Table 2.
Candidate Gene Studies with Multiple Independent Replication
| Gene | Polymorphism | Author | Year | Sample size | Population | Diabetes Type | Adjustment/ Matching for confounders | Significance | Comments |
|---|---|---|---|---|---|---|---|---|---|
| ALR2 | (CA)n | Lee at.al (35) | 2001 | 384 | Hong Kong Chinese | 2 | Yes | P<0.05 | Implicated, but unlikely to play major role |
| (CA)n | Ko et.al (36) | 1995 | 44 | Hong Kong Chinese | 2 | Yes | P=0.007 | ||
| (CA)n | Fujisawa et.al (38) | 1999 | 170 | Japanese | 2 | Yes | P=0.029 | ||
| (CA)n | Ichikawa et.al (39) | 1999 | 117 | Japanese | 2 | No | P=0.039 | ||
| (CA)n | Ikegishi et.al(40) | 1999 | 61 | Japanese | 2 | Yes | P=0.004 | Small sample size | |
| (CA)n | Wang at.al (37) | 2003 | 738 | Mainland Chinese | 2 | Yes | P=0.02 | ||
| (CA)n | Kumaramanickavel et.al (41) | 2003 | 214 | Indians | 2 | Yes | P=0.03 | ||
| (CA)n | Olmos et.al(42) | 2000 | 271 | Chileans | 2 | Yes | P=0.04 | ETDRS scale used | |
| (CA)n | Richeti et.al(43) | 2007 | 64 | Brazillian | 1 | No | P=0.014 | NPDR vs PDR | |
| T allele | Wang at.al (37) | 2003 | 738 | Mainland Chinese | 2 | Yes | P=0.02 | ||
| VEGF | C-634G | Awata et.al(48) | 2002 | 268 | Japanese | 2 | Yes | P<0.0018 | VEGF serum levels were significantly higher in healthy subjects with the CC genotype |
| C-634G | Awata et.al(54) | 2005 | 378 | Japanese | 2 | Yes | P=0.047 for macular edema | Results for macular edema independent of those for diabetic retinopathy | |
| C-634G | Uthra et.al(49) | 2008 | 213 | Indian | 2 | No | P=0.02 | Only in patients with microalbuminuria | |
| C-634G | Suganthalakshmi et.al(50) | 2006 | 210 | Indian | 2 | Yes | P=0.02 | C(-7)T, T(-1498)C polymorphisms also associated. | |
| C-634G | Szaflik et.al(53) | 2008 | 215 | Caucasian | 2 | No | P<0.05 | -460C not associated | |
| -460C | Ray et.al(51) | 2004 | 267 | Caucasian | 1 & 2 | Yes | P=0.027 | Polymorphism increases basal VEGF promoter activity by 71% | |
| -460C | Churchill et.al(52) | 2008 | 106 | Caucasian | 1 & 2 | Yes | 14-SNP haplotype P=0.006 | Haplotype analyses showed strong associations | |
| Multiple SNPs in VEGF-A | Al Kateb et.al(55) | 2007 | 1,369 | Caucasian from DCCT | 1 | Yes | P<0.05 | Follow-up of DCCT population (Incident severe retinopathy) | |
| I/D | Buraczynska et.al(56) | 2007 | 919 | Caucasian | 2 | Yes | P<0.001 | ||
| RAGE | Gly82Ser | Kumaramanickavel et.al(61) | 2002 | 200 | Indian | 2 | Only age | P=0.03 | |
| -429T/C | Hudson et.al(62) | 2001 | 215 | Caucasian | 2 | No | P=0.012 | Functional studies show differences in polymorphic receptor activity | |
| -374T/A | Ramprasad et.al(60) | 2007 | 339 | Indian | 2 | No | P<0.05 | No association with -429T/C | |
| -374 T/A | Lindholm et.al(59) | 2006 | 3,539 | Caucasian | 1 | Yes | P=0.03 | May be interaction with glycosylated hemoglobin |