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. 2015 Nov 23;9:2175–2193. doi: 10.2147/OPTH.S94508

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.