Method of treating, or at least inhibiting the onset of, urate transport failure

Abstract

Methods of treating, or at least inhibiting the onset of, urate transport failure are provided. The methods can include a step for detecting variations in genes that encode ABCG2 protein. When a subject has an SNP of V12M, R113X, Q126X, Q141K, F208S, G268R, E334X, S441N, L447V, S486N, F506SfsX4, R575X, and/or C608X, it can be concluded that the subject has a factor that is capable of inducing urate transport failure, or a state or disease attributable to that failure. When a subject has an SNP of V12M, it can be concluded that, unlike the other SNPs, there is a possibility that the subject does not possess such a factor because, although this variation itself does not lead to a change in urate transport capability, said variation is related to linkage disequilibrium with other SNPs.

We claim: 
     
         1 . A method for treating, or at least inhibiting the onset of, urate transport failure in a human subject, the method comprising:
 providing a tissue sample from the human subject for use in detecting one or more ABCG2 gene variations in the tissue sample; wherein, the one or more gene variations includes a SNP producing an amino acid variation in the tissue sample selected from the group consisting of V12M, R113X, Q126X, Q141K, F208S, G268R, E334X, S441N, L447V, S486N, F506SfsX4, R575X, and C608X as a genetic factor capable of inducing the urate transport failure;   obtaining results from the detecting; and,   administering a urate transporter to the subject, the urate transporter comprising a polypeptide having an amino acid sequence of SEQ ID NO:62;   wherein, the administering effectively treats, or at least inhibits the onset of, urate transport failure in the human subject.   
     
     
         2 . The method of  claim 1 , wherein the one or more gene variations includes combination of SNPs in linkage disequilibrium. 
     
     
         3 . The method of  claim 1  wherein the detecting includes using a detection method selected from the group consisting of a direct sequencing method, a BAC array CGH method, a FISH method, an RFLP method, a PCR-SSCP method, an allele-specific oligonucleotide hybridization method, a TaqMan PCR method, an invader method, an HRM method, a SmartAmp method, a Q-probe method (QP method), a MALDI-TOF/MS method, a molecular beacon method, an RCA method, a UCAN method, and a nucleic acid hybridization method using a DNA chip or a DNA microarray. 
     
     
         4 . The method of  claim 1 , wherein the SNP is Q126X. 
     
     
         5 . The method of  claim 2 , wherein the combination of SNPs is Q126X in combination with Q141K. 
     
     
         6 . A method of treating, or at least inhibiting the onset of, urate transport failure, the method comprising:
 obtaining a tissue sample from a test subject for identifying a functional change in ABCG2 genes in the tissue sample; and,   identifying a functional change in the ABCG2 genes in the tissue sample from the test subject when compared to the ABCG2 genes in a tissue sample from a wild-type subject, the functional change selected from the group consisting of
 a lower amount of ABCG2 protein expression from the tissue sample of the test subject when compared to a corresponding amount of ABCG2 protein expression from the tissue sample from the wild-type subject; 
 a change of a transcription factor for the ABCG2 genes from the tissue sample of the test subject when compared to a corresponding transcription factor for the ABCG2 genes from the tissue sample from the wild-type subject; 
 a change in copy number variation (CNV) of the ABCG2 genes from the tissue sample of the test subject when compared to a corresponding CNV of the ABCG2 genes from the tissue sample from the wild-type subject; and/or 
 an increased amount of DNA methylation of the ABCG2 genes from the tissue sample of the test subject when compared to a corresponding DNA methylation of the ABCG2 genes from the tissue sample from the wild-type subject; 
   and,   administering a urate transporter to the subject, the urate transporter comprising a polypeptide having an amino acid sequence of SEQ ID NO:62;   wherein, the administering effectively treats, or at least inhibits the onset of, urate transport failure in the human subject.   
     
     
         7 . The method of  claim 1 , further comprising identifying a threshold serum uric acid level of at least 7.0 mg/dl. 
     
     
         8 . The method of  claim 1 , further comprising identifying a serum uric acid level that ranges between 6.0 and 9.0 mg/dl. 
     
     
         9 . The method of  claim 1 , further comprising identifying a serum uric acid level that ranges between 7.0 and 8.0 mg/dl. 
     
     
         10 . The method of  claim 1 , further comprising attributing the urate transport failure to a hyperuricemia selected from a group consisting of a uric acid overproduction type, an extrarenal uric acid underexcretion type, a renal uric acid underexcretion type, and a mixed type thereof. 
     
     
         11 . The method of  claim 1 , further comprising attributing the urate transport failure to hyperuricemia, gout, rheumatoid arthritis, osteoarthritis, infertility, cerebral stroke, an ischemic heart disease, arrhythmia, photosensitivity, and a chronic kidney disease.