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 identifying an individual who has an altered risk for developing psoriasis, comprising detecting at least one single nucleotide polymorphism (SNP) in any one of the nucleotide sequences of SEQ ID NOS:7-12 and 24-89 in said individual's nucleic acids, wherein the presence of the SNP is indicative of an altered risk for psoriasis in said individual. 
     
     
         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 the SNPs set forth in Tables 1-7 and 9-21. 
     
     
         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 . 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:4-6 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. 
     
     
         7 . The method of  claim 1 , wherein the SNP comprises a SNP haplotype selected from the group consisting of:
 the risk haplotype of rs3212227(A) and rs6887695(G);   the protective haplotype of rs3212227(C) and rs6887695(C); and   the risk haplotype of rs11209026(G) and rs 7530511(C).   
     
     
         8 . The method of  claim 1 , wherein the SNP comprises a SNP diplotype selected from the group consisting of:
 two copies of the risk haplotype rs3212227(A) and rs6887695(G);   two copies of the protective haplotype rs3212227(C) and rs6887695(C); and   two copies of the risk haplotype rs11209026(G) and rs 7530511(C).   
     
     
         9 . The method of  claim 2 , wherein the SNP comprises the two-locus diplotype of rs3212227(A), rs6887695(G), rs11209026(G), and rs 7530511(C). 
     
     
         10 . The method of  claim 1 , wherein the SNP comprises a haplotype, diplotype, two-locus diplotype, or 3-SNP combination selected from the group consisting of:
 the haplotypes provided in Tables 12, 13, 15, and 20;   the diplotypes provided in Tables 16 and 17;   two-locus diplotypes provided in Table 18; and   the 3-SNP combinations provided in Table 21.   
     
     
         11 . A method for identifying a human who has an altered risk for developing psoriasis, the method comprising detecting a SNP haplotype selected from the group consisting of the risk haplotype of rs3212227(A) and rs6887695(G); the protective haplotype of rs3212227(C) and rs6887695(C); and the risk haplotype of rs11209026(G) and rs 7530511(C) in said human's nucleic acids, wherein the presence of the SNP haplotype is indicative of an altered risk for psoriasis in said human. 
     
     
         12 . A method for determining whether a human will likely benefit from a drug treatment targeting IL12 or IL23, the method comprising detecting the presence of a SNP in a nucleotide sequence selected from the group consisting of SEQ ID NOS:7-12 and 24-89 in said human's nucleic acids, wherein the presence of the SNP indicates that said human is likely to benefit from the drug treatment. 
     
     
         13 . The method of  claim 12 , wherein the human is selected for inclusion in a clinical trial of the drug treatment. 
     
     
         14 . A method of treating a human who will likely benefit from a drug treatment targeting IL12 or IL23, the method comprising detecting the presence of a SNP in a nucleotide sequence selected from the group consisting of SEQ ID NOS:7-12 and 24-89 in said human's nucleic acids, wherein the presence of the SNP indicates that said human is likely to benefit from the drug treatment, and administering said drug treatment to said human.