TABLE 2.
Meta-analysis of genetic variants and risk for diabetic retinopathy in patients with type 1 diabetes, type 2 diabetes, and both types of diabetes, for studies of white populations
| Gene | Variant | Risk allele | Comparison | Type of diabetes | Total case subjects with risk allele (%) | Total control subjects with risk allele (%) | Weight | OR (95% CI) | SE | Number of studies | χ2 | P | References |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ACE | INS/DEL at intron 16 | 287 base pair deletion | No diabetic retinopathy vs. any diabetic retinopathy | Type 1 | 651 (55) | 458 (52) | 50.735 | 1.06 (0.88–1.27) | 0.09 | 6 | 3.67 | 0.5402 | (S1–S6) |
| Type 2 | 504 (53) | 501 (54) | 49.265 | 0.99 (0.83–1.19) | 0.09 | 4 | 1.43 | 0.9182 | (S7) (S8) (S10) (S3) | ||||
| Total | 1,155 (54) | 959 (53) | 100 | 1.02 (0.9–1.16) | 0.07 | 10 | 5.35 | 0.7157 | |||||
| No diabetic retinopathy vs. PDR | Type 1 | 387 (60) | 220 (55) | 76.8488 | 1.19 (0.77–1.86) | 0.23 | 4 | 8.01 | 0.4355 | (S1) (S2) (S4) (S5) | |||
| Type 2 | 75 (53) | 78 (49) | 23.1512 | 1.14 (0.73–1.79) | 0.23 | 1 | 0.00 | 0.5617 | (S10) | ||||
| Total | 462 (59) | 298 (53) | 100 | 1.19 (0.86–1.66) | 0.17 | 5 | 8.11 | 0.2995 | |||||
| NPDR vs. PDR | Type 1 | 120 (64) | 72 (45) | 33.9165 | 2.21 (1.44–3.39) | 0.22 | 1 | 0.00 | 0.0003 | (S4) | |||
| Type 2 | 156 (54) | 224 (50) | 66.0835 | 1.23 (0.9–1.67) | 0.16 | 2 | 0.83 | 0.1905 | (S10) (S14) | ||||
| Total | 276 (58) | 296 (49) | 100 | 1.52 (1–2.32) | 0.22 | 3 | 5.55 | 0.0509 | |||||
| NOS3 | rs3138808 | 393 base pair insertion | No diabetic retinopathy vs. any diabetic retinopathy | Type 1 | 21 (11) | 42 (22) | 47.0284 | 0.43 (0.24–0.76) | 0.29 | 1 | 0.00 | 0.0036 | (S16) |
| Type 2 | 123 (22) | 58 (21) | 52.9716 | 1.09 (0.77–1.55) | 0.18 | 1 | 0.00 | 0.6248 | (S21) | ||||
| Total | 144 (19) | 100 (21) | 100 | 0.71 (0.28–1.75) | 0.46 | 2 | 7.49 | 0.4512 | |||||
| VEGF | rs2010963 | G | No diabetic retinopathy vs. any diabetic retinopathy | Type 2 | 387 (55) | 247 (62) | 100 | 0.83 (0.65–1.07) | 0.13 | 2 | 0.43 | 0.1601 | (S27) (S28) |
| AKR1B1 | rs759853 | T | No diabetic retinopathy vs. any diabetic retinopathy | Type 1 | 99 (29) | 121 (46) | 45.1355 | 0.5 (0.35–0.71) | 0.18 | 2 | 0.01 | 0.0001 | (S30) (S31) |
| Type 2 | 324 (42) | 202 (41) | 54.8645 | 1.05 (0.83–1.33) | 0.12 | 2 | 0.91 | 0.6756 | (S33) | ||||
| Total | 423 (38) | 323 (43) | 100 | 0.76 (0.5–1.16) | 0.22 | 4 | 12.83 | 0.2061 | |||||
| AKR1B1 | (CA)n dinucleotide repeat | z | No diabetic retinopathy vs. any diabetic retinopathy | Type 1 | 277 (42) | 247 (39) | 75.2466 | 1.11 (0.88–1.39) | 0.117 | 3 | 0.88 | 0.3785 | (S30) (S37) (S39) |
| Type 2 | 79 (32) | 67 (42) | 24.7534 | 0.66 (0.44–1.00) | 0.21 | 1 | 0.00 | 0.05 | (S42) | ||||
| Total | 356 (39) | 314 (40) | 100 | 0.97 (0.73–1.27) | 0.14 | 4 | 5.47 | 0.8076 | |||||
| z | No diabetic retinopathy vs. PDR | Type 1 | 107 (43) | 127 (38) | 51.9056 | 1.24 (0.89–1.74) | 0.17 | 1 | 0.00 | 0.2008 | (S39) | ||
| Type 2 | 79 (32) | 67 (42) | 48.0944 | 0.66 (0.44–1.00) | 0.21 | 1 | 0.00 | 0.05 | (S42) | ||||
| Total | 186 (38) | 194 (39) | 100 | 0.92 (0.5–1.70) | 0.314 | 2 | 5.42 | 0.7872 | |||||
| z−2 | No diabetic retinopathy vs. any diabetic retinopathy | Type 1 | 226 (34) | 167 (27) | 74.1019 | 1.83 (0.85–3.95) | 0.393 | 3 | 15.42 | 0.1238 | (S30) (S37) (S39) | ||
| Type 2 | 97 (40) | 43 (27) | 25.8981 | 1.78 (1.15–2.74) | 0.22 | 1 | 0.00 | 0.0091 | (S42) | ||||
| Total | 323 (36) | 210 (27) | 100 | 1.80 (1.06–3.06) | 0.271 | 4 | 15.89 | 0.0301 | |||||
| z−2 | No diabetic retinopathy vs. PDR | Type 1 | 87 (35) | 121 (36) | 52.3594 | 0.96 (0.68–1.35) | 0.175 | 1 | 0.00 | 0.8023 | (S39) | ||
| Type 2 | 97 (40) | 43 (27) | 47.6406 | 1.78 (1.15–2.74) | 0.22 | 1 | 0.00 | 0.0091 | (S42) | ||||
| Total | 184 (37) | 164 (33) | 100 | 1.29 (0.7–2.36) | 0.309 | 2 | 4.85 | 0.4166 | |||||
| z+2 | No diabetic retinopathy vs. any diabetic retinopathy | Type 1 | 103 (16) | 159 (25) | 76.3483 | 0.51 (0.25–1.06) | 0.372 | 3 | 12.85 | 0.0722 | (S39) | ||
| Type 2 | 28 (12) | 24 (15) | 23.6517 | 0.73 (0.41–1.31) | 0.299 | 1 | 0.00 | 0.2958 | (S42) | ||||
| Total | 131 (15) | 183 (23) | 100 | 0.56 (0.32–0.97) | 0.282 | 4 | 13.71 | 0.039 | |||||
| z+2 | No diabetic retinopathy vs. PDR | Type 1 | 41 (17) | 57 (17) | 63.9459 | 0.97 (0.62–1.50) | 0.224 | 1 | 0.00 | 0.8814 | (S30) (S37) (S39) | ||
| Type 2 | 28 (12) | 24 (15) | 36.0541 | 0.73 (0.41–1.31) | 0.299 | 1 | 0.00 | 0.2958 | (S42) | ||||
| Total | 69 (14) | 81 (17) | 100 | 0.87 (0.62–1.24) | 0.179 | 2 | 0.56 | 0.455 |
Subanalyses were performed for NPDR and PDR if data were available. References are preceded with S as they correlate with the online supplementary appendix.