Identification of genetic variants

Abstract

The present disclosure provides a method for identifying whether a subject is more or less likely to be responsive to VEGF-based therapy, comprising screening a nucleic acid sample obtained from the subject to provide output information which identifies the presence or absence of an allelic variant, wherein the presence or absence of an allelic variant indicates whether the subject is more or less likely to be responsive to VEGF-based therapy.

1 . A method for identifying whether a subject is more or less likely to be responsive to VEGF-based therapy, comprising screening a nucleic acid sample obtained from the subject to provide output information which identifies the presence or absence of an allelic variant, wherein the allelic variant is selected from the group consisting of:
 i. rs6921438   ii. rs4416670   iii. rs6993770   iv. rs10738760   wherein the presence or absence of an allelic variant indicates whether the subject is more or less likely to be responsive to VEGF-based therapy,   wherein if the nucleic acid sample is screened for the allelic variant rs6921438, a guanine residue at base 323 of SEQ ID No. 1 at one or both alleles indicates that the subject is more likely to be responsive to VEGF-based therapy,   wherein if the nucleic acid sample is screened for the allelic variant rs4416670, a thymine residue at base 221 of SEQ ID No. 2 at one or both alleles indicates that the subject is more likely to be responsive to VEGF-based therapy,   wherein if the nucleic acid sample is screened for the allelic variant rs6993770, a thymine residue at base 235 of SEQ ID No. 3 at one or both alleles indicates that the subject is less likely to be responsive to VEGF-based therapy, and/or   wherein if the nucleic acid sample is screened for the allelic variant rs10738760, a guanine residue at base 201 of SEQ ID No. 4 at one or both alleles indicates that the subject is more likely to be responsive to VEGF-based therapy.   
     
     
         2 . A method according to  claim 1 , wherein the method comprises screening for at least two of the allelic variants (i)-(iv). 
     
     
         3 . A method according to  claim 1 , wherein the VEGF-based therapy is anti-VEGF therapy. 
     
     
         4 . A method according to  claim 3 , wherein the anti-VEGF therapy is a drug selected from bevacizumab, ranibizumab, lapatinib, sunitinib (Sutent™), sorafenib, axitinib, pazopanib and thiazolidinediones. 
     
     
         5 . A method for identifying whether a subject is more or less likely to be responsive to VEGF-based therapy, comprising screening a nucleic acid sample obtained from the subject to provide output information which identifies the presence or absence of at least one allelic variant associated with VEGF mRNA,
 wherein the at least one allelic variant is selected from the group consisting of:
 v. rs16873365 (base 251 of SEQ ID NO. 5) 
 vi. rs16873402 (base 251 of SEQ ID NO. 6) 
 vii. rs6993770 (base 235 of SEQ ID NO. 3) 
 viii. rs16873291 (base 251 of SEQ ID NO. 7) 
 ix. rs2375980 (base 501 of SEQ ID NO. 8) 
 x. rs910611 (base 301 of SEQ ID NO. 9) 
   and wherein the presence or absence of an allelic variant at one or both alleles indicates that the subject is more or less likely to be responsive to VEGF-based therapy.   
     
     
         6 . A method for identifying whether a subject is more or less likely to be responsive to VEGF-based therapy, comprising:
 (i) screening a sample obtained from the subject to determine the level of expression of one or more of the VLDLR, LRP12, ZFPM2 and KCNV2 genes; and   (ii) comparing against a control value,   wherein an increase in expression compared to the control indicates that the subject is more or less likely to be responsive to VEGF-based therapy.   
     
     
         7 . A method for identifying molecules that affect the level of circulating VEGF in a subject, comprising screening a target molecule to provide output information to establish whether the molecule affects the activity of the product of any of the VLDLR, LRP12, ZFPM2 and KCNV2 genes, wherein a molecule that inhibits the activity will alter the level of circulating VEGF in vivo. 
     
     
         8 . A method for administering a VEGF-based therapy to a subject, the method comprising the step of screening a nucleic acid sample obtained from the subject to provide output information which identifies the presence or absence of an allelic variant,
 wherein the allelic variant is selected from the group consisting of:
 xi. rs6921438 
 xii. rs4416670 
 xiii. rs6993770 
 xiv. rs10738760 
   wherein if the nucleic acid sample is screened for the allelic variant rs6921438 and a guanine residue is detected at base 323 of SEQ ID No. 1 at one or both alleles, a VEGF-based therapy is administered,   wherein if the nucleic acid sample is screened for the allelic variant rs4416670 and a thymine residue is detected at base 221 of SEQ ID No. 2 at one or both alleles, a VEGF-based therapy is administered,   wherein if the nucleic acid sample is screened for the allelic variant rs6993770 and a thymine residue is detected at base 235 of SEQ ID No. 3 at one or both alleles, a VEGF-based therapy is not administered,   wherein if the nucleic acid sample is screened for the allelic variant rs10738760 and a guanine residue is detected at base 201 of SEQ ID No. 4 at one or both alleles, a VEGF-based therapy is administered.   
     
     
         9 . A method according to  claim 8 , wherein the VEGF-based therapy is an anti-VEGF drug selected from bevacizumab, ranibizumab, lapatinib, sunitinib (Sutent™), sorafenib, axitinib, pazopanib and thiazolidinediones. 
     
     
         10 . A solid support substrate having an array of affinity molecules deposited thereon, wherein the molecules have affinity for and/or hybridize to, one or more polynucleotides comprising single nucleotide polymorphisms identified herein as rs6921438, rs4416670, rs6993770, rs10738760, rs16873365, rs16873402, rs16873291, rs2375980, rs910611 and/or wherein the molecules have affinity for and/or hybridize to one or more of the genes selected from VLDLR, LRP12, ZFPM2 and KCNV2. 
     
     
         11 . A solid support substrate according to  claim 10 , wherein the molecules are polynucleotides. 
     
     
         12 . A solid support substrate according to  claim 10 , wherein the molecules are covalently attached to the substrate.