A Meta-Analysis of Association between Methylenetetrahydrofolate Reductase Gene (MTHFR) 677C/T Polymorphism and Diabetic Retinopathy
Abstract
:1. Introduction
2. Methods
2.1. Identification and Eligibility of Relevant Studies
2.2. Data Extraction and Conversion
2.3. Quality Assessment and Study Stratification
2.4. Meta-Analysis
3. Results
3.1. Literature Search
3.2. Eligible Studies and Study Characteristics
3.3. Summary Statistics
3.4. Main Results, Stratification, and Sensitivity Analyses
3.5. Source of Heterogeneity and Publication Bias
4. Discussion
5. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Author (Ref *) | Year | Ethnicity | Design | Case | Control | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Sample Size | Age (year) | DM Duration (year) | Definition | Sample Size | Age (year) | DM Duration (year) | Definition | HWE # | MAF & | NOS (Stars) | ||||
Neugebauer, S. et al. [12] | 1997 | Japan | CS | 76 | 55.5 ± 7.9 | 16.5 ± 5.1 | DR | 36 | 50.5 ± 9.7 | 11.2 ± 4.2 | NCTDM | 0.67 | 0.26 | 7 |
Fujita, H. et al. [13] | 1999 | Japan | CS | 105 | 60±12 | NR | PDR + DN | 68 | 62 ± 10 | NR | T2DM | 0.14 | 0.42 | 6 |
Lauszus, F.F. et al. [14] | 2001 | Denmark | CS | 112 | NR | NR | DR | 1084 | NR | NR | T1DM | 0.53 | 0.29 | 5 |
Wang, L.Q. et al. [15] | 2001 | China | CC | 62 | 62.50 ± 8.08 | 8.29 ± 6.40 | DR | 202 | 59.42 ± 14.87 for T2DM41.83 ± 17.10 for Healthy | 7.29 ± 5.80 for T2DM | Healthy + T2DM | 0.73 | 0.32 | 8 |
Yang, G.Q. et al. [16] | 2001 | China | CC | 60 | 50.7 ± 12.1 | 1 (0.1–4) | DR | 231 | 51.1 ± 12.8 for T2DM with DN63.0 ± 8.8 for T2DM with NCD52.6 ± 14.9 for Healthy | 2 (1–4) for T2DM with DN14 (11–18) for T2DM with NCD | Healthy + T2DM | 0.73 | 0.44 | 8 |
Maeda, M. et al. [17] | 2003 | Japan | CS | 51 | NR | NR | DR | 105 | NR | NR | T2DM | 0.06 | 0.37 | 5 |
Santos, K.G. et al. [18] | 2003 | Brazil | CS | 99 | NA | NA | DR | 111 | NA | NA | T2DM | 0.98 | 0.39 | 6 |
Sun, J. et al. [19] | 2003 | China | CC | 110 | 55.6 ± 6.7 | <5 | DR | 155 | 54.7 ± 7.1 for NDR42.3 ± 6.1 for Healthy | >10 for NDR | T2DM | 0.00 | 0.33 | 7 |
Yoshioka, K. et al. [20] | 2003 | Japan | CS | 98 | NA | NA | DR | 268 | NA | NA | T2DM | 0.46 | 0.38 | 6 |
Huang, D.F. et al. [21] | 2005 | China | CC | 50 | NR | NR | DR | 47 | NR | NR | Healthy | 0.96 | 0.26 | 5 |
Yi, X.X. et al. [22] | 2005 | China | CC | 249 | 56.53 ± 10.45 | 5.9 ± 4 | DR | 65 | NR | NR | Healthy | 0.01 | 0.31 | 5 |
Errera, F.I. et al. [23] | 2006 | Brazil | CC | 141 | 55.43 ± 15.33 | 18 ± 8.67 | DR | 107 | 66.11 ± 7.06 | NA | Healthy | 0.24 | 0.40 | 6 |
Liu, D.M. et al. [24] | 2006 | China | CC | 44 | 51.9 ± 7.5 | NR | DR | 84 | 54.0 ± 13.2 | NA | Healthy | 0.01 | 0.29 | 5 |
Maeda, M. et al. [25] | 2008 | Japan | CS | 75 | NA | NA | DR | 115 | NA | NA | T2DM | 0.06 | 0.36 | 5 |
Ukinc, K. et al. [26] | 2009 | Turkey/ | CS | 25 | NA | NA | DR | 27 | NA | NA | T2DM | 0.10 | 0.24 | 5 |
Ren, M. et al. [27] | 2011 | China | CC | 161 | 59.95 ± 10.55 | 11 | DR | 213 | 58.52 ± 12.61 | 7 | T2DM | 0.23 | 0.42 | 7 |
Yigit, S. et al. [28] | 2013 | Turkey | CS | 81 | NA | NA | DR | 149 | NA | NA | T1DM + T2DM | 0.98 | 0.24 | 5 |
Simoes, M.J. et al. [29] | 2014 | Portugal | CS | 148 | 58.5 ± 8.4 | 10.5 ± 5.3 | PDR | 79 | 61.8 ± 7.8 | 8.9 ± 4.8 | T2DM | 0.73 | 0.24 | 7 |
Author (Ref) | Prevalence of MTHFR C677T Genotype | Prevalence of Allele Frequency | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
CC | CT | TT | C | T | ||||||
Case | Control | Case | Control | Case | Control | Case | Control | Case | Control | |
Neugebauer, S. et al. [12] | 26 | 20 | 38 | 13 | 12 | 3 | 90 | 53 | 62 | 19 |
Fujita, H. et al. [13] | 31 | 20 | 57 | 39 | 17 | 9 | 119 | 79 | 91 | 57 |
Lauszus, F.F. et al. [14] | 47 | 542 | 57 | 455 | 8 | 87 | 151 | 1539 | 73 | 629 |
Wang, L.Q. et al. [15] | 8 | 94 | 27 | 86 | 27 | 22 | 43 | 274 | 81 | 130 |
Yang, G.Q. et al. [16] | 8 | 75 | 33 | 111 | 19 | 45 | 49 | 261 | 71 | 201 |
Maeda, M. et al. [17] | 18 | 37 | 20 | 58 | 13 | 10 | 56 | 132 | 46 | 78 |
Santos, K.G. et al. [18] | 34 | 41 | 53 | 53 | 12 | 17 | 121 | 135 | 77 | 87 |
Sun, J. et al. [19] | 33 | 82 | 46 | 45 | 31 | 28 | 112 | 209 | 108 | 101 |
Yoshioka, K. et al. [20] | 33 | 100 | 50 | 132 | 15 | 36 | 116 | 332 | 80 | 204 |
Huang, D.F. et al. [21] | 17 | 26 | 25 | 18 | 8 | 3 | 59 | 70 | 41 | 24 |
Yi, X.X. et al. [22] | 68 | 35 | 110 | 19 | 71 | 11 | 246 | 89 | 252 | 41 |
Errera, F.I. et al. [23] | 61 | 36 | 66 | 57 | 14 | 14 | 188 | 129 | 94 | 85 |
Liu, D.M. et al. [24] | 18 | 47 | 16 | 25 | 10 | 12 | 52 | 119 | 36 | 49 |
Maeda, M. et al. [25] | 31 | 43 | 28 | 62 | 16 | 10 | 90 | 148 | 60 | 82 |
Ukinc, K. et al. [26] | 14 | 14 | 11 | 13 | 0 | 0 | 39 | 41 | 11 | 13 |
Ren, M. et al. [27] | 26 | 77 | 78 | 95 | 57 | 41 | 130 | 249 | 192 | 177 |
Yigit, S. et al. [28] | 38 | 85 | 30 | 55 | 13 | 9 | 106 | 225 | 56 | 73 |
Simoes, M.J. et al. [29] | 69 | 45 | 60 | 30 | 19 | 4 | 198 | 120 | 98 | 38 |
Total | 580 | 1419 | 805 | 1366 | 362 | 361 | 1965 | 4204 | 1529 | 2088 |
Subgroup | Genetic Model | Studies No (All/Sensitivity) | OR (95% CI) | p * | I2 (%) | OR se (95% CI) # |
---|---|---|---|---|---|---|
Overall | CT vs. CC | 18/15 | 1.46 (1.15–1.86) | 0.00 | 60.0 | 1.32 (1.02–1.70) |
TT vs. CC | 18/15 | 2.45 (1.66–3.60) | 0.00 | 69.0 | 2.27 (1.44–3.58) | |
Allele contrast | 18/15 | 1.52 (1.26–1.84) | 0.00 | 72.4 | 1.45 (1.17–1.79) | |
Recessive model | 18/15 | 1.67 (1.19–2.40) | 0.00 | 71.9 | 1.87 (1.32–2.66) | |
Dominant model | 18/15 | 1.71 (1.28–2.28) | 0.00 | 75.3 | 1.50 (1.13–1.98) | |
Asian | CT vs. CC | 12/9 | 1.71 (1.22–2.39) | 0.00 | 64.9 | 1.52 (1.01–2.30) |
TT vs. CC | 12/9 | 2.97 (2.06–4.29) | 0.02 | 51.5 | 3.07 (1.83–5.14) | |
Allele contrast | 12/9 | 1.75 (1.42–2.18) | 0.00 | 67.3 | 1.69 (1.28–2.24) | |
Recessive model | 12/9 | 2.16 (1.75–2.65) | 0.11 | 35.1 | 2.34(1.62–3.38) | |
Dominant model | 12/9 | 1.98 (1.42–2.76) | 0.00 | 68.6 | 1.83 (1.20–2.81) | |
Non-Asian | CT vs. CC | 6/6 | 1.15 (0.92–1.45) | 0.38 | 5.4 | 1.15 (0.92–1.45) |
TT vs. CC | 6/6 | 1.33 (0.69–2.54) | 0.04 | 61.4 | 1.33 (0.69–2.54) | |
Allele contrast | 6/6 | 1.14 (0.89–1.46) | 0.07 | 51.5 | 1.14 (0.89–1.46) | |
Recessive model | 6/6 | 1.24 (0.69–2.23) | 0.05 | 57.7 | 1.24 (0.69–2.23) | |
Dominant model | 6/6 | 1.18 (0.95–1.47) | 0.21 | 30.70 | 1.18 (0.95–1.47) | |
T2DM | CT vs. CC | 12/10 | 1.50 (1.08–2.09) | 0.00 | 66.5 | 1.32 (0.93–1.86) |
TT vs. CC | 12/10 | 2.68 (1.74–4.13) | 0.00 | 66.2 | 2.61 (1.50–4.53) | |
Allele contrast | 12/10 | 1.59 (1.26–2.01) | 0.00 | 74.0 | 1.49 (1.14–1.96) | |
Recessive model | 12/10 | 2.05 (1.47–2.84) | 0.01 | 56.9 | 2.10 (1.38–3.17) | |
Dominant model | 12/10 | 1.72 (1.23–2.42) | 0.00 | 72.1 | 1.54 (1.06–2.24) | |
Non-T2DM | CT vs. CC | 6/5 | 1.30 (1.02–1.66) | 0.12 | 43.5 | 1.32 (0.89–1.97) |
TT vs. CC | 6/5 | 1.75 (0.93–3.27) | 0.05 | 55.9 | 1.70 (0.80–3.63) | |
Allele contrast | 6/5 | 1.38 (1.02–1.88) | 0.02 | 64.5 | 1.34 (0.95–1.91) | |
Recessive model | 6/5 | 1.38 (0.96–2.00) | 0.14 | 39.5 | 1.32 (0.89–1.97) | |
Dominant model | 6/5 | 1.46 (1.00–2.13) | 0.04 | 57.4 | 1.42 (0.92–2.19) | |
Asian with T2DM | CT vs. CC | 9/7 | 1.64 (1.07–2.50) | 0.00 | 73.8 | 1.40 (0.86–2.29) |
TT vs. CC | 9/7 | 3.00 (1.92–4.68) | 0.01 | 63.8 | 2.99 (1.63–5.50) | |
Allele contrast | 9/7 | 1.73 (1.33–2.26) | 0.00 | 76.0 | 1.64 (1.17–2.29) | |
Recessive model | 9/7 | 2.21 (1.59–3.06) | 0.03 | 51.9 | 2.33 (1.52–3.57) | |
Dominant model | 9/7 | 1.94 (1.27–2.94) | 0.00 | 76.7 | 1.72 (1.03–2.89) | |
Asian with Non-T2DM | CT vs. CC | 3/2 | 1.99 (1.22–3.25) | 0.87 | 0.0 | 2.19 (1.19–4.01) |
TT vs. CC | 3/2 | 2.80 (1.39–5.66) | 0.77 | 0.0 | 3.50 (1.28–9.62) | |
Allele contrast | 3/2 | 1.86 (1.32–2.60) | 0.90 | 0.0 | 1.97 (1.28–3.05) | |
Recessive model | 3/2 | 2.06 (1.06–4.02) | 0.87 | 0.0 | 2.38 (0.91–6.24) | |
Dominant model | 3/2 | 2.17 (1.38–3.42) | 0.85 | 0.0 | 2.40 (1.35–4.28) | |
Non-Asian with T2DM | CT vs. CC | 3/3 | 1.20 (0.81–1.76) | 0.79 | 0.0 | 1.20 (0.81–1.76) |
TT vs. CC | 3/3 | 1.54 (0.43–5.46) | 0.08 | 68.2 | 1.54 (0.43–5.46) | |
Allele contrast | 3/3 | 1.18 (0.90–1.56) | 0.25 | 27.0 | 1.18 (0.90–1.56) | |
Recessive model | 3/3 | 1.37 (0.39–4.82) | 0.06 | 70.8 | 1.37 (0.39–4.82) | |
Dominant model | 3/3 | 1.24 (0.86–1.80) | 0.58 | 0.0 | 1.24 (0.86–1.80) | |
Non-Asian with Non-T2DM | CT vs. CC | 3/3 | 1.09 (0.69–1.71) | 0.09 | 58.0 | 1.09 (0.69–1.71) |
TT vs. CC | 3/3 | 1.24 (0.49–3.14) | 0.03 | 71.9 | 1.24 (0.49–3.14) | |
Allele contrast | 3/3 | 1.13 (0.76–1.68) | 0.02 | 73.3 | 1.13 (0.76–1.68) | |
Recessive model | 3/3 | 1.21 (0.54–2.72) | 0.05 | 66.9 | 1.21 (0.54–2.72) | |
Dominant model | 3/3 | 1.13 (0.69–1.83) | 0.05 | 66.7 | 1.13 (0.69–1.83) |
Subgroup | Egger Test | Begg Test | ||
---|---|---|---|---|
Dominant | Recessive | Dominant | Recessive | |
all study | 0.59 | 0.48 | 0.65 | 0.48 |
T2DM | 0.91 | 0.94 | 0.84 | 0.64 |
Non-T2DM | 0.28 | 0.16 | 0.06 | 0.26 |
Asian | 0.62 | 0.91 | 0.63 | 0.54 |
Non-Asian | 0.57 | 0.10 | 1.00 | 0.46 |
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Luo, S.; Wang, F.; Shi, C.; Wu, Z. A Meta-Analysis of Association between Methylenetetrahydrofolate Reductase Gene (MTHFR) 677C/T Polymorphism and Diabetic Retinopathy. Int. J. Environ. Res. Public Health 2016, 13, 806. https://doi.org/10.3390/ijerph13080806
Luo S, Wang F, Shi C, Wu Z. A Meta-Analysis of Association between Methylenetetrahydrofolate Reductase Gene (MTHFR) 677C/T Polymorphism and Diabetic Retinopathy. International Journal of Environmental Research and Public Health. 2016; 13(8):806. https://doi.org/10.3390/ijerph13080806
Chicago/Turabian StyleLuo, Shasha, Furu Wang, Chao Shi, and Zhifeng Wu. 2016. "A Meta-Analysis of Association between Methylenetetrahydrofolate Reductase Gene (MTHFR) 677C/T Polymorphism and Diabetic Retinopathy" International Journal of Environmental Research and Public Health 13, no. 8: 806. https://doi.org/10.3390/ijerph13080806