Table 1.
Pooled meta-analysis: MTHFR C677T polymorphism genotypes and risks of AD by race-ethnicity.
| Genotype (Number of Studies) | AD Case N = 4732 n (%) | Control N = 5979 n (%) | Test of Heterogeneity | Statistical Model | Test of Association | |||
|---|---|---|---|---|---|---|---|---|
| Q | p | I2 (%) | Risk Ratio (95% CI) | p | ||||
| TT (44) | 822 (17.37) | 925 (15.47) | 58.28 | 0.0600 | 26.2 | Fixed | 1.13 (1.04, 1.23) | 0.0047 |
| Caucasian (13) | 268 (15.76) | 219 (14.53) | 10.00 | 0.6158 | 0 | Fixed | 1.04 (0.88, 1.22) | 0.6605 |
| East Asian (20) | 486 (21.39) | 633 (18.39) | 29.15 | 0.0636 | 34.8 | Fixed | 1.19 (1.07, 1.32) | 0.0015 |
| South Asian (4) | 15 (5.08) | 14 (3.18) | 4.24 | 0.2364 | 29.3 | Fixed | 1.36 (0.66, 2.81) | 0.4045 |
| Mixed (2) | 9 (7.20) | 15 (7.11) | 2.56 | 0.1098 | 60.9 | Fixed | 1.01 (0.43, 2.33) | 0.9906 |
| Middle Eastern (3) | 35 (13.57) | 33 (13.36) | 5.84 | 0.0539 | 65.8 | Fixed | 0.99 (0.64, 1.53) | 0.9593 |
| African (2) | 9 (11.11) | 11 (8.33) | 3.34 | 0.0678 | 70.0 | Fixed | 1.14 (0.41, 3.21) | 0.8016 |
| CT (44) | 2246 (47.46) | 2607 (43.60) | 67.85 | 0.0092 | 36.6 | Random | 1.12 (1.06, 1.19) | <0.0001 |
| Caucasian (13) | 803 (47.21) | 659 (43.73) | 6.33 | 0.8986 | 0 | Fixed | 1.07 (0.99, 1.15) | 0.0864 |
| East Asian (20) | 1089 (47.93) | 1604 (46.60) | 32.15 | 0.0301 | 40.9 | Random | 1.08 (1.00, 1.17) | 0.0638 |
| South Asian (4) | 118 (40.00) | 108 (24.55) | 5.74 | 0.1249 | 47.7 | Fixed | 1.56 (1.25, 1.95) | <0.0001 |
| Mixed (2) | 71 (56.80) | 101 (47.87) | 1.46 | 0.2263 | 31.7 | Fixed | 1.21 (0.98, 1.48) | 0.0704 |
| Middle Eastern (3) | 124 (48.06) | 86 (34.82) | 1.32 | 0.5156 | 0 | Fixed | 1.35 (1.09, 1.66) | 0.0052 |
| African (2) | 41 (50.62) | 49 (37.12) | 0.47 | 0.4920 | 0 | Fixed | 1.50 (1.10, 2.04) | 0.0107 |
| CC (44) | 1664 (35.16) | 2447 (40.93) | 61.63 | 0.0325 | 30.2 | Random | 0.85 (0.80, 0.90) | <0.0001 |
| Caucasian (13) | 630 (37.04) | 629 (41.74) | 11.43 | 0.4926 | 0 | Fixed | 0.91 (0.84, 0.99) | 0.0335 |
| East Asian (20) | 697 (30.68) | 1205 (35.01) | 21.75 | 0.2969 | 12.6 | Fixed | 0.84 (0.78, 0.91) | <0.0001 |
| South Asian (4) | 162 (54.92) | 318 (72.27) | 19.47 | 0.0002 | 84.6 | Random | 0.78 (0.59, 1.04) | 0.0937 |
| Mixed (2) | 45 (36.00) | 95 (45.02) | 0.45 | 0.5036 | 0 | Fixed | 0.78 (0.59, 1.03) | 0.0828 |
| Middle Eastern (3) | 99 (38.37) | 128 (51.82) | 1.23 | 0.5395 | 0 | Fixed | 0.76 (0.63, 0.92) | 0.0054 |
| African (2) | 31 (38.27) | 72 (54.55) | 0.003 | 0.9564 | 0 | Fixed | 0.66 (0.48, 0.92) | 0.0150 |
| T (44) | 1945 (41.10) | 2228 (37.27) | 37.59 | 0.7044 | 0 | Fixed | 1.12 (1.06, 1.17) | <0.0001 |
| C (44) | 2787 (58.90) | 3751 (62.73) | 33.14 | 0.8608 | 0 | Fixed | 0.93 (0.90, 0.96) | <0.0001 |
| CC + CT (44) | 3910 (82.63) | 5054 (84.53) | 70.18 | 0.0055 | 38.7 | Random | 0.98 (0.96, 1.00) | 0.0624 |
| TT + CT (44) | 3068 (64.84) | 3532 (59.07) | 70.84 | 0.0048 | 39.3 | Random | 1.11 (1.07, 1.16) | <0.0001 |
| Subgroups | ||||||||
| TT Risk > 1 | 4062 | 5205 | ||||||
| TT (37) | 761 (18.73) | 833 (16.00) | 44.31 | 0.1610 | 18.8 | Fixed | 1.19 (1.09, 1.30) | 0.0002 |
| CT (37) | 1906 (46.92) | 2278 (43.77) | 57.03 | 0.0143 | 36.9 | Random | 1.10 (1.04, 1.17) | 0.0023 |
| CC (37) | 1395 (34.34) | 2094 (40.23) | 56.40 | 0.0164 | 36.2 | Random | 0.84 (0.79, 0.90) | <0.0001 |
| CC + CT (37) | 3301 (81.27) | 4372 (84.00) | 55.24 | 0.0211 | 34.8 | Random | 0.97 (0.95, 0.99) | 0.0041 |
| TT + CT (37) | 2667 (65.66) | 3111 (59.77) | 66.60 | 0.0014 | 45.9 | Random | 1.12 (1.07, 1.17) | <0.0001 |
| TT Risk < 1 | 545 | 563 | ||||||
| TT (5) | 52 (9.54) | 77 (13.68) | 1.06 | 0.9000 | 0 | Fixed | 0.66 (0.47, 0.92) | 0.0142 |
| T (5) | 269 (49.36) | 228 (40.50) | 4.72 | 0.3177 | 15.2 | Fixed | 1.23 (1.07, 1.40) | 0.0025 |
| CC (5) | 224 (41.10) | 258 (45.83) | 3.60 | 0.4630 | 0 | Fixed | 0.90 (0.79, 1.04) | 0.1552 |
| CC + CT (5) | 493 (90.46) | 486 (86.32) | 0.87 | 0.9293 | 0 | Fixed | 1.06 (1.01, 1.10) | 0.0133 |
| TT + CT (5) | 321 (58.90) | 305 (54.17) | 3.60 | 0.4634 | 0 | Fixed | 1.08 (0.97, 1.20) | 0.1492 |
| TT Risk varied | 125 | 211 | ||||||
| TT (2) | 9 (7.20) | 15 (7.11) | 2.56 | 0.1098 | 60.9 | Fixed | 1.01 (0.43, 2.33) | 0.9906 |
| CT (2) | 71 (56.80) | 101 (47.87) | 1.46 | 0.2263 | 31.7 | Fixed | 1.21 (0.98, 1.48) | 0.0704 |
| CC (2) | 45 (36.00) | 95 (45.02) | 0.45 | 0.5036 | 0 | Fixed | 0.79 (0.60, 1.04) | 0.0960 |
| CC + CT (2) | 116 (92.80) | 196 (92.89) | 2.76 | 0.0964 | 63.8 | Fixed | 1.00 (0.94, 1.06) | 0.9902 |
| TT + CT (2) | 80 (64.00) | 116 (54.98) | 0.13 | 0.718 | 0 | Fixed | 1.18 (0.99, 1.41) | 0.0656 |
Note. Data included from 44 studies. Q = Cochran’s Q; AD = Alzheimer’s disease; CI = confidence interval; TT = homozygous mutation; CT = heterozygous mutation; CC = wild type; countries with TT risks > 1: Poland, Italy, Ireland, USA, Japan, South Korea, China, India, Egypt; countries with TT risks < 1: Sweden, Germany, Israel, Tunisia; countries with TT risks varied, ~1: Brazil.