A Meta-Prediction of Methylenetetrahydrofolate-Reductase Polymorphisms and Air Pollution Increased the Risk of Ischemic Heart Diseases Worldwide
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Selection and Data Extraction
2.2. Quality Assessment
2.3. Data Synthesis and Analysis
3. Results
3.1. Sample Characteristics and Genotype Frequency
3.2. Pooled Meta-Analysis
3.3. Subgroup Analysis by Ethnicity and Countries
3.4. Subgroup Analysis by IHD Subtypes
3.5. Heterogeneous Findings by GIS Map
3.6. Meta-Prediction: MTHFR Polymorphisms and Air Pollution Associated with Risk of IHD
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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MTHFR 677 | IHD | CAD | MI |
---|---|---|---|
(n Case/n Control) | (n Case/n Control) | (n Case/n Control) | |
123 Studies (29,697/31,028) | 93 Studies (22,994/20,221) | 30 Studies (6709/10,807) | |
Overall | Risk Type: TT, CT | Risk Type: TT, CT | |
Protective: CC | Protective: CC | Protective: CC | |
Subgroups | |||
Caucasian | 60 Studies | 47 Studies | 13 Studies |
(22,042/14,925) | (13,817/10,702) | (2850/4223) | |
Risk trend: TT | Risk Type: TT | NS | |
Protective trend: CC | Protective: CC | ||
East Asian | 32 Studies | 25 Studies | 7 Studies |
(7112/9471) | (4855/4931) | (2257/4540) | |
Risk Type: TT | Risk Type: TT | Risk Type: TT | |
Protective: CC | Protective: CC | ||
South Asian | 13 Studies | 8 Studies | 5 Studies |
(2475/2763) | (1447/1621) | (1028/1142) | |
Risk Type: TT, CT | Risk Type: TT, CT | NS | |
Protective: CC | Protective: CC | ||
Mixed group | 3 Studies | 2 Studies | 1 Study |
(951/852) | (882/514) | (69/338) | |
NS | NS | -- | |
Middle Eastern | 7 Studies | 6 Studies | 1 Study |
(1265/1723) | (1169/1623) | (99/100) | |
Risk Type: TT, CT | Risk Type: TT, CT | -- | |
Protective: CC | Protective: CC | ||
Hispanic | 2 Studies | -- | 2 Studies |
(353/364) | (353/364) | ||
NS | NS | ||
African | 6 Studies | 5 Studies | 1 Study |
(874/930) | (824/648) | (50/282) | |
Risk Type: TT | Risk Type: TT, CT | -- |
Genotype per Ethnicity (n Studies) | IHD Cases (n = 29,697) n (%) | Controls (n = 31,028) n (%) | Test of Heterogeneity | Test of Association | |||||
---|---|---|---|---|---|---|---|---|---|
Q | p * | I2 | Risk Ratio (95% CI) | p | |||||
TT (123) | 3812 | (12.84) | 3330 | (10.73) | 238.56 | <0.0001 | 48.9% | 1.23 [1.14, 1.33] | <0.0001 |
Caucasian (60) | 1850 | (11.10) | 1479 | (9.91) | 59.38 | 0.4615 | 0.6% | 1.07 [1.00, 1.14] | 0.0528 |
East Asian (32) | 1439 | (20.23) | 1443 | (15.24) | 60.75 | 0.0011 | 49% | 1.31 [1.17, 1.47] | <0.0001 |
South Asian (13) | 93 | (3.76) | 71 | (2.57) | 20.19 | 0.0635 | 40.6% | 1.51 [1.13, 2.01] | 0.0048 |
Mixed Group (3) | 93 | (9.78) | 88 | (10.33) | 0.05 | 0.9771 | 0% | 0.86 [0.63, 1.17] | 0.33 |
Middle Eastern (7) | 130 | (10.28) | 89 | (5.17) | 27.38 | 0.0001 | 78.1% | 2.62 [1.37, 5.01] | 0.0034 |
Hispanic (2) | 102 | (28.90) | 106 | (29.12) | 1.50 | 0.2204 | 33.4% | 0.99 [0.79, 1.25] | 0.94 |
African (6) | 105 | (12.01) | 54 | (5.81) | 2.03 | 0.8454 | 0% | 2.14 [1.56, 2.94] | <0.0001 |
CT (123) | 12,777 | (43.02) | 12,815 | (41.30) | 174.49 | 0.0013 | 30.1% | 1.04 [1.01, 1.07] | 0.0028 |
Caucasian (60) | 7402 | (44.41) | 6448 | (43.20) | 47.63 | 0.8555 | 0% | 1.01 [0.98, 1.04] | 0.48 |
East Asian (32) | 3338 | (46.93) | 4439 | (46.87) | 53.81 | 0.0067 | 42.4% | 1.03 [0.98, 1.09] | 0.27 |
South Asian (13) | 634 | (25.62) | 531 | (19.22) | 27.60 | 0.0063 | 56.5% | 1.32 [1.12, 1.57] | 0.0011 |
Mixed Group (3) | 415 | (43.64) | 327 | (38.38) | 1.44 | 0.4874 | 0% | 1.02 [0.90, 1.15] | 0.78 |
Middle Eastern (7) | 489 | (38.66) | 593 | (34.42) | 5.67 | 0.4607 | 0% | 1.18 [1.07, 1.30] | 0.0011 |
Hispanic (2) | 165 | (46.74) | 157 | (43.13) | 1.88 | 0.1709 | 46.7% | 1.08 [0.92, 1.27] | 0.34 |
African (6) | 334 | (38.22) | 320 | (34.41) | 9.31 | 0.0975 | 46.3% | 1.13 [1.00, 1.28] | 0.0547 |
CC (123) | 13,108 | (44.14) | 14,883 | (47.97) | 269.85 | <0.0001 | 54.8% | 0.91 [0.89, 0.94] | <0.0001 |
Caucasian (60) | 7415 | (44.49) | 6998 | (46.89) | 63.45 | 0.3225 | 7% | 0.98 [0.95, 1.00] | 0.058 |
East Asian (32) | 2335 | (32.83) | 3589 | (37.89) | 89.99 | <0.0001 | 65.6% | 0.84 [0.77, 0.91] | <0.0001 |
South Asian (13) | 1748 | (70.63) | 2161 | (78.21) | 44.14 | <0.0001 | 72.8% | 0.91 [0.86, 0.96] | 0.0011 |
Mixed Group (3) | 443 | (46.58) | 437 | (51.29) | 1.09 | 0.5804 | 0% | 1.02 [0.92, 1.12] | 0.76 |
Middle Eastern (7) | 646 | (51.07) | 1041 | (60.42) | 16.22 | 0.0126 | 63% | 0.76 [0.66, 0.87] | <0.0001 |
Hispanic (2) | 86 | (24.36) | 101 | (27.75) | 0.04 | 0.8487 | 0% | 0.88 [0.69, 1.13] | 0.31 |
African (6) | 435 | (49.77) | 556 | (59.78) | 11.88 | 0.0365 | 57.9% | 0.87 [0.76, 1.00] | 0.0501 |
TT + CT (123) | 16,589 | (55.86) | 16,145 | (52.03) | 283.27 | <0.0001 | 56.9% | 1.09 [1.06, 1.11] | <0.0001 |
CC + CT (123) | 25,885 | (87.16) | 27,698 | (89.27) | 304.35 | <0.0001 | 59.9% | 0.98 [0.97, 0.99] | <0.0001 |
T (123) | 10,200 | (34.35) | 9737 | (31.38) | 180.11 | 0.0005 | 32.3% | 1.11 [1.07, 1.14] | <0.0001 |
C (123) | 19,496 | (65.65) | 21,290 | (68.62) | 172.23 | 0.0019 | 29.2% | 0.96 [0.94, 0.97] | <0.0001 |
Subgroups | |||||||||
TT Risk > 1 (87) 1 | 18,032 | (60.72) | 22,413 | (72.23) | |||||
TT | 2515 | (13.95) | 2351 | (10.49) | 163.42 | <0.0001 | 47.4% | 1.40 [1.28, 1.53] | <0.0001 |
CT | 7720 | (42.81) | 9243 | (41.24) | 148.57 | <0.0001 | 42.1% | 1.05 [1.02, 1.09] | 0.0029 |
CC | 7797 | (43.24) | 10,819 | (48.27) | 208.20 | <0.0001 | 58.7% | 0.88 [0.85, 0.91] | <0.0001 |
TT + CT | 10,235 | (56.76) | 11,594 | (51.73) | 225.28 | <0.0001 | 61.8% | 1.13 [1.09, 1.17] | <0.0001 |
CC + CT | 15,517 | (86.05) | 20,062 | (89.51) | 267.73 | <0.0001 | 67.9% | 0.96 [0.95, 0.98] | <0.0001 |
T | 6375 | (35.35) | 6972 | (31.11) | 134.06 | 0.0007 | 35.8% | 1.17 [1.12, 1.22] | <0.0001 |
C | 11,657 | (64.65) | 15,440 | (68.89) | 128.35 | 0.0021 | 33% | 0.94 [0.92, 0.95] | <0.0001 |
TT Risk < 1 (12) 2 | 2731 | (9.20) | 2156 | (6.95) | |||||
TT | 322 | (11.79) | 299 | (13.87) | 7.89 | 0.7229 | 0% | 0.86 [0.75, 1.00] | 0.051 |
CT | 1151 | (42.15) | 848 | (39.33) | 8.71 | 0.6489 | 0% | 1.04 [0.97, 1.12] | 0.23 |
CC | 1258 | (46.06) | 1009 | (46.80) | 11.75 | 0.3828 | 6.4% | 1.00 [0.95, 1.06] | 0.90 |
TT + CT | 1473 | (53.94) | 1147 | (53.20) | 11.24 | 0.4235 | 2.1% | 1.00 [0.95, 1.05] | 0.90 |
CC + CT | 2409 | (88.21) | 1857 | (86.13) | 13.30 | 0.2745 | 17.3% | 1.02 [1.00, 1.04] | 0.052 |
T | 897.5 | (32.86) | 723 | (33.53) | 6.66 | 0.8262 | 0% | 0.97 [0.90, 1.05] | 0.44 |
C | 1833.5 | (67.14) | 1433 | (66.47) | 7.30 | 0.7742 | 0% | 1.02 [0.98, 1.06] | 0.44 |
TT Risk~1 (24) 3 | 8934 | (30.08) | 6459 | (20.82) | |||||
TT | 975 | (10.91) | 680 | (10.53) | 18.02 | 0.7562 | 0% | 0.99 [0.90, 1.09] | 0.86 |
CT | 3906 | (43.72) | 2724 | (42.17) | 16.19 | 0.8468 | 0% | 1.01 [0.97, 1.05] | 0.73 |
CC | 4053 | (45.37) | 3055 | (47.30) | 17.43 | 0.7875 | 0% | 1.00 [0.96, 1.03] | 0.81 |
TT + CT | 4881 | (54.63) | 3404 | (52.70) | 16.51 | 0.8325 | 0% | 1.00 [0.97, 1.04] | 0.81 |
CC + CT | 7959 | (89.09) | 5779 | (89.47) | 18.51 | 0.7295 | 0% | 1.00 [0.99, 1.01] | 0.86 |
T | 2928 | (32.77) | 2042 | (31.61) | 8.89 | 0.9963 | 0% | 1.00 [0.95, 1.05] | 0.95 |
C | 6006 | (67.23) | 4417 | (68.39) | 9.19 | 0.9953 | 0% | 1.00 [0.98, 1.02] | 0.95 |
Variable | Partition Tree | Tukey’s Test | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
AICc | AP Death Levels | Count | Mean | SD | Levels Compared | Difference | SE Difference | Lower CI | Upper CI | p | |
TT%ct | 802 | 2 | 34 | 6.6 | 7.0 | 4/2 | 5.1 | 1.4 | 1.8 | 8.4 | 0.0011 |
3 and 4 | 89 | 11 | 6.0 | 3/2 | 4.5 | 1.5 | 1.1 | 8.0 | 0.0064 | ||
4/3 | 0.6 | 1.3 | −2.6 | 3.7 | 0.91 | ||||||
TT%ca | 857 | 2 and 3 | 74 | 11 | 6.8 | 4/2 | 6.1 | 1.7 | 1.9 | 10 | 0.0019 |
4 | 49 | 16 | 9.0 | 4/3 | 4.4 | 1.7 | 0.5 | 9.3 | 0.0251 | ||
3/2 | 1.7 | 1.8 | −2.6 | 6.0 | 0.63 | ||||||
CT%ct | 894 | 2 | 34 | 32 | 13 | 3/2 | 11 | 2.1 | 6.3 | 16 | <0.0001 |
3 and 4 | 89 | 43 | 7.0 | 4/2 | 9.9 | 2.0 | 5.1 | 15 | <0.0001 | ||
3/4 | 1.4 | 1.9 | −3.2 | 6.0 | 0.75 | ||||||
CT%ca | 887 | 2 | 34 | 39 | 12 | 4/2 | 8.0 | 2.0 | 3.3 | 13 | 0.0002 |
3 and 4 | 89 | 44 | 6.9 | 3/2 | 6.9 | 2.1 | 2.0 | 12 | 0.0031 | ||
4/3 | 1.1 | 1.9 | −3.3 | 5.6 | 0.82 | ||||||
CC%ct | 983 | 2 | 34 | 61 | 18 | 2/3 | 16 | 3.0 | 8.6 | 23 | <0.0001 |
3 and 4 | 89 | 46 | 11 | 2/4 | 15 | 2.9 | 8.1 | 22 | <0.0001 | ||
4/3 | 0.8 | 2.8 | −5.7 | 7.4 | 0.95 | ||||||
CC%ca | 997 | 2 | 34 | 53 | 18 | 2/4 | 14 | 3.0 | 6.9 | 21 | <0.0001 |
3 and 4 | 89 | 42 | 12 | 2/3 | 8.6 | 3.2 | 1.1 | 16 | 0.0211 | ||
3/4 | 5.5 | 2.9 | −1.3 | 12 | 0.14 | ||||||
TT + CT%ct | 983 | 2 | 34 | 39 | 18 | 3/2 | 16 | 3.0 | 8.6 | 23 | <0.0001 |
3 and 4 | 89 | 54 | 11 | 4/2 | 15 | 2.9 | 8.1 | 22 | <0.0001 | ||
3/4 | 0.8 | 2.8 | −5.7 | 7.4 | 0.9499 | ||||||
TT + CT%ca | 997 | 2 | 34 | 47 | 18 | 4/2 | 14 | 3.0 | 6.9 | 21 | <0.0001 |
89 | 58 | 12 | 3/2 | 8.6 | 3.2 | 1.1 | 16 | 0.0211 | |||
4/3 | 5.5 | 2.9 | −1.3 | 12 | 0.1410 | ||||||
RRTT | 373 | 2 | 29 | 1.8 | 1.7 | 2/3 | 0.6 | 0.3 | −0.1 | 1.2 | 0.11 |
3 and 4 | 89 | 1.4 | 0.9 | 2/4 | 0.3 | 0.3 | −0.3 | 1.0 | 0.42 | ||
4/3 | 0.2 | 0.3 | −0.4 | 0.8 | 0.60 | ||||||
RRCT | 137 | 2 | 34 | 1.3 | 0.8 | 2/3 | 0.3 | 0.1 | 0.1 | 0.6 | 0.0031 |
3 and 4 | 89 | 1.1 | 0.2 | 2/4 | 0.3 | 0.1 | 0.03 | 0.5 | 0.0244 | ||
4/3 | 0.1 | 0.1 | −0.1 | 0.3 | 0.65 | ||||||
RRTT + CT | 156 | 2 | 34 | 1.4 | 0.8 | 2/3 | 0.4 | 0.1 | 0.2 | 0.6 | 0.0007 |
3 and 4 | 89 | 1.1 | 0.2 | 2/4 | 0.3 | 0.1 | 0.04 | 0.5 | 0.0200 | ||
4/3 | 0.1 | 0.1 | −0.1 | 0.4 | 0.40 | ||||||
RRCC | −84 | 2 and 3 | 74 | 0.9 | 0.2 | 3/4 | 0.2 | 0.04 | 0.1 | 0.2 | 0.0001 |
4 | 49 | 0.9 | 0.2 | 3/2 | 0.1 | 0.04 | 0.03 | 0.2 | 0.0041 | ||
2/4 | 0.02 | 0.04 | −0.1 | 0.1 | 0.81 |
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Chen, Z.-F.; Young, L.; Yu, C.H.; Shiao, S.P.K. A Meta-Prediction of Methylenetetrahydrofolate-Reductase Polymorphisms and Air Pollution Increased the Risk of Ischemic Heart Diseases Worldwide. Int. J. Environ. Res. Public Health 2018, 15, 1453. https://doi.org/10.3390/ijerph15071453
Chen Z-F, Young L, Yu CH, Shiao SPK. A Meta-Prediction of Methylenetetrahydrofolate-Reductase Polymorphisms and Air Pollution Increased the Risk of Ischemic Heart Diseases Worldwide. International Journal of Environmental Research and Public Health. 2018; 15(7):1453. https://doi.org/10.3390/ijerph15071453
Chicago/Turabian StyleChen, Zhao-Feng, Lufei Young, Chong Ho Yu, and S. Pamela K. Shiao. 2018. "A Meta-Prediction of Methylenetetrahydrofolate-Reductase Polymorphisms and Air Pollution Increased the Risk of Ischemic Heart Diseases Worldwide" International Journal of Environmental Research and Public Health 15, no. 7: 1453. https://doi.org/10.3390/ijerph15071453