Table 2.
Summary of candidate gene studies of retinopathy of prematurity other than VEGFA
| Gene | Variant | Study country | Subjects | Results | Reference |
|---|---|---|---|---|---|
| ACE | rs1799752 | Italy | 299 ROP, 43 no ROP | No significant association | 43 |
| rs4291 | |||||
| 287-bp insertion in intron 16 | Kuwait | 74 ROP (53 regressed, 21 stage 4/5 ROP), 107 no ROP | The incidence of the II genotype was higher in ROP cases, while the incidence of the DD genotype was significantly higher in advanced stage ROP cases compared to spontaneously regressing ROP cases. (I, insertion, D, deletion) | 90 | |
| AGT | rs699 | Italy | 43 ROP, 299 no ROP | No significant association | 43 |
| AGTR1 | rs5186 | Italy | 43 ROP, 299 no ROP | No significant association | 43 |
| rs427832 | United States | 102 ROP, 228 no ROP | Significant association with ROP at p < 0.01 level of significance | 91 | |
| ANGPT2 | −35G>C | United States | Not specified | No significant association | 144 |
| Hungary | 90 treatment-requiring ROP, 110 no or mild (stage 1 or 2) ROP | No significant association | 145 | ||
| BDNF | rs7934165 rs2049046 |
United States | 126 treatment-requiring ROP, 467 stage 1/2 ROP | Two intronic SNPs found to be associated with difference between mild and threshold ROP | 146 |
| rs7934165 | United States | 140 treatment-requiring ROP, 1257 no or mild (stage 1 or 2) ROP | Meta-analysis of two studies provided evidence of association of variant with severe ROP | 146 | |
| CETP | rs289747 | United States | 102 ROP, 228 no ROP | Significant association with ROP at p < 0.01 level | 91 |
| CFH | rs52985 | United States | 102 ROP, 228 no ROP | Increased protection against ROP as number of T alleles increased (p = 0.01) | 91 |
| rs800292 | United States | 102 ROP, 228 no ROP | Increased protection against ROP as number of T alleles increased (p = 0.01) | 91 | |
| EPAS1 | rs1867785 | United States | 102 ROP, 228 no ROP | Significantly higher incidence of A allele in ROP | 91 |
| GP1BA | rs2243093 | United States | 102 ROP, 228 no ROP | Significant association with ROP at p < 0.01 level | 91 |
| LRP5 | rs143924910 (c.3656G>A), c.4148A>C, rs141407040 (c.4619C>T) |
Japan | 53 advanced ROP | Direct sequencing of coding regions of LRP5 revealed 3 nonsynonymous DNA variants in 3 patients. | 56 |
| 3-bp insertion in exon 1 | Japan | 17 advanced ROP, 51 no ROP | Single patient with advanced ROP shown to have 3 bp insertion in exon 1 CTG repeat area not observed in 28 unaffected patients. | 147 | |
| NOS3 | rs2070744 (−786T>C) |
Italy | 43 ROP, 299 no ROP | No significant association | 43 |
| Hungary | 105 treatment-requiring ROP, 127 stage 1 or 2 ROP | No significant association | 148 | ||
| United States | 15 ROP, 131 no ROP | significantly higher frequency of C allele in ROP | 149 | ||
| United States | 19 stage 4/5 ROP, 34 normal | significantly higher frequency of C allele in ROP | 150 | ||
| rs1799983 (894G>T) |
United States | 14 stage 4/5 ROP, 32 normal | No significant association | 150 | |
| United States | 15 ROP, 131 no ROP | significantly higher frequency of T allele in ROP | 149 | ||
| Italy | 43 ROP, 299 no ROP | No significant association | 43 | ||
| 27-bp VNTR in intron 4 (b/a) | United States | 15 stage 4/5, 32 normal controls | No significant association | 150 | |
| Hungary | 105 treatment-requiring ROP, 127 stage 1 or 2 ROP | The aa genotype presented an independent risk factor for ROP requiring treatment. | 148 | ||
| rs61722009 | Italy | 43 ROP, 299 no ROP | No significant association | 43 | |
| FLT1 | c.+6724(TG) 13–23 dinucleotide repeat | Japan | 127 ROP, 77 no ROP | No significant association | 140 |
| FZD4 | c.97 C>T; c.502 C>T (double missense mutation) |
United States | 93 ROP, 98 normal controls | Seven of 93 (7.5%) patients with ROP showed c.97 C>T; c.502 C>T double missense mutation. | 57 |
| rs80358282 (c.205C>T), rs184709254 (c.380G>A), c.631T>C |
Japan | 53 advanced ROP | Direct sequencing of coding regions of FZD4 revealed 3 nonsynonymous DNA variants in 4 patients. | 56 | |
| c.766A>G | Unspecified | 10 sporadic FEVR cases 20 advanced ROP cases |
PCR amplification of a large DNA fragment revealed one severe ROP case with c.766A>G. Significance not investigated. | 54 | |
| c.1109C>G, c.609G>T |
Canada | 71 severe ROP, 33 mild or no ROP | Direct sequencing of coding regions of FZD4 revealed 2 nonsynonymous DNA variants in 2 patients. | 55 | |
| HMOX1 | rs3074372 | Italy | 43 ROP, 299 no ROP | No significant association | 43 |
| IGF1R | c.3174G>A | United States | 52 stage 4/5 ROP, 33 normal controls | No significant association | 71 |
| Hungary | 108 treatment-requiring ROP, 120 stage 1 or 2 ROP, 164 normal controls | No significant association | 70 | ||
| IHH | rs3099 | United States | 102 ROP, 228 no ROP | Significant association with ROP at p < 0.01 level | 91 |
| IL10 | −1082G>A | Germany | 31 stage 1 or 2 ROP, 13 stage 3 ROP, 29 no ROP | No significant association | 76 |
| IL1B | +3953C>T | Germany | 31 stage 1 or 2 ROP, 13 stage 3 ROP, 29 no ROP | No significant association | 76 |
| KDR | 32G>A | Turkey | 42 treatment-requiring ROP, 50 regressed ROP, 31 normal controls | No significant association | 138 |
| g.+4422(AC)11–14 dinucleotide repeat | Japan | 127 ROP, 77 no ROP | No significant association | 140 | |
| NDP | Sequencing of all 3 exons and UTRs | United States | 54 severe ROP, 36 mild or no ROP, 22 normal controls, 31 normal parents | Six of 54 (11 %) infants with severe ROP had polymorphisms in the NDP. | 151 |
| Direct sequencing of coding regions and noncoding exon 1 | Japan | 53 advanced ROP | No meaningful sequence changes | 56 | |
| 237A>G | Japan | 17 advanced ROP, 51 no ROP | Single patient with AP-ROP found to have heterozygous substitution not observed in 51 unaffected cases | 147 | |
| 14 bp deletion in exon 1 | Australia | 31 ROP (Stage 2 or greater), 90 no ROP | Two twins with stage 3 regressed ROP and one unrelated patient with regressed stage 2 ROP displayed 14 bp deletion in CT repeat reagion. Also observed in a control patient. No statistical analysis. | 152 | |
| 5 bp deletion in exon 1 26C>G 71 bp deletion in exon 1 |
UK | 31 ROP stage 3 or more, 16 regressed ROP, 2 no ROP | One patient had 5 bp deletion and C>G transersion at +26, one patient had 71 bp deletion in same exon 1 region. No statistical analysis. | 61 | |
| 12 bp insertion in exon 1 14 bp deletion in exon 1 |
Japan | 100 advanced ROP (stage 4/5), 6 regressed stage 3 ROP, 130 no ROP | Two advanced ROP patients found to have disruptions in exon 1 of ND gene. No statistical analysis. | 59 | |
| 597C>A 110C>G |
Kuwait | 95 ROP, 115 no ROP | Significant association was found between ROP and 597C>A polymorphism. No significance found between 110C>G polymorphism and ROP. | 60 | |
| 121C>T R121W L108P |
United States | 16 ROP, 50 normal controls | One patient with a heterozygous base substitution, one pair of twins with novel R121W mutation, and one pair of twins with L108P missense mutation observed. No statistical analysis. | 58 | |
| TBX5 | rs1895602 | United States | 102 ROP, 228 no ROP | Significant association with ROP at p < 0.01 level | 91 |
| TGFB1 | −509C>T | United Kingdom | 91 treatment-requiring ROP, 97 stage 1/2 or no ROP | No significant association | 41 |
| TLR4 | rs4986790 (c.896A>G) |
Germany | 31 stage 1 or 2 ROP, 13 stage 3 ROP, 29 no ROP | No significant association | 76 |
| TNF | −308G>A | United Kingdom | 91 treatment-requiring ROP and 97 stage 1/2 or no ROP | No significant association | 41 |
| Germany | 31 stage 1 or 2 ROP, 13 stage 3 ROP, 29 no ROP | No significant association | 76 | ||
| TSPAN12 | Direct sequencing of coding regions of TSPAN12 | Japan | 53 advanced ROP | No meaningful sequence changes | 56 |