Fibrosis susceptibility il22ra2 gene and uses thereof

Abstract

The present invention discloses the identification of a fibrosis susceptibility gene locus, the IL22RA2 gene locus, which can be used for detecting predisposition to, diagnosis and prognosis of fibrosis as well as for the screening of therapeutically active drugs. The invention further provides a method for determining the likelyhood of a patient affected with a viral infection to respond to a treatment with an antiviral agent and/or an interferon, which method comprises determining alteration in IL22RA2 gene locus or in TL22RA2 expression or IL22RA2 protein activity in a biological sample of the patient.

1 - 30 . (canceled) 
     
     
         31 . A non-invasive method of preventing or reducing the progression of fibrosis, comprising:
 a) obtaining a biological sample from a human subject, wherein the human subject has been infected with a hepatic virus or a parasite;   b) detecting in the biological sample obtained from the subject with an assay a single nucleotide polymorphism at a IL22RA2 gene locus, wherein the single nucleotide polymorphism comprises rs6570136 having a genotype of GG or AG; and   c) treating the human subject with an anti-fibrotic therapy.   
     
     
         32 . The method of claim  30 , wherein the human subject self-identifies as being Chinese, Brazilian, or Sudanese. 
     
     
         33 . The method of claim  30 , wherein the hepatic virus is hepatic C virus. 
     
     
         34 . The method of claim  30 , wherein the biological sample comprises saliva or blood. 
     
     
         35 . The method of claim  30 , wherein the assay comprises selective hybridization or sequencing of at least a portion of the IL22RA2 gene locus containing the single nucleotide polymorphism. 
     
     
         36 . The method of claim  30 , wherein the parasite is a  Schistosoma  parasite. 
     
     
         37 . The method of claim  30 , further comprising detecting in a biological sample obtained from the subject, an additional single nucleotide polymorphism at the IL22RA2 gene locus, wherein the additional single nucleotide polymorphism comprises rs7774663 having a genotype of C, CC, and/or TT. 
     
     
         38 . The method of claim  30 , further comprising detecting in a biological sample obtained from the subject at least two additional single nucleotide polymorphisms at the IL22RA2 gene locus, wherein the at least two additional single nucleotide polymorphisms comprise rs7774663 having a genotype of CC or TT, and rs2064501 having a genotype of TT. 
     
     
         39 . The method of claim  30 , wherein the assay comprises microsequencing of at least a portion of the IL22RA2 gene locus containing the single nucleotide polymorphism. 
     
     
         40 . The method of claim  30 , wherein the assay comprises an allele-specific amplification of at least a portion of the IL22RA2 gene locus containing the single nucleotide polymorphism. 
     
     
         41 . The method of claim  30 , wherein the single nucleotide polymorphism is associated with a risk that a subject will develop abnormal deposit of extracellular matrix components. 
     
     
         42 . The method of claim  30 , wherein the fibrosis is hepatic fibrosis. 
     
     
         43 . A method of treating fibrosis in a human subject comprising administering to the subject a therapeutically effective amount of an anti-fibrotic therapy, provided one or more single nucleotide polymorphisms at a IL22RA2 gene locus comprising rs6570136 having a genotype of GG or AG is detected in a biological sample obtained from the subject. 
     
     
         44 . The method of  claim 43 , wherein the subject has been infected with a hepatic virus or a parasite. 
     
     
         45 . The method of  claim 43 , wherein the human subject self-identifies as being Chinese, Brazilian, or Sudanese. 
     
     
         46 . The method of  claim 43 , wherein the hepatic virus is hepatic C virus. 
     
     
         47 . The method of  claim 43 , wherein the biological sample comprises saliva or blood. 
     
     
         48 . The method of  claim 43 , wherein the one or more single nucleotide polymorphisms at the IL22RA2 gene locus further comprises rs7774663 having a genotype of C, CC, and/or TT. 
     
     
         49 . The method of  claim 43 , wherein the one or more single nucleotide polymorphisms at the IL22RA2 gene locus further comprises rs7774663 having a genotype of CC or TT, and rs2064501 having a genotype of TT. 
     
     
         50 . A method of preventing or reducing fibrosis in a human subject, the method comprising:
 determining whether the subject is at risk for developing abnormal deposit of extracellular matrix components by:   (i) obtaining a biological sample from the subject; and   (ii) performing a genotyping assay on the biological sample to determine if the subject has a rs6570136GG or a rs6570136AG genotype; and   if the subject has the rs6570136GG or the rs6570136AG genotype, then administering to the subject an anti-fibrotic therapy, and   if the subject does not have the rs6570136GG or the rs6570136AG genotype, then administering to the subject a therapy other than the anti-fibrotic therapy.