Method for determining a therapeutic approach for the treatment of age-related macular degeneration (amd)

Abstract

Disclosed is a method for determining a supplement regime for a subject diagnosed with age-related macular degeneration (AMD). The method involves determining the subject's risk of developing advanced AMD based on their genetic profile for the complement factor H gene and the ARMS2 gene and administering a supplement containing antioxidants and/or zinc based on their risk of developing advanced AMD.

I claim: 
     
         1 . A method of determining a supplement regime for a subject diagnosed with age-related macular degeneration (AMD) comprising:
 (a) determining the subject's risk of developing advanced AMD in a sample from said subject based on their genetic profile for the complement factor H gene and the Age-Related Maculopathy Suspectibility 2 (ARMS2) gene and   (b) administering a supplement based on said determining step, wherein when the subject has zero risk alleles for CFH and 1 risk allele for ARMS the supplement is zinc/copper alone; wherein when the subject has 1 risk allele for CFH and zero risk alleles for ARMS2 the supplement is antioxidants alone; wherein when the subject has 0 risk alleles for CFH and two risk alleles for ARMS2 the supplement is zinc/copper alone; wherein when the subject has one risk allele for CFH and one risk allele for ARMS2 the supplement is both zinc/copper and antioxidants, wherein when the subject has 2 risk alleles for CFH and zero risk alleles for ARMS2 the supplement is antioxidants alone, wherein when the subject has one risk allele for the CFH gene and two risk alleles at the ARMS2 locus the supplement is zinc alone.   
     
     
         2 . The method of  claim 1 , wherein the subject diagnosed with age-related macular degeneration has one or more retinal drusen. 
     
     
         3 . The method of  claim 1 , wherein the subject's risk of developing advanced AMD is determined by analysing the single nucleotide polymorphisms: rs3766405 (SEQ ID NO: 1) and/or rs412852 (SEQ ID NO: 2) in the CFH gene and rs10690924 (SEQ ID NO: 22) or 372_815delins54 in the ARMS2 gene. 
     
     
         4 . The method of  claim 1 , wherein the subject's risk of developing advanced AMD is determined by analysing the single nucleotide polymorphisms: rs1048663 (SEQ ID NO:23), rs3766405 (SEQ ID NO: 1), rs412852 (SEQ ID NO: 2), rs11582939 (SEQ ID NO: 24) and/or rs1280514 (SEQ ID NO: 25) in the CFH gene and *372_815delins54 in the ARMS2 gene. 
     
     
         5 . The method of  claim 1 , wherein the subject's risk of developing advanced AMD is determined by analysing the single nucleotide polymorphism rs1061170 (SEQ ID NO: 3). 
     
     
         6 . The method of  claim 1 , wherein the subject's risk of developing advanced AMD is determined by analysing the single nucleotide polymorphism: rs1061170 (SEQ ID NO: 3), rs2274700 (SEQ ID NO: 4), rs403846 (SEQ ID NO: 5), rs12144939 (SEQ ID NO: 6), rs1409153 (SEQ ID NO: 7), rs1750311 ((SEQ ID NO: 8), rs10922153 (SEQ ID NO: 9), rs698859 (SEQ ID NO: 10), rs2990510 (SEQ ID NO: 11), rs3753394 (SEQ ID NO: 12), rs529825 (SEQ ID NO: 13), rs800292 (SEQ ID NO: 14), rs3766404 (SEQ ID NO: 15), rs1061147 (SEQ ID NO: 16), rs2033674 (SEQ ID NO: 17), rs3753396 (SEQ ID NO: 18), or rs1065489 (SEQ ID NO: 19) in the CFH gene, or a combination thereof. 
     
     
         7 . The method of  claim 1 , wherein the supplement comprises a multi-vitamin supplement. 
     
     
         8 . The method of  claim 3 , wherein the subject is considered at high risk of developing advanced AMD when the subject is homozygous for the C allele at rs3766405 (position 27 of SEQ ID NO: 1) and is homozygous for the C allele at rs412852 (position 27 of SEQ ID NO: 2). 
     
     
         9 . The method of  claim 10 , wherein the subject is considered at low risk of developing advanced AMD when the subject is homozygous for the C allele at rs3766405 (position 27 of SEQ ID NO: 1) and is homozygous for the T allele at rs412852 (position 27 of SEQ ID NO: 2), heterozygous for the C allele at rs3766405 (position 27 of SEQ ID NO: 1) and is homozygous for the C allele at rs412852 (position 27 of SEQ ID NO: 2), heterozygous for the C allele at rs3766405 (position 27 of SEQ ID NO: 1) and is homozygous for the T allele at rs412852 (position 27 of SEQ ID NO: 2), homozygous for the T allele at rs3766405 (position 27 of SEQ ID NO: 1) and is homozygous for the C allele at rs412852 (position 27 of SEQ ID NO: 2), homozygous for the T allele at rs3766405 (position 27 of SEQ ID NO: 1) and is heterozygous for the C allele at rs412852 (position 27 of SEQ ID NO: 2) or homozygous for the T allele at rs3766405 (position 27 of SEQ ID NO: 1) and is homozygous for the T allele at rs412852 (position 27 of SEQ ID NO: 2). 
     
     
         10 . The method of  claim 5 , wherein the subject is considered at high risk of developing advanced AMD when the subject is homozygous for the C allele at rs1061170 (position 27 of SEQ ID NO: 3). 
     
     
         11 . The method of  claim 5 , wherein the subject is considered at medium risk of developing advanced AMD when the subject is heterozygous for the C allele at rs1061170 (position 27 of SEQ ID NO: 3). 
     
     
         12 . The method of  claim 5 , wherein the subject is considered at low risk of developing advanced AMD when the subject is homozygous for the T allele at rs1061170 (position 27 of SEQ ID NO: 3). 
     
     
         13 . The method of  claim 6 , wherein the subject is considered at high risk of developing advanced AMD when the subject is homozygous for the C allele at rs1061170 (position 27 of SEQ ID NO: 3); when the subject is homozygous for the G allele at rs2274700 (position 27 of SEQ ID NO: 4); when the subject is homozygous for the A allele at rs403846 (position 27 of SEQ ID NO: 5); when the subject is homozygous for the G allele at rs12144939 (position 27 of SEQ ID NO: 24); when the subject is homozygous for the G allele at rs1409153 (position 27 of SEQ ID NO: 9); when the subject is homozygous for the C allele at rs1750311 (position 27 of SEQ ID NO: 8); when the subject is homozygous for the G allele at rs10922153 (position 27 of SEQ ID NO: 9); when the subject is homozygous for the A allele at rs698859 (position 27 of SEQ ID NO: 10); when the subject is homozygous for the T allele at rs2990510 (position 27 of SEQ ID NO: 11); when the subject is homozygous for the C allele at rs3753394 (position 27 of SEQ ID NO: 12); when the subject is homozygous for the C allele at rs529825 (position 27 of SEQ ID NO: 13); when the subject is homozygous for the T allele at rs800292 (position 27 of SEQ ID NO: 14); when the subject is homozygous for the C allele at rs3766404 (position 27 of SEQ ID NO: 15); when the subject is homozygous for the A allele at rs1061147 (position 27 of SEQ ID NO: 16); when the subject is homozygous for the T allele at rs2033674 (position 27 of SEQ ID NO: 17); when the subject is homozygous for the G allele at rs3753396 (position 27 of SEQ ID NO: 18); or when the subject is homozygous for the T allele at rs1065489 (position 27 of SEQ ID NO: 19). 
     
     
         14 . The method of  claim 6 , wherein the subject is considered at medium risk of developing advanced AMD when the subject is heterozygous for the C allele at rs1061170 (position 27 of SEQ ID NO: 3); when the subject is heterozygous for the G allele at rs2274700 (position 27 of SEQ ID NO: 4); when the subject is heterozygous for the A allele at rs403846 (position 27 of SEQ ID NO: 5); when the subject is heterozygous for the G allele at rs12144939 (position 27 of SEQ ID NO: 6); when the subject is heterozygous for the G allele at rs1409153 (position 27 of SEQ ID NO: 7); when the subject is heterozygous for the C allele at rs1750311 (position 27 of SEQ ID NO: 8); when the subject is heterozygous for the G allele at rs10922153 (position 27 of SEQ ID NO: 9); when the subject is heterozygous for the A allele at rs698859 (position 27 of SEQ ID NO: 10); when the subject is heterozygous for the T allele at rs2990510 (position 27 of SEQ ID NO: 11); when the subject is heterozygous for the C allele at rs3753394 (position 27 of SEQ ID NO: 12); when the subject is heterozygous for the C allele at rs529825 (position 27 of SEQ ID NO: 13); when the subject is heterozygous for the T allele at rs800292 (position 27 of SEQ ID NO: 14); when the subject is heterozygous for the C allele at rs3766404 (position 27 of SEQ ID NO: 15); when the subject is heterozygous for the A allele at rs1061147 (position 27 of SEQ ID NO: 16); when the subject is heterozygous for the T allele at rs2033674 (position 27 of SEQ ID NO: 17); when the subject is heterozygous for the G allele at rs3753396 (position 27 of SEQ ID NO: 18); or when the subject is heterozygous for the T allele at rs1065489 (position 27 of SEQ ID NO: 19). 
     
     
         15 . The method of  claim 6 , wherein the subject is considered at low risk of developing advanced AMD when the subject is homozygous for the T allele at rs1061170 (position 27 of SEQ ID NO: 3); when the subject is homozygous for the A, C or T allele at rs2274700 (position 27 of SEQ ID NO: 4); when the subject is homozygous for the G allele at rs403846 (position 27 of SEQ ID NO: 5); when the subject is homozygous for the A or T allele at rs12144939 (position 27 of SEQ ID NO: 6); when the subject is homozygous for the A allele at rs1409153 (position 27 of SEQ ID NO: 7); when the subject is homozygous for the A allele at rs1750311 (position 27 of SEQ ID NO: 8); when the subject is homozygous for the T allele at rs10922153 (position 27 of SEQ ID NO: 9); when the subject is homozygous for the G allele at rs698859 (position 27 of SEQ ID NO: 10); when the subject is homozygous for the G allele at rs2990510 (position 27 of SEQ ID NO: 11); when the subject is homozygous for the T allele at rs3753394 (position 27 of SEQ ID NO: 12); when the subject is homozygous for the T allele at rs529825 (position 27 of SEQ ID NO: 13); when the subject is homozygous for the C allele at rs800292 (position 27 of SEQ ID NO: 14); when the subject is homozygous for the T allele at rs3766404 (position 27 of SEQ ID NO: 15); when the subject is homozygous for the C allele at rs1061147 (position 27 of SEQ ID NO: 16); when the subject is homozygous for the G allele at rs2033674 (position 27 of SEQ ID NO: 17); when the subject is homozygous for the A allele at rs3753396 (position 27 of SEQ ID NO: 18); or when the subject is homozygous for the G allele at rs1065489 (position 27 of SEQ ID NO: 19). 
     
     
         16 . The method of  claim 1 , wherein the subject's genetic profile is detected by hybridization, chemical cleavage, direct DNA sequencing, use of restriction enzymes or Southern blotting. 
     
     
         17 . The method of  claim 1 , wherein the subject's risk of developing advanced AMD based on their genetic profile for the ARMS2 gene is determined by detecting an insertion/deletion polymorphism starting at position 3143 of SEQ ID NO: 20, wherein the subject is considered at high risk of developing advanced AMD when the subject is homozygous for the insertion/deletion polymorphism, considered at medium risk when the subject is heterozygous for the insertion/deletion polymorphism and is considered at low risk when the subject does not have the insertion/deletion polymorphism, and wherein the insertion/deletion comprises deletion of a nucleic acid sequence from position 3143 of SEQ ID NO: 20 to position 3585 of SEQ ID NO: 20 and insertion of a sequence from position 104 of SEQ ID NO: 21 to position 157 of SEQ ID NO: 21 in place of the deleted sequence. 
     
     
         18 . The method of  claim 1 , wherein subject's risk of developing advanced AMD based on their genetic profile for the ARMS2 gene is determined by analyzing the single nucleotide polymorphism rs10490924 (SEQ ID NO:22) in the ARMS2 gene.