Genetic polymorphisms associated with psoriasis, methods of detection and uses thereof

Abstract

The present invention is based on the discovery of genetic polymorphisms that are associated with psoriasis and related pathologies. In particular, the present invention relates to nucleic acid molecules containing the polymorphisms, including groups of nucleic acid molecules that may be used as a signature marker set, such as a haplotype, a diplotype, variant proteins encoded by such nucleic acid molecules, reagents for detecting the polymorphic nucleic acid molecules and proteins, and methods of using the nucleic acid and proteins as well as methods of using reagents for their detection.

1 . A method for determining whether a human has an altered risk for psoriasis or Crohn's Disease, comprising testing nucleic acid from said human for the presence or absence of a single nucleotide polymorphism (SNP) as represented by position 101 of SEQ ID NOS: 5-9 and 19-110 or their complements, wherein the presence of the SNP indicates said human has an altered risk for psoriasis or Crohn's Disease. 
     
     
         2 . The method of  claim 1  in which the altered risk is an increased risk. 
     
     
         3 . The method of  claim 1  in which the altered risk is a decreased risk. 
     
     
         4 . The method of  claim 1 , wherein the SNP is selected from the group consisting of rs1800925, rs20541, and rs848. 
     
     
         5 . The method of  claim 1  in which detection is carried out by a process selected from the group consisting of: allele-specific probe hybridization, allele-specific primer extension, allele-specific amplification, sequencing, 5′ nuclease digestion, molecular beacon assay, oligonucleotide ligation assay, size analysis, and single-stranded conformation polymorphism. 
     
     
         6 . The method of  claim 1 , wherein said nucleic acid is a nucleic acid extract from a biological sample from said human. 
     
     
         7 . The method of  claim 1 , wherein said biological sample is blood, saliva, or buccal cells. 
     
     
         8 . The method of  claim 1 , further comprising preparing said nucleic acid extract from said biological sample prior to said testing step. 
     
     
         9 . The method of  claim 8 , further comprising obtaining said biological sample from said human prior to said preparing step. 
     
     
         10 . The method of  claim 1 , wherein said testing step comprises nucleic acid amplification. 
     
     
         11 . The method of  claim 10 , wherein said nucleic acid amplification is carried out by polymerase chain reaction. 
     
     
         12 . The method of  claim 1 , further comprising correlating the presence or absence of said SNP with the altered risk for psoriasis or Crohn's Disease. 
     
     
         13 . The method of  claim 1 , wherein said correlating step is performed by computer software. 
     
     
         14 . A method for identifying an agent useful in therapeutically or prophylactically treating psoriasis, the method comprising contacting a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NOS: 3-4 with a candidate agent under conditions suitable to allow formation of a binding complex between the polypeptide and the candidate agent, and detecting the formation of the binding complex, wherein the presence of the complex identifies said agent. 
     
     
         15 . The method of  claim 1 , wherein the SNP comprises a SNP haplotype selected from the group consisting of: the risk haplotype of rs1800925(C), rs20541(C), and rs848(G); and the protective haplotype of rs1800925(T), rs20541(T), and rs848(T). 
     
     
         16 . The method of  claim 2 , wherein the SNP comprises the risk haplotype of rs1800925(C), rs20541(C), and rs848(G). 
     
     
         17 . The method of  claim 3 , wherein the SNP comprises the protective haplotype of rs1800925(T), rs20541(T), and rs848(T). 
     
     
         18 . A method for determining a human's risk of developing psoriasis, the method comprising detecting a SNP haplotype selected from the group consisting of the risk haplotype of rs1800925(C), rs20541(C), and rs848(G) and the protective haplotype of rs1800925(T), rs20541(T), and rs848(T) in said human's nucleic acids, wherein the presence of the SNP haplotype is indicative of an altered risk of developing psoriasis in said human. 
     
     
         19 . A method for determining whether a human will likely benefit from a drug treatment targeting IL13, the method comprising testing nucleic acid from said human for the presence or absence of a SNP as represented by position 101 of SEQ ID NOS: 5-9 and 19-110 or their complement, wherein the presence or absence of the SNP indicates that said human is likely to benefit from the drug treatment. 
     
     
         20 . The method of  claim 19 , wherein the human is selected for inclusion in a clinical trial of the drug treatment. 
     
     
         21 . A method of treating a human who will likely benefit from a drug treatment targeting IL13, the method comprising testing nucleic acid from said human for the presence or absence of a SNP as represented by position 101 of SEQ ID NOS: 5-9 and 19-110 or their complement, wherein the presence or absence of the SNP indicates that said human is likely to benefit from the drug treatment, and administering said drug treatment to said human. 
     
     
         22 . The method of any one of  claim 4 ,  15 , or  18 , wherein the method further comprises detecting at least one variant selected from the group consisting of HLA-C, SNPs in IL12B, and SNPs in IL23R. 
     
     
         23 . The method of  claim 22 , wherein the HLA-C variant is HLA-C *0602. 
     
     
         24 . The method of  claim 22 , wherein the SNPs in IL12 and IL23R are selected from the group consisting of:
 SNPs rs321227, rs3212220, rs7709212, and rs6887695;   the psoriasis risk haplotype rs3212227(A)/rs6887695(G);   the psoriasis protective haplotype rs3212227(C)/rs6887695(C);   the psoriasis risk haplotype rs11209026(G)/rs7530511(C);   a SNP diplotype which is a combination of two copies of the risk haplotype, rs3212227(A)/rs6887695(G);   a SNP diplotype which is a combination of two copies of the protective haplotype, rs3212227(C)/rs6887695(C);   a SNP diplotype which is a combination of two copies of the risk haplotype rs11209026(G)/rs 7530511(C); and   a two-locus diplotype which is a combination of rs3212227(A)/rs6887695(G)/rs11209026(G)/rs7530511(C).   
     
     
         25 . A kit for carrying out the method of  claim 1 , wherein the kit comprises at least one polynucleotide detection reagent, and wherein the polynucleotide detection reagent selectively hybridizes to said nucleic acid in the presence of said polymorphism and does not hybridize to said nucleic acid in the absence of said polymorphism.