2012 Informa USA, Inc. DOI: 10.3109/13816810.2012.675398 Online supplementary material published in conjunction with S. Zhao et al.., Nitric oxide synthase 3 (NOS3) 4b/a, T-786C and G894T polymorphisms in association with diabetic retinopathy susceptibility: A meta-analysis. Ophthalmic Genetics, 2012 Supplementary material for <Zhao S, et al.>, < Nitric oxide synthase 3 (NOS3) 4b/a, T-786C and G894T polymorphisms in association with diabetic retinopathy susceptibility: A meta-analysis>, <Ophthalmic Genetics>, <2012> TABLE S1 Characteristics of studies included for investigation of associations between NOS3 4b/a and G894T, and T-786C polymorphisms and diabetic retinopathy risk Author Year Country/Ethnicity Study Design Genotyping method DM type Diagnostic method of DR Matched Total Genotyped Subjects Groups Sex (M/F) Age DM Duration Santos 2011 Brazil/ fluorescein angiography; age, duration of DM 630 for T-786C; Case 229/205 60.6±9.8 15.4 ± 8.9 596 for 4a/b; 623 for G894T Control 76/120 61.9±9.1 16.3 ± 7.0 Mehrab-Mohseni 2011 Iran/ CS PCR-aga 2 ophthalmoscopic examination ND 220 for 4a/b Case and control 63/157 53.05±10.4 ND Bazzaz 2010 UK/ CS PCR-RFLP 1 photography; ND 249 for T-786C Case Control ND ND 3 years Mamoulakis 2009 Greek/ Cohort PCR-aga 1 ND Gender 61 for 4b/a Case and control 35/26 Age at diagnosis 8.13 (0.25-17.3) Age at evaluation 15.6(5.0 29.1)
Ezzidi 2008 Tunisian/Mixed Fluorescein angiography; BMI, age at disease onset, duration of DM, SBP, 872 for each SNP Case 169/214 60.9±10.9 11.2 ± 4.6 Control 227/262 59.9±9.7 10.7 ± 5.6 DBP age at Case 131/85 66.8±10.4 13.9±8.3 disease onset, duration of DM, fasting Li 2008 Chinese/ CC PCR-Sequencing 2 plasma glucose, family history of DM, hypertension, 343 for G894T Control 77/50 68.8±11.2 14.7±4.8 hyperlipidemia, renal failure, current smoking HbA1c, systolic blood Case 133/150 66.0 ± 9.5 19.6 ± 8.9 pressure, Petrovicˇ 2008 Slovene/ CS PCR-aga 2 diastolic blood pressure, BMI, history of hypertension, 426 for 4b/a Control 57/86 66.9 ± 11.5 16.5 ± 6.6 smoking, total cholesterol, HDL
cholesterol, LDL cholesterol, triglycerides BMI, Case 34/34 54.7 ± 9.3 Chen 2007 USA/ African CS Pyrosequencing 2 waist-hip ratio, insulin, C-peptide, 369 for 4a/b; 373 for G894T Control 147/159 52.7 ± 10.9 ND glucose, HDL, TG, DBP DM duration, Case 30/26 59.5 ± 8.7 17.5 ± 5.8 smoking, BMI, de Syllos 2006 Brazil/ ; photography SBP, DBP, HbA1c, HDL, LDL, TG, 170 for each SNP Control 38/76 56.7 ± 10.3 15.3 ± 5.5 Ureia, Creatinine Suganthalakshmi 2006 Indian/ age at onset, duration of DM 210 for 4b/a Case 68/52 63 ± 7.2 15.5± 6.9 Control 70/20 59 ± 8.7 17 ±8.0 AWATA 2004 Japanese/ ; photography; fluorescein angiography gender, age at diagnosis, BMI, diastolic blood pressure, HbA1c, cholesterol, triglyceride, 226 for each SNP Case 56/61 58 ± 11 13 ± 8 Control 54/55 54 ± 15 7 ± 7 UKKOLA 2001 Finnish/ CS PCR-RFLP 2 ND 215 for G894T Case 126/113 58.3±11.0 8.6 ± 6.1
; photography and control Supplementary material for <Zhao S, et al.>, < Nitric oxide synthase 3 (NOS3) 4b/a, T-786C and G894T polymorphisms in association with diabetic retinopathy susceptibility: A meta-analysis>, <Ophthalmic Genetics>, <2012> TABLE S2 Pooled measures for the association between the NOS3 4b/a and G894T, and T-786C polymorphisms and susceptibility to non-proliferative or proliferative diabetic retinopathy Comparison Data Inherited model FEM Pooled OR (95% CI) P-value I 2 (%) P-value for heterogeneity 4b/a ba+aa vs.bb 0.846 (0.580-1.235) 0.386 10.2 0.291 aa vs.bb+ba 1.170 (0.430-3.188) 0.758 0 0.701 NPDR vs. NO a vs. b 0.895 (0.643-1.246) 0.511 14.1 0.281 aa vs.bb aa vs.ba 1.115 (0.408-3.045) 1.380 (0.479-3.978) 0.832 0 0.654 0.551 0 0.976 PDR vs. NO ba+aa vs.bb 0.992 (0.683-1.441) 0.967 0 0.701 aa vs.bb+ba 0.601 (0.186-1.939) 0.394 0 0.409
a vs. b aa vs.bb aa vs.ba ba+aa vs.bb aa vs.bb+ba PDR vs. NPDR a vs. b aa vs.bb aa vs.ba G894T TT+GT vs. GG TT vs. GG+GT NPDR vs. NO T vs. G TT vs. GG TT vs. GT PDR vs. NO TT+GT vs. GG 0.950 (0.682-1.321) 0.604 (0.186-1.963) 0.588 (0.178-1.943) 1.142 (0.776-1.680) 0.547 (0.177-1.694) 1.049 (0.746-1.473) 0.566 (0.182-1.766) 0.489 (0.153-1.562) 1.163 (0.821-1.647) 1.175 (0.596-2.314) 1.125 (0.853-1.483) 1.249 (0.620-2.514) 1.081 (0.533-2.191) 0.906 (0.632-1.298) 0.759 0 0.942 0.401 0 0.434 0.384 0 0.352 0.5 41.5 0.191 0.295 0 0.532 0.785 14 0.281 0.327 0 0.591 0.227 0 0.347 0.396 0 0.861 0.641 0 0.534 0.404 0 0.698 0.534 0 0.521 0.829 0 0.506 0.59 0 0.386
TT vs. GG+GT 1.122 (0.555-2.267) 0.749 0 0.372 T vs. G 0.954 (0.714-1.274) 0.751 31.6 0.227 TT vs. GG TT vs. GT 1.082 (0.525-2.230) 1.186 (0.566-2.484) 0.832 0 0.366 0.652 0 0.465 TT+GT vs. GG 0.798 (0.558-1.140) 0.214 0 0.548 PDR vs. NPDR -T786C NPDR vs. NO PDR vs. NO TT vs. GG+GT Excluded T vs. G 0.869 (0.656-1.151) TT vs. GG Excluded TT vs. GT Excluded CC+TC vs. TT 0.976 (0.684-1.395) CC vs. TT+TC 0.966 (0.610-1.530) C vs. T 0.977 (0.757-1.262) CC vs. TT 1.012 (0.609-1.682) CC vs. TC 0.940 (0.571-1.549) CC+TC vs. TT 0.894 (0.628-1.273) 0.328 0 0.482 0.896 36.8 0.208 0.883 0 0.856 0.861 24.2 0.251 0.962 0 0.755 0.809 0 0.801 0.534 0 0.904 CC vs. TT+TC 0.599 0.055 0 0.48
(0.355-1.011) C vs. T 0.821 (0.631-1.068) 0.124 0 0.979 CC vs. TT CC vs. TC 0.596 (0.338-1.051) 0.594 (0.340-1.040) 0.074 0 0.485 0.068 0 0.472 CC+TC vs. TT 0.898 (0.627-1.286) 0.556 39.4 0.199 CC vs. TT+TC 0.626 (0.377-1.041) 0.071 0 0.503 PDR vs. NPDR C vs. T 0.832 (0.641-1.081) 0.169 15.4 0.277 CC vs. TT CC vs. TC 0.593 (0.341-1.030) 0.645 (0.376-1.107) 0.064 0 0.57 0.112 0 0.34