Table 2.
Newer candidate gene studies and findings
| Gene | Polymorphism | Relation to diabetic retinopathy and significance level | Population and size (number of participants) | Methodology (self-reported vs clinically assessed) | References |
|---|---|---|---|---|---|
| Adiponectin (ADIPOQ) | rs2241766 (T45G) T allele | Positive assn w/DR in T2DM (P=0.0007) | Indian – NW population of Punjab – (672 pts) | Clinically assessed | 57 |
| rs266729 (C-11377G) rs822394 (A-4034C) rs1501299 (G276T) rs2241766 (T45G) |
No sig assn w/DR in T2DM No sig assn w/DR in T2DM No sig assn w/DR in T2DM No sig assn w/DR in T2DM |
Chinese (517 pts) | Clinically assessed | 58 | |
| CFH and CFB | rs1048709 (R150R) A allele in CFB rs800292 (I62V) A allele in CFH rs537160 (IVS7) G > A in CFB rs4151657 (IVS10) T > C in CFB rs2072633 (IVS17) A > G in CFB |
Positive assn w/DR in T2DM (P=0.035) Negative assn w/DR in T2DM (P=0.04) No sig assn w/DR in T2DM No sig assn w/DR in T2DM No sig assn w/DR in T2DM |
Chinese (552 pts) | Clinically assessed | 61 |
| rs1410996 | No sig assn w/PDR in T1DM | Spanish (147 pts) | Clinically assessed | 62 | |
| CHN2 | rs1002630 A allele rs1362363 G allele rs39059 rs2023908 |
Negative assn w/NPDR (OR =0.25, 95% CI =0.09–0.73) but not w/PDR in T2DM Negative assn w/DR (NPDR + PDR) in T2DM (OR =0.66, 95% CI =0.44–0.99) No sig assn w/DR in T2DM No sig assn w/DR in T2DM |
Taiwanese – Han Chinese – (719 pts) | Clinically assessed | 64 |
| rs39059 rs39075 |
No sig assn w/DR in T1DM No sig assn w/DR in T1DM |
US, demographics not reported (1,907 pts) | Clinically assessed | 65 | |
| EPO | rs507392 CC genotype rs551238 CC genotype rs1617640 |
Negative assn w/DR (P=0.027) and PDR (P=0.002) in T2DM Negative assn w/DR (P=0.016) and PDR (P=0.002) in T2DM No sig assn between NDR or PDR in T2DM |
Chinese (792 pts) | Clinically assessed | 67 |
| rs551238 rs1617640 |
No sig assn w/DR in T2DM No sig assn w/DR in T2DM |
Chinese (500 pts) | Clinically assessed | 48 | |
| rs1617640 | No sig assn w/DR in T1DM | US, demographics not reported (1,907 pts) | Clinically assessed | 65 | |
| GSTT1 and GSTM1 | Null genotype in GSTT1 Null genotype in GSTM1 |
Positive assn w/DR (NPDR + PDR) in T2DM (P<0.001) Negative assn w/DR in T2DM (P<0.001) |
Slovenian (604 pts) | Clinically assessed | 69 |
| Null genotype in GSTT1 Null genotype in GSTM1 |
No sig assn w/DR in T2DM Positive assn w/DR in T2DM (P=0.04) |
Iranian (115 pts) | Clinically assessed | 70 | |
| Null genotype in GSTT1 Null genotype in GSTM1 |
Positive assn w/DR (4 studies = T2DM, 1 study = T1DM; P<0.0001) Positive assn w/DR (3 studies = T2DM, 1 study = T1DM; P=0.0005) |
Caucasian (meta-analysis of 5 studies – report 3,563 pts, but actually comprise 3,463 pts based on studies included in meta-analysis) | Not reported | 71 | |
| Null genotype in GSTT1 Null genotype in GSTM1 |
No sig assn w/DR in T2DM No sig assn w/DR in T2DM |
Southern Iranian (605 pts) | Clinically assessed | 72 | |
| ICAM-1 | rs5498 (K469E) AA genotype | Positive assn w/DR in T2DM (P=0.012) | South Indian (356 pts) | Clinically assessed | 74 |
| rs5498 (K469E) (GG + AG vs AA) | Negative assn w/PDR in T2DM in Asian pts only (P=0.016); no sig assn w/DR in T2DM | Asian (meta-analysis of 7 studies – 2076 pts); assn w/PDR was found using 3 studies comprising 1,232 pts | Clinically assessed | 75 | |
| rs1799969 (G241R or +241G/A) | No sig assn w/DR in T2DM | Chinese (500 pts) | Clinically assessed | 48 | |
| rs5498 (K469E) | No sig assn w/DR in DM (T1 and T2) | 4 Asian and 3 Caucasian (meta-analysis of 7 studies – 3,411 pts) | Not reported | 76 | |
| rs5498 (K469E) | No sig assn w/DR in T2DM | 6 Asian +1 Caucasian study (meta-analysis of 7 studies – 2,003 pts) | Not reported | 77 | |
| IFN-γ | rs2430561 (+874 T/A) T allele | Positive assn w/PDR in T2DM (P=0.0011) | Asian (Indian, Bengali Hindu – 493 pts) | Clinically assessed | 44 |
| rs2430561 (+874 T/A) | No sig assn w/DR in T2DM | Brazilian (102 pts) | Clinically assessed | 79 | |
| IL-6 and IL-10 | rs1800896 (−1082) G allele in IL-10 rs1800795 (−174G/C) in IL-6 |
Positive assn w/PDR in T2DM (P=0.0048) No sig assn w/PDR in T2DM |
Bengali Hindu (493 pts) | Clinically assessed | 80 |
| rs1800896 (−1082 G/A) in IL-10 rs1800871 (−819C/T) in IL-10 rs1800872 (−592C/A) in IL-10 rs1800795 (−174C/G) in IL-6 |
No sig assn w/DR in T2DM No sig assn w/DR in T2DM No sig assn w/DR in T2DM No sig assn w/DR in T2DM |
Brazilian (102 pts) | Clinically assessed | 79 | |
| MCP-1 | rs1024611 (−2518 A/G) AA genotype | Positive assn w/PDR in T2DM (P=0.009) | Korean (590 pts) | Clinically assessed | 82 |
| rs1024611 (−2518 A/G) G allele | Positive assn w/PDR (P=0.02) but not NPDR in T2DM | Han Chinese (1,043 pts) | Clinically assessed | 83 | |
| rs1024611 (−2518 A/G) G allele | Increased onset of DR associated w/increased number of G alleles in T2DM (P=0.030) | Japanese (758 pts) | Clinically assessed | 84 | |
| rs1024611 (−2518 A/G) G allele | Positive assn w/PDR (P=0.007) and NPDR (P=0.026) in T2DM | Han Chinese (517 pts) | Clinically assessed | 85 | |
| MnSOD | A16V (C47T) AV genotype | Positive assn w/DR (P<0.0001) [Type of DM not specified in abstract, original article in Russian] | North Iranian (280 pts) | Not reported in abstract, original article in Russian | 87 |
| A16V (C47T) | No sig assn w/DR in T2DM | North Indian (758 pts) | Clinically assessed | 41 | |
| PAI-1 | −675 4G/5G, 4G4G genotype | Positive assn w/DR in T2DM in Caucasians (P=0.003) but not Asians | Caucasian, Asian, and Pima Indians (meta- analysis of 9 studies – 2,676 pts) | Not reported | 90 |
| −675 4G/5G | No sig assn w/DR in T1DM (Asian descent) or in T2DM (European descent) | Asian and European (meta-analysis of 10 studies – 5,768 pts) | Not reported | 91 | |
| PPARγ | rs1801282 (Pro12Ala) 12Ala allele | Negative assn w/DR in T2DM in Caucasian subgroup (P=0.01) but not in Asian subgroup (P=0.12) | 6 Caucasian studies and 2 Asian studies (meta-analysis of 8 studies – 5,170 pts) | Clinically assessed | 94 |
| rs1801282 (Pro12Ala) 12Ala allele | Negative assn w/PDR (OR =0.4, 95% CI =0.2–0.8) but not NPDR in T2DM | Pakistani (573 pts) | Clinically assessed | 95 | |
| rs1801282 (Pro12Ala) rs3856806 rs12497191 |
No sig assn w/DR or PDR in T2DM No sig assn w/DR or PDR in T2DM No sig assn w/DR or PDR in T2DM |
Chinese (792 pts) | Clinically assessed | 97 | |
| rs1801282 (Pro12Ala) | No sig assn w/DR in T1DM | US, demographics not reported (1,907 pts) | Clinically assessed | 65 | |
| rs1801282 (Pro12Ala) | No sig assn w/DR in T1DM | Finnish (2,963 pts) | Clinically assessed | 96 | |
| TCF7L2 | rs7903146 rs12255372 rs7901695 |
Positive assn w/DR in T2DM (P=0.037) Positive assn w/DR in T2DM (P=0.014) No sig assn w/DR in T2DM |
Italian (325 pts) | Clinically assessed | 99 |
| rs7903146 T allele | Positive assn w/PDR in T2DM (P=0.001) but not in T1DM | Caucasian (1,139 T2DM pts and 789 T1DM pts) | Clinically assessed | 100 | |
| rs7903146 | No sig assn w/DR in T2DM | African Americans, Caucasians, Polish, and Asian (review of 3 studies +1 abstract – 1,000+ pts) | Not reported | 102 | |
| rs6585205 rs7903146 rs11196218 |
No sig assn w/DR in T2DM No sig assn w/DR in T2DM No sig assn w/DR in T2DM |
Chinese (1,129 pts) | Not reported in abstract, original article in Chinese | 101 | |
| rs7903146 | No sig assn w/DR in T1DM | Finnish (2,963 pts) | Clinically assessed | 96 | |
| rs11196205 | No sig assn w/DR or PDR in T2DM | Chinese (792 pts) | Clinically assessed | 97 | |
| TGF-β1 | rs1800471 (R25P) (+915G/C) G allele rs1982073 (T869C) | Positive assn w/DR in T2DM (P=0.018) No sig assn w/DR in T2DM |
Brazilian (102 pts) | Clinically assessed | 79 |
| rs1982073 (T869C) (L10P) L allele rs1800469 (−509 C/T) rs1800468 (−800 G/A) |
Negative assn w/DR in T2DM (P=0.03) No sig assn w/DR in T2DM No sig assn w/DR in T2DM | Czech, Polish, and Indian (meta-analysis of 3 studies – 1,101 pts total) | Clinically assessed | 105 | |
| rs1982073 (T869C) rs1800471 (R25P) (+915G/C) |
No sig assn w/DR in T1DM No sig assn w/DR in T1DM |
Caucasian (British – 361 pts) | Clinically assessed | 106 | |
| TLR4 | rs4986790 (Asp299Gly) rs4986791 (Thr399Ile) rs10759931 (TLR4_1859) AG genotype rs1927914 (TLR4_2437) TC genotype rs1927911 (TLR4_7764) |
No sig assn w/DR in T2DM No sig assn w/DR in T2DM Positive assn w/DR in T2DM (P=0.04) Positive assn w/DR in T2DM (P=0.05) No sig assn w/DR in T2DM |
North Indian (698 pts) | Clinically assessed | 109 |
| rs1927914 C allele rs10759931 (TLR4_1859) rs1927911 (TLR4_7764) |
Positive assn w/DR in T2DM (P=0.018) No sig assn w/DR in T2DM No sig assn w/DR in T2DM |
Han Chinese (510 pts) | Clinically assessed | 110 | |
| TNF-α | rs1800629 (TNF-308 G/A) A allele | Positive assn w/PDR in T2DM (P=0.035) | Caucasian-Brazilian (745 pts) | Clinically assessed | 112 |
| rs361525 (TNF-238) A allele rs1800629 (TNF-308 G/A) | Positive assn w/PDR in T2DM (P=0.0001) No sig assn w/PDR in T2DM | Bengali Hindu (493 pts) | Clinically assessed | 80 | |
| rs1800629 (TNF-308 G/A) | No sig assn w/DR in T2DM | Indian (Punjab; NW India – 672 pts) | Clinically assessed | 57 | |
| rs1800629 (TNF-308 G/A) | No sig assn w/DR in T2DM | Brazilian (102 pts) | Clinically assessed | 79 | |
| rs1800629 (TNF-308 G/A) | No sig assn w/DR in T2DM | Asian and European (meta-analysis of 5 studies – 3041 pts) | Not reported | 113 | |
| UCP1 and UCP2 | rs1800592 (−3826A/G), G/G genotype in UCP1 | Positive assn w/DR in T1DM (P=0.043) | Brazilian (257 pts) | Clinically assessed | 115 |
| rs1800592 (−3826A/G), G/G genotype in UCP1 | Positive assn w/PDR (P=0.03) but not NPDR in T2DM | Chinese (792 pts) | Clinically assessed | 97 | |
| rs659366 866 G allele in promoter region in UCP2 rs660339 Ala55Val in exon 4 in UCP2 |
Positive assn w/PDR (P=0.016) but not NPDR in T2DM No sig assn w/PDR/NPDR in T2DM |
Chinese (958 pts) | Clinically assessed | 116 |
Abbreviations: T2DM, type 2 diabetes mellitus; DR, diabetic retinopathy; NW, north west; CFH, complement factor H; CFB, complement factor B; PDR, proliferative diabetic retinopathy; CHN2, chimerin 2; NPDR, nonproliferative diabetic retinopathy; OR, odds ratio; CI, confidence interval; EPO, erythropoietin; GSTT1, glutathione S-transferase theta 1; GSTM1, glutathione S-transferase mu 1; ICAM-1, intercellular adhesion molecule-1; T1DM, type 1 diabetes mellitus; IFN-γ, interferon gamma; IL-6, interleukin-6; IL-10, interleukin-10; MCP-1, monocyte chemoattractant protein-1; PAI-1, plasminogen activator inhibitor-1; PPARγ, peroxisome proliferator-activated receptor gamma; TCF7L2, transcription factor 7-like-2; TGF-β1, transforming growth factor beta 1; TLR4, toll-like receptor 4; TNF-α, tumor necrosis factor alpha; MnSOD, manganese superoxide dismutase; UCP1, uncoupling protein 1; UCP2, uncoupling protein 2; assn, association; sig, significant; pts, participants; w/, with.