Table 7 Multivariate analysis to demonstrate genotype interaction of studied SNPs (based on their cellular functions) and influence of anti-VEGF treatment on AMD pathology. Results showed significant genotype interaction of pro-angiogenic genes including ADAMTS9 (rs6795735) and TIMP3 (rs5749482), but didn’t show direct influence of genotype interactions on number of anti-VEGF injections in Indian AMD patients.

From: Modulated anti-VEGF therapy under the influence of lipid metabolizing proteins in Age related macular degeneration: a pilot study

Multivariate tests

Genotype interactions

Effect

Test

Value

F

Hypothesis df

Error df

P-value

B3GALTL (rs9542236) * LIPC (rs920915)

Intercept

Pillai's Trace

.342

9.875

2

38

 < 0.0001

Anti-VEGF number

Pillai's Trace

.056

1.137

2

38

.331

B3GALTL genotype

Pillai's Trace

.011

.103

4

78

.981

LIPC genotype

Pillai's Trace

.475

6.078

4

78

 < 0.0001

B3GALTL * LIPC genotype

Pillai's Trace

.051

1.014

2

38

.372

APOE (rs769449) * HTRA1 (rs11200638)

Intercept

Wilks' Lambda

.260

58.273

2

41

 < 0.0001

Anti-VEGF number

Wilks' Lambda

.943

1.246

2

41

.298

APOE genotype

Wilks' Lambda

.810

4.795

2

41

.013

HTRA1 genotype

Wilks' Lambda

.781

2.695

4

82

.036

APOE * HTRA1

Wilks' Lambda

.835

1.938

4

82

.112

Pro-angiogenic genotype interaction

ADAMTS9 (rs6795735) * TIMP3 (rs5749482)

Intercept

Pillai's Trace

.698

46.138

2

40

 < 0.0001

Anti-VEGF number

Pillai's Trace

.006

.127

2

40

.881

ADAMTS9 Genotype

Pillai's Trace

.408

5.260

4

82

.001

TIMP3 genotype

Pillai's Trace

.370

11.751

2

40

 < 0.0001

ADAMTS9 * TIMP3 genotype

Pillai's Trace

.480

6.466

4

82

 < 0.0001

Regulatory genotype interaction

HTRA1 (rs11200638) * IER3 (rs3130783)

Intercept

Pillai's Trace

.189

4.090

2

35

.025

Anti-VEGF number

Pillai's Trace

.035

.640

2

35

.533

HTRA1 genotype

Pillai's Trace

.071

.666

4

72

.618

IER3 genotype

Pillai's Trace

.002

.028

2

35

.972

HTRA1 * IER3 genotype

Pillai's Trace

.033

.596

2

35

.557

Cellular function

SLC16A8 (rs8135665) * B3GALTL (rs9542236)

Intercept

Pillai's Trace

.100

2.271

2

41

.116

Anti-VEGF number

Pillai's Trace

.008

.175

2

41

.840

SLC16A8 genotype

Pillai's Trace

.091

.998

4

84

.413

B3GALTL

Pillai's Trace

.086

.941

4

84

.445

SLC16A8 * B3GALTL

Pillai's Trace

.007

.146

2

41

.864

Lipid metabolizing

APOE (rs769449) * LIPC (rs920915)

Intercept

Pillai's Trace

.324

8.871

2

37

.001

Anti-VEGF number

Pillai's Trace

.013

.249

2

37

.781

APOE genotype

Pillai's Trace

.006

.112

2

37

.895

LIPC genotype

Pillai's Trace

.057

.553

4

76

.697

APOE * LIPC

Pillai's Trace

.078

1.575

2

37

.221

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