Introduction
Materials and methods
Subjects
AMD | PCV | Control | p value | |
---|---|---|---|---|
No. of subjects | 100 | 100 | 190 | |
Male/female | 73:27 | 81:19 | 86:104 | 5.0 × 10−10
|
Mean ± SD | 74.56 ± 8.83 | 72.71 ± 8.25 | 72.22 ± 8.51 | 0.08 |
Range | 51–90 | 52–89 | 50–89 |
Genotyping
Statistical analyses
Logistic regression analysis and calculation of joint OR
Results
Genotyping of typical wet-type AMD and PCV
dbSNP ID (A/B) | Chr. | Position | Associated gene | SNP type | Case | Control | p value | Odds ratio (95% CI) | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
AA | AB | BB | AA | AB | BB | Allele | Minimum | Model | Allele | Recessive | Dominant | |||||
AMD | ||||||||||||||||
rs800292 (G/A) | 1 | 194,908,856 |
CFH
| Exon | 47 | 46 | 3 | 60 | 92 | 36 | 1.2 × 10−4
| 7.4 × 10−5
| Genotype | 2.08 (1.43 –3.04) | 7.34 (2.20 –24.52) | 2.05 (1.24–3.39) |
rs1329423 (G/A) | 1 | 194,913,010 |
CFH
| Intron | 35 | 50 | 15 | 47 | 87 | 55 | 0.0066 | 0.0049 | Trend | 1.63 (1.15 –2.31) | 2.33 (1.24 –4.38) | 1.63 (0.96–2.76) |
rs10737680 (T/G) | 1 | 194,946,078 |
CFH
| Intron | 43 | 49 | 8 | 58 | 88 | 44 | 0.0014 | 0.0012 | Dominant | 1.79 (1.25 –2.56) | 3.47 (1.56 –7.69) | 1.72 (1.04–2.84) |
rs742855 (G/A | 1 | 194,972,143 |
CFH
| Intron | 30 | 54 | 16 | 46 | 84 | 59 | 0.0183 | 0.0059 | Dominant | 1.52 (1.08 –2.15) | 2.38 (1.29 –4.42) | 1.33 (0.78–2.29) |
rs2736911 (G/A) | 10 | 124,204,345 |
HTRA1
| −6,686 | 80 | 20 | 0 | 108 | 74 | 6 | 1.1 × 10−4
| 4.8 × 110−5
| Trend | 2.67 (1.59 –4.49) | NA | 2.96 (1.68 –5.23) |
rs10490924 (A/C) | 10 | 124,204,438 |
HTRA1
| −6,593 | 52 | 30 | 18 | 20 | 84 | 85 | 4.5 × 10−15
| 4.1 × 10−14
| Recessive | 4.16 (2.89 –5.99) | 3.72 (2.07 –6.68) | 9.15 (4.99 –16.80) |
rs3750848 (C/A) | 10 | 124,205,305 |
HTRA1
| −5,726 | 52 | 30 | 18 | 20 | 84 | 84 | 5.1 × 10−15
| 4.6 × 10−14
| Recessive | 4.13 (2.86 –5.94) | 3.68 (2.05 –6.61) | 9.10 (4.96 –16.70) |
rs11200644 (A/G) | 10 | 124,220,931 |
HTRA1
| Intron | 76 | 23 | 0 | 105 | 79 | 6 | 3.9 × 10−4
| 1.7 × 10−4
| Trend | 2.40 (1.46 –3.93) | NA | 2.67 (1.55 –4.62) |
rs7093894 (C/A) | 10 | 124,224,870 |
HTRA1
| Intron | 73 | 27 | 0 | 88 | 86 | 15 | 4.2 × 10−6
| 3.0 × 10−6
| Trend | 2.84 (1.79 –4.50) | NA | 3.10 (1.83 –5.25) |
rs2672587 (C/G) | 10 | 124,225,345 |
HTRA1
| Intron | 47 | 38 | 15 | 29 | 85 | 74 | 2.0 × 10−10
| 2.2 × 10−9
| Trend | 3.16 (2.21 –4.53) | 3.68 (1.97 –6.85) | 4.86 (2.78 –8.49) |
rs2250804 (G/A) | 10 | 124,254,868 |
HTRA1
| Intron | 27 | 48 | 25 | 16 | 97 | 76 | 1.2 × 10−4
| 7.1 × 10−5
| Recessive | 2.01 (1.42 –2.85) | 2.02 (1.18 –3.46) | 4.00 (2.03 –7.86) |
rs2268356 (G/A) | 10 | 124,255,316 |
HTRA1
| Intron | 47 | 40 | 12 | 59 | 104 | 24 | 0.057 | 0.0068 | Recessive | 1.43 (1.00 –2.06) | 1.07 (0.51 –2.24) | 1.96 (1.19 –3.24) |
PCV | ||||||||||||||||
rs800292 (G/A) | 1 | 194,908,856 |
CFH
| Exon | 5 | 43 | 47 | 36 | 92 | 60 | 3.4 × 10−4
| 2.6 × 10−4
| Trend | 2.00 (1.37 –2.92) | 4.26 (1.61 –11.26) | 2.09 (1.26 –3.46) |
rs10490924 (A/C) | 10 | 124,204,438 |
HTRA1
| −6,593 | 32 | 50 | 18 | 20 | 84 | 85 | 3.0 × 10−8
| 3.7 × 10−8
| Trend | 2.72 (1.91 –3.86) | 3.72 (2.07 –6.68) | 3.98 (2.13 –7.43) |
rs3750848 (C/A) | 10 | 124,205,305 |
HTRA1
| −5,726 | 17 | 50 | 32 | 84 | 84 | 20 | 1.7 × 10−8
| 2.4 × 10−8
| Trend | 2.76 (1.93 –3.93) | 3.90 (2.15 –7.07) | 4.01 (2.14 –7.51) |
rs11200644 (A/G) | 10 | 124,220,931 |
HTRA1
| Intron | 72 | 26 | 2 | 105 | 79 | 6 | 0.0132 | 0.0055 | Recessive | 1.78 (1.13 –2.81) | 1.60 (0.32 –8.07) | 2.08 (1.24 –3.51) |
rs7093894 (C/A) | 10 | 124,224,870 |
HTRA1
| Intron | 4 | 29 | 67 | 15 | 86 | 88 | 0.0015 | 0.0012 | Recessive | 1.95 (1.28) | 2.07 (0.67 –6.41) | 2.33 (1.41 –3.86) |
rs2672587 (C/G) | 10 | 124,225,345 |
HTRA1
| Intron | 26 | 55 | 18 | 29 | 85 | 74 | 2.8 × 10−4
| 2.5 × 10−4
| Trend | 1.92 (1.35 –2.71) | 2.92 (1.62 –5.26) | 1.95 (1.07 –9.55) |
rs2241394 (G/C) | 19 | 6,636,260 | C3 | Intron | 0 | 6 | 93 | 2 | 33 | 154 | 0.0025 | 0.0037 | Trend | 3.47 (1.48 –8.38) | NA | 3.52 (1.43 –8.69) |
Analysis of the SNPs in ARMS2/HTRA1, CFH, C2/BF, C3, and CFI gene regions
dbSNP ID | Model | AMD | PCV | ||
---|---|---|---|---|---|
AIC | AIC difference | AIC | AIC difference | ||
Single | |||||
rs800292 | Gen | 349.6 | 352.1 | ||
Rec | 350.4 | 353.8 | |||
Dom | 359.6 | 357 | |||
rs10490924 | Gen | 317.9 | 347.8 | ||
Rec | 354.7 | 354.7 | |||
Dom | 318.4 | 357.4 | |||
rs2241394 | Gen | 375.4 | 366.7 | ||
Rec | 345.1 | 373 | |||
Dom | 374.7 | 365.3 | |||
Joint | |||||
rs800292gen + rs10490924gen | 291.8 | 0 | 325.9 | 5.5 | |
rs800292gen + rs2241394dom | 349.2 | 57.4 | 344 | 23.6 | |
rs10490924gen + rs2241394dom | 319.2 | 27.4 | 344 | 23.6 | |
rs800292gen + rs10490924gen + rs2241394dom | 293.4 | 1.6 | 320.4 | 0 |
Genotype combination | Number (%) | |||||||
---|---|---|---|---|---|---|---|---|
Control | Case | Odds ratio (95%CI) | p value | |||||
AMD | Single | |||||||
rs800292 | AA | 36 (0.19) | 3 (0.03) | 1 | ||||
AG | 92 (0.49) | 46 (0.48) | 6.00 (1.75–20.52) | 0.0011 | ||||
GG | 60 (0.32) | 47 (0.49) | 9.40 (2.73–32.42) | 2.3 × 10−5
| ||||
rs10490924 | CC | 85 (0.45) | 18 (0.18) | 1 | ||||
CA | 84 (0.44) | 30 (0.3) | 1.69 (0.87–3.26) | 0.1411 | ||||
AA | 20 (0.11) | 52 (0.52) | 12.28 (5.95–25.33) | 2.9 × 10−13
| ||||
Joint | ||||||||
rs10490924 | CC | rs800292 | AA | 15 (0.05) | 1 (0) | 1 | ||
AG | 38 (0.13) | 11 (0.04) | 3.09 (0.51–18.69) | 0.3234 | ||||
GG | 32 (0.11) | 5 (0.02) | 1.75 (0.26–11.74) | 1 | ||||
CA | AA | 15 (0.05) | 0 (0) | 0.33 (0.01–8.83) | 0.4866 | |||
AG | 45 (0.16) | 15 (0.05) | 3.52 (0.6–20.71) | 0.3353 | ||||
GG | 23 (0.08) | 14 (0.05) | 6.38 (1.05–38.54) | 0.061 | ||||
AA | AA | 6 (0.02) | 2 (0.01) | 3.97 (0.43–36.66) | 0.5633 | |||
AG | 8 (0.03) | 20 (0.07) | 24.92 (3.89–159.6) | 7.1 × 10−5
| ||||
GG | 5 (0.02) | 28 (0.1) | 53.55 (7.94–361.02) | |||||
PCV | Single | |||||||
rs800292 | GG | 36 (0.19) | 5 (0.05) | 1 | ||||
GA | 92 (0.49) | 43 (0.45) | 3.37 (1.23–9.18) | 0.0156 | ||||
AA | 60 (0.32) | 47 (0.49) | 5.64 (2.05–15.49) | |||||
rs10490924 | CC | 85 (0.45) | 18 (0.18) | 1 | ||||
CA | 84 (0.44) | 50 (0.5) | 2.81 (1.52–5.21) | 0.0008 | ||||
AA | 20 (0.11) | 32 (0.32) | 7.56 (3.55–16.08) | 6.0 × 10−8
| ||||
rs2241394 | CC + CG | 35 (0.19) | 6 (0.06) | 1 | ||||
GG | 154 (0.81) | 93 (0.94) | 3.52 (1.43–8.69) | 0.0041 | ||||
Joint | ||||||||
rs10490924 | CC | rs80092 | AA | 15 (0.05) | 0 (0) | 1 | ||
AG | 38 (0.13) | 7 (0.02) | 6.04 (0.32–112.28) | 0.0994 | ||||
GG | 32 (0.11) | 11 (0.04) | 10.97 (0.61–198.43) | 0.0253 | ||||
CA | AA | 15 (0.05) | 4 (0.01) | 9.00 (0.45–181.74) | 0.1131 | |||
AG | 45 (0.16) | 24 (0.09) | 16.69 (0.96–291.08) | 0.0043 | ||||
GG | 23 (0.08) | 21 (0.07) | 28.36 (1.6–503.36) | 0.0005 | ||||
AA | AA | 6 (0.02) | 1 (0) | 7.15 (0.26–199.68) | 0.1014 | |||
AG | 8 (0.03) | 12 (0.04) | 45.59 (2.39–869.16) | 0.0002 | ||||
GG | 5 (0.05) | 15 (0.05) | 87.36 (4.44–1,719.03) | 4.6 × 10−6
| ||||
rs10490924 | CC | rs2241394 | CC+CG | 15 (0.08) | 2 (0.02) | 1 | ||
GG | 70 (0.37) | 16 (0.16) | 1.71 (0.36–8.26) | 0.7302 | ||||
CA | CC+CG | 17 (0.09) | 2 (0.02) | 0.88 (0.11–7.06) | 1 | |||
GG | 67 (0.35) | 48 (0.48) | 5.37 (1.17–24.6) | 0.0172 | ||||
AA | CC+CG | 3 (0.02) | 2 (0.02) | 5.00 (0.49–50.83) | 0.2098 | |||
GG | 17 (0.09) | 29. (0.29) | 12.79 (2.6–62.88) | 0.0004 |