AMD Prognosis

Genetics of AMD

It is estimated that up to 70% of AMD risk is attributable to genetic variation [7]. Macula Risk PGx analyzes 15 AMD-associated genetic variants in 12 different genes. These genes are present across four biological pathways known to be involved in AMD pathogenesis: the complement system (CFH, C3, CFI, C2 and CFB), cholesterol metabolism (CETP, LIPC, ABCA1 and APOE), extracellular matrix remodeling (TIMP3 and COL8A1) and oxidative stress (ARMS2). All of the genetic markers in Macula Risk PGx have been validated in at least four independent publications involving tens of thousands of study subjects.

Gene

Number of
Studies

Number of
Study Subjects

CFH

46

135,047

ARMS2

35

136,003

CFI

12

74,984

C3

19

83,139

C2

19

75,210

CFB

20

78,096

LIPC

12

93,419

ABCA1

8

77,616

CETP

6

77,284

COL8A1

4

77,125

APOE

7

35,095

TIMP3

8

85,784

The following chart illustrates the risk level (low, medium or high) of each possible genotype at the 15 AMD-associated risk variants measured in Macula Risk PGx.

As research methods and the pool of patient samples improve, there are regular announcements of ‘new AMD markers’ being discovered. However, the more important finding of all these studies are not these new markers, but instead the enormous statistical weight and importance of the previously identified (particularly CFH and ARMS2) markers.

 
   

 Genotype

Gene

SNP

Low
Risk

Intermediate Risk

High
Risk

CFH

rs3766405/ rs412852 haplotypes

All
others

CC/CT
or CT/CT

CC/CC

CFH

rs1048663

AA

GA

GG

CFI

rs10033900

CC

CT

TT

C3

rs2230199

CC

CG

GG

C2

rs9332739

CC

CG

GG

CFB

rs541862

GG

AG

AA

LIPC

rs10468017

TT

CT

CC

ABCA1

rs1883025

TT

TC

CC

CETP

rs3764261

CC

CA

AA

COL8A1

rs13095226

CC

TC

TT

APOE

rs429358/rs7412 hap­lotypes

CC/CC

All others

TT/TT

TIMP3

rs9621532

CC

CA

AA

ARMS2*

372_815del443ins54

NN

ND

DD

*N = Normal, D = deletion

Note: this table is for reference purposes only.