 34 | - | 16 e | NA | NA | NA | NA | NA | NA | 90/50 |
Terruzzi et al. (2007) [5] | 18 | 54 | 12 | 14 | 33 | 5 | 90 | 78 | 61 | 43 | 4.9466 | 0.026 | 84/52 |
Lewis et al. (2008) [6] a | 360 | 410 | 112 | 1165 | 1086 | 283 | 1130 | 634 | 3416 | 1652 | 1.5459 | 0.214 | 882/2534 |
Lewis et al. (2008) [6] b | 163 | 155 | 38 | 2707 | 2713 | 715 | 481 | 231 | 8127 | 4143 | 0.7882 | 0.375 | 356/6135 |
Lewis et al. (2008) [6] c | 115 | 93 | 25 | 2155 | 2190 | 552 | 323 | 143 | 6500 | 3294 | 0.0153 | 0.902 | 233/4897 |
Lewis et al. (2008) [6] d | 588 | 574 | 107 | 3812 | 3356 | 736 | 1750 | 788 | 10,980 | 4828 | 0.0045 | 0.946 | 1269/7904 |
Settin et al. (2009) [7] | 89 | 34 | 5 | 69 | 36 | 5 | 212 | 44 | 174 | 46 | 0.0121 | 0.912 | 128/110 |
Bazzaz et al. (2010) [8] | 44 | 21 | 9 | 113 | 80 | 14 | 109 | 39 | 306 | 108 | 0.0009 | 0.975 | 74/207 |
Gara et al. (2011) [9] | 15 | 14 | 2 | 9 | 12 | 1 | 44 | 18 | 30 | 14 | 1.4550 | 0.228 | 31/22 |
Chauhan et al. (2012) [10] | 348 | 185 | 29 | 272 | 148 | 16 | 881 | 243 | 692 | 180 | 0.5680 | 0.451 | 562/436 |
Yin et al. (2012) [11] | 354 | 341 | 56 | 471 | 441 | 66 | 1049 | 453 | 1383 | 573 | 7.6608 | 0.006 | 751/978 |
Tabassum et al. (2012) [12] | 290 | 144 | 20 | 581 | 218 | 31 | 724 | 184 | 1380 | 280 | 0.8313 | 0.068 | 454/830 |
Our study | 115 | 244 | 158 | 160 | 375 | 206 | 474 | 560 | 695 | 787 | 0.1911 | 0.662 | 517/741 |
MTRR A66G | AA | AG | GG | AA | AG | GG | A | G | A | G | - | - | - |
Terruzzi et al. (2007) [5] | 39 | 42 | 0 | 36 | 16 | 1 | 120 | 42 | 88 | 18 | 0.2649 | 0.607 | 81/53 |
Tabassum et al. (2012) [12] | 110 | 231 | 106 | 244 | 407 | 169 | 451 | 443 | 895 | 745 | 0.0009 | 0.976 | 447/820 |
Our study | 298 | 186 | 33 | 437 | 251 | 53 | 782 | 252 | 1125 | 357 | 4.0366 | 0.045 | 517/741 |
Subgroup | Recessive | Dominant | Homozygous Codominant | Heterozygous Codominant | Allelic Model | |||||
---|---|---|---|---|---|---|---|---|---|---|
OR (95% CI) | Ph | OR (95% CI) | Ph | OR (95% CI) | Ph | OR (95% CI) | Ph | OR (95% CI) | Ph | |
MTHFR C677T polymorphism | ||||||||||
Overall | 1.05 (0.94–1.16) | 0.730 | 1.05 (0.99–1.13) | 0.140 | 1.06 (0.94–1.18) | 0.664 | 1.06 (0.99–1.13) | 0.095 | 1.05 (1.00–1.10) | 0.284 |
Ethnicity | ||||||||||
Asian | 1.18 (0.99–1.41) | 0.862 | 1.04 (0.93–1.16) | 0.304 | 1.16 (0.95–1.42) | 0.880 | 1.02 (0.91–1.15) | 0.155 | 1.07 (0.98–1.16) | 0.513 |
Caucasian | 0.99 (0.86–1.13) | 0.477 | 1.04 (0.90–1.20) | 0.049 | 1.02 (0.89–1.18) | 0.209 | 1.05 (0.91–1.21) | 0.080 | 1.02 (0.92-1.13) | 0.077 |
African | 1.45 (0.12–17.04) | - | 0.74 (0.25–2.23) | - | 1.20 (0.10–15.20) | - | 0.70 (0.23–2.17) | - | 0.88 (0.38–2.03) | - |
Source of control | ||||||||||
Population based | 1.02 (0.90–1.45) | 0.581 | 1.07 (1.00–1.18) | 0.057 | 1.05 (0.93–1.20) | 0.356 | 1.07 (0.96–1.19) | 0.076 | 1.05 (0.97–1.13) | 0.088 |
Hospital based | 1.19 (0.95–1.49) | 0.786 | 0.90 (0.74–1.10) | 0.810 | 1.13 (0.85–1.50) | 0.782 | 0.85 (0.68–1.06) | 0.722 | 1.02 (0.89–1.17) | 0.736 |
Genotyping method | ||||||||||
PCR-RFLP | 0.98 (0.82–1.17) | 0.261 | 1.01 (0.85–1.20) | 0.596 | 1.02 (0.85–1.23) | 0.434 | 1.07 (0.97–1.19) | 0.397 | 1.03 (0.96–1.11) | 0.911 |
TaqMan | 1.07 (0.93–1.24) | 0.729 | 0.96 (0.80–1.16) | 0.026 | 1.07 (0.91–1.25) | 0.356 | 0.95 (0.79–1.15) | 0.040 | 1.00 (0.88–1.13) | 0.054 |
Others | 1.30 (0.86–1.97) | 0.909 | 1.10 (1.00–1.23) | 0.377 | 1.35 (0.88–2.05) | 0.974 | 1.13 (0.94–1.36) | 0.191 | 1.15 (0.99–1.33) | 0.450 |
Sample size | ||||||||||
Large study | 1.04 (0.93–1.16) | 0.615 | 1.06 (0.96–1.16) | 0.075 | 1.06 (0.94–1.19) | 0.468 | 1.05 (0.95–1.16) | 0.077 | 1.05 (1.00–1.10) | 0.138 |
Small study | 1.48 (0.82–2.67) | 0.788 | 0.83 (0.61–1.12) | 0.782 | 1.39 (0.75–2.59) | 0.762 | 0.78 (0.55–1.11) | 0.642 | 0.98 (0.76–1.25) | 0.616 |
MTRR A66G polymorphism | ||||||||||
Overall | 1.09 (0.86–1.38) | 0.476 | 1.27 (0.95–1.70) | 0.106 | 1.19 (0.91–1.55) | 0.246 | 1.28 (0.96–1.72) | 0.116 | 1.14 (0.95–1.35) | 0.194 |
3. Discussion
4. Experimental Section
4.1. Study Subjects
4.2. Clinical Measurements and Laboratory Tests
4.3. Genotyping Analysis
4.4. Statistical Analysis
4.5. Meta-Analysis
5. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Fan, S.-J.; Yang, B.-Y.; Zhi, X.-Y.; He, M.; Wang, D.; Wang, Y.-X.; Wang, Y.-N.; Wei, J.; Zheng, Q.-M.; Sun, G.-F. Are MTHFR C677T and MTRR A66G Polymorphisms Associated with Overweight/Obesity Risk? From a Case-Control to a Meta-Analysis of 30,327 Subjects. Int. J. Mol. Sci. 2015, 16, 11849-11863. https://doi.org/10.3390/ijms160611849
Fan S-J, Yang B-Y, Zhi X-Y, He M, Wang D, Wang Y-X, Wang Y-N, Wei J, Zheng Q-M, Sun G-F. Are MTHFR C677T and MTRR A66G Polymorphisms Associated with Overweight/Obesity Risk? From a Case-Control to a Meta-Analysis of 30,327 Subjects. International Journal of Molecular Sciences. 2015; 16(6):11849-11863. https://doi.org/10.3390/ijms160611849
Chicago/Turabian StyleFan, Shu-Jun, Bo-Yi Yang, Xue-Yuan Zhi, Miao He, Da Wang, Yan-Xun Wang, Yi-Nuo Wang, Jian Wei, Quan-Mei Zheng, and Gui-Fan Sun. 2015. "Are MTHFR C677T and MTRR A66G Polymorphisms Associated with Overweight/Obesity Risk? From a Case-Control to a Meta-Analysis of 30,327 Subjects" International Journal of Molecular Sciences 16, no. 6: 11849-11863. https://doi.org/10.3390/ijms160611849
APA StyleFan, S. -J., Yang, B. -Y., Zhi, X. -Y., He, M., Wang, D., Wang, Y. -X., Wang, Y. -N., Wei, J., Zheng, Q. -M., & Sun, G. -F. (2015). Are MTHFR C677T and MTRR A66G Polymorphisms Associated with Overweight/Obesity Risk? From a Case-Control to a Meta-Analysis of 30,327 Subjects. International Journal of Molecular Sciences, 16(6), 11849-11863. https://doi.org/10.3390/ijms160611849