Table 3.
Results of overall population and ethnicity-based subgroup analysis of eNOS (4b/4a) polymorphism and DR risk in T2DM patients.
| Variables | N | References | Case/control | Genetic model | Fixed-effects model |
Random-effects model |
Heterogeneity |
Egger’s test (P) | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| OR (95%CI) | p Value | OR (95%CI) | p Value | PH | I2 (%) | |||||||
| Overall | Allelic model (a versus b) |
|||||||||||
| Total | 19 | [4,8,10,11,15,16,18,19,22–24,28,36–42] | 3859/3988 | 0.973(0.897–1.056) | .517 | 0.995(0.849–1.167) | .953 | 0.000 | 67.6% | 0.750 | ||
| HWE | 16 | [4,8,10,11,15,16,18,22,28,36–42] | 3585/3721 | 0.952(0.874 − 1.038) | .265 | 0.972(0.812–1.163) | .754 | 0.000 | 70.9% | 0.802 | ||
| Ethnicity | ||||||||||||
| Asians | Total | 11 | [4,8,10,11,16,19,23,28,40–42] | 2093/1986 | 0.925(0.826–1.035) | .173 | 0.934(0.766–1.138) | .496 | 0.025 | 51.2% | – | |
| HWE | 9 | [4,8,10,11,16,28,40–42] | 1819/1719 | 0.906(0.804–1.022) | .108 | 0.911(0.722–1.151) | .436 | 0.018 | 56.7% | – | ||
| Caucasians | Total/HWE | 5 | [15,22,36,37,39] | 1188/1102 | 1.284(1.094–1.506) | .002 | 1.273(1.006–1.610) | .045 | 0.084 | 51.4% | – | |
| Tunisians | Total | 2 | [24,38] | 510/599 | 0.841(0.691–1.024) | .085 | 0.958(0.523–1.755) | .891 | 0.008 | 85.9% | – | |
| Han Chinese | Total | 5 | [11,23,40–42] | 637/761 | 1.130(0.888–1.438) | .322 | 1.145(0.704–1.862) | .585 | 0.005 | 73.3% | – | |
| Overall | Recessive model(4a4b + 4b4b versus 4a4a) | |||||||||||
| Total | 19 | [4,8,10,11,15,16,18,19,22–24,28,36–42] | 3859/3988 | 0.990(0.809–1.210) | .918 | 0.969(0.738–1.271) | .818 | 0.198 | 21.1% | 0.969 | ||
| HWE | 16 | [4,8,10,11,15,16,18,22,28,36–42] | 3585/3721 | 0.981(0.791–0.217) | .863 | 0.944(0.712–1.253) | .692 | 0.259 | 17.0% | 0.767 | ||
| Ethnicity | ||||||||||||
| Asians | Total | 11 | [4,8,10,11,16,19,23,28,40–42] | 2093/1986 | 1.056(0.795–1.404) | .706 | 1.079(0.804–1.446) | .613 | 0.524 | 0.0% | – | |
| HWE | 9 | [4,8,10,11,16,28,40–42] | 1819/1719 | 1.107(0.820–1.494) | .507 | 1.098(0.809–1.490) | .550 | 0.761 | 0.0% | – | ||
| Caucasians | Total/HWE | 5 | [15,22,36,37,39] | 1188/1102 | 0.575(0.371–0.892) | .014 | 0.568(0.363–0.889) | .013 | 0.388 | 3.3% | – | |
| Tunisians | Total | 2 | [24,38] | 510/599 | 1.470(0.930–2.325) | .099 | 1.468(0.928–2.323) | .101 | 0.764 | 0.0% | – | |
| Han Chinese | Total | 5 | [11,23,40–42] | 637/761 | 0.710(0.323–1.562) | .394 | 0.694(0.302–1.594) | .389 | 0.697 | 0.0% | – | |
| Overall | Dominant model(4a4a + 4a4b versus 4b4b) | |||||||||||
| Total | 19 | [4,8,10,11,15,16,18,19,22–24,28,36–42] | 3859/3988 | 0.960(0.870–1.059) | .410 | 0.988(0.818–1.192) | .896 | 0.000 | 67.6% | 0.619 | ||
| HWE | 16 | [4,8,10,11,15,16,18,22,28,36–42] | 3585/3721 | 0.928(0.836–1.029) | .156 | 0.946(0.772–1.160) | .597 | 0.000 | 68.7% | 0.767 | ||
| Ethnicity | ||||||||||||
| Asians | Total | 11 | [4,8,10,11,16,19,23,28,40–42] | 2093/1986 | 0.903(0.788–1.036) | .145 | 0.925(0.749–1.142) | .468 | 0.057 | 44.1% | – | |
| HWE | 9 | [4,8,10,11,16,28,40–42] | 1819/1719 | 0.885(0.764–1.025) | .104 | 0.908(0.703–1.171) | .456 | 0.029 | 53.3% | – | ||
| Caucasians | Total/HWE | 5 | [15,22,36,37,39] | 1188/1102 | 1.268(1.052–1.528) | .013 | 1.264(0.991–1.614) | .060 | 0.163 | 38.8% | – | |
| Tunisians | Total | 2 | [24,38] | 510/599 | 0.860(0.676–1.094) | .220 | 1.118(0.404–3.092) | .830 | 0.001 | 91.7% | – | |
| Han Chinese | Total | 5 | [11,23,40–42] | 637/761 | 1.111(0.852–1.449) | .436 | 1.121(0.664–1.891) | .669 | 0.006 | 72.0% | – | |
| Overall | Additive model(4a4a + 4b4b versus 4a4b) | |||||||||||
| Total | 19 | [4,8,10,11,15,16,18,19,22–24,28,36–42] | 3859/3988 | 1.047(0.946–1.159) | .371 | 1.008(0.845–1.202) | .932 | 0.000 | 59.9% | 0.440 | ||
| HWE | 16 | [4,8,10,11,15,16,18,22,28,36–42] | 3585/3721 | 1.088(0.977–1.210) | .124 | 1.062(0.892–1.265) | .501 | 0.005 | 54.2% | 0.713 | ||
| Ethnicity | ||||||||||||
| Asians | Total | 11 | [4,8,10,11,16,19,23,28,40–42] | 2093/1986 | 1.097(0.954–1.261) | .195 | 1.073(0.892–1.291) | .453 | 0.199 | 25.7% | – | |
| HWE | 9 | [4,8,10,11,16,28,40–42] | 1819/1719 | 1.105(0.952–1.283) | .189 | 1.076(0.856–1.352) | .529 | 0.103 | 39.7% | – | ||
| Caucasians | Total/HWE | 5 | [15,22,36,37,39] | 1188/1102 | 0.865(0.712–1.050) | .143 | 0.865(0.703–1.064) | .170 | 0.345 | 10.8% | – | |
| Tunisians | Total | 2 | [24,38] | 510/599 | 1.046(0.814–1.344) | .724 | 0.738(0.213–2.562) | .633 | 0.000 | 93.3% | – | |
| Han Chinese | Total | 5 | [11,23,40–42] | 637/761 | 0.934(0.710–1.231) | .629 | 0.939(0.570–1.547) | .805 | 0.018 | 66.6% | – | |
| Overall | Homozygote model (4a4a versus 4b4b) | |||||||||||
| Total | 19 | [4,8,10,11,15,16,18,19,22–24,28,36–42] | 3859/3988 | 0.974(0.793–1.197) | .804 | 1.021(0.743–1.403) | .897 | 0.064 | 35.4% | 0.828 | ||
| HWE | 16 | [4,8,10,11,15,16,18,22,28,36–42] | 3585/3721 | 0.946(0.759–1.179) | .620 | 1.000(0.702–1.424) | 1.000 | 0.068 | 37.1% | 0.932 | ||
| Ethnicity | ||||||||||||
| Asians | Total | 11 | [4,8,10,11,16,19,23,28,40–42] | 2093/1986 | 0.889(0.663–1.193) | .433 | 0.867(0.639–1.174) | .356 | 0.456 | 0.0% | – | |
| HWE | 9 | [4,8,10,11,16,28,40–42] | 1819/1719 | 0.839(0.615–1.145) | .269 | 0.844(0.614–1.160) | .297 | 0.689 | 0.0% | – | ||
| Caucasians | Total/HWE | 5 | [15,22,36,37,39] | 1188/1102 | 1.833(1.176–2.856) | .007 | 1.827(1.127–2.961) | .014 | 0.331 | 13.1% | – | |
| Tunisians | Total | 2 | [24,38] | 510/599 | 0.722(0.453–1.150) | .170 | 0.742(0.408–1.352) | .330 | 0.209 | 36.8% | – | |
| Han Chinese | Total | 5 | [11,23,40–42] | 637/761 | 1.420(0.646–3.120) | .382 | 1.460(0.634–3.366) | .374 | 0.611 | 0.0% | – | |
| Overall | Heterozygote model (4a4b versus 4b4b) | |||||||||||
| Total | 19 | [4,8,10,11,15,16,18,19,22–24,28,36–42] | 3859/3988 | 0.952(0.858–1.055) | .347 | 0.990(0.820–1.196) | .920 | 0.000 | 64.3% | 0.464 | ||
| HWE | 16 | [4,8,10,11,15,16,18,22,28,36–42] | 3585/3721 | 0.915(0.821–1.021) | .112 | 0.938(0.773–1.137) | .513 | 0.001 | 61.3% | 0.735 | ||
| Ethnicity | ||||||||||||
| Asians | Total | 11 | [4,8,10,11,16,19,23,28,40–42] | 2093/1986 | 0.904(0.784–1.043) | .165 | 0.928(0.763–1.129) | .457 | 0.146 | 31.6% | – | |
| HWE | 9 | [4,8,10,11,16,28,40–42] | 1819/1719 | 0.892(0.765–1.039) | .142 | 0.919(0.723–1.169) | .493 | 0.073 | 44.3% | – | ||
| Caucasians | Total/HWE | 5 | [15,22,36,37,39] | 1188/1102 | 1.198(0.985–1.458) | .070 | 1.199(0.960–1.497) | .110 | 0.288 | 20.0% | – | |
| Tunisians | Total | 2 | [24,38] | 510/599 | 0.912(0.707–1.178) | .482 | 1.328(0.362–4.875) | .669 | 0.000 | 93.4% | – | |
| Han Chinese | Total | 5 | [11,23,40–42] | 637/761 | 1.079(0.819–1.421) | .590 | 1.075(0.645–1.793) | .780 | 0.014 | 68.1% | – | |
Note: N: number of studies; OR: odd ratio; 95%CI: 95% confidence intervals; HWE: Hardy–Weinberg equilibrium.
Bold indicates the P value was less than 0.05 and a significant association was found between eNOS (4a/4b) and the risk of incident DR.