Method for evaluating urate transport-related disease factor and inflammation-related disease factor

Abstract

A method and evaluation kit are provided, in which a high-capacity urate transporter is identified to assist in the early treatment and prevention of urate transport-related disease and inflammation-related disease. The method can include a step for detecting variations in genes that encode ABCG2 protein. When a subject has an SNP of V12M, R113X, Q126X, Q141K, F2085, 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 evaluating urate transport-related disease factor and inflammation-related disease factor, the method comprising:
 evaluating whether or not a subject has a factor that induces urate transport failure, or a state or a disease attributable to that failure, the method of evaluating including detecting variations in genes that encode an ABCG2 protein using a sample containing human genes of the subject.   
     
     
         2 . The method for evaluating urate transport-related disease factor and inflammation-related disease factor of  claim 1 , wherein the detecting of variations in genes that encode an ABCG2 protein includes detecting an SNP or a gene polymorphism having a relationship of linkage disequilibrium with the SNP. 
     
     
         3 . The method for evaluating urate transport-related disease factor and inflammation-related disease factor of  claim 2 , wherein the detecting of the gene polymorphism 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 for evaluating urate transport-related disease factor and inflammation-related disease factor of  claim 1 , wherein the detecting includes identifying an SNP producing at least one amino acid variation of a component selected from the group consisting of V12M, R113X, Q126X, Q141K, F208S, G268R, E334X, S441N, L447V, S486N, F506SfsX4, R575X, and C608X as a factor in the inducement of urate transport failure, or a state or a disease attributable to that failure. 
     
     
         5 . The method for evaluating urate transport-related disease factor and inflammation-related disease factor of  claim 4 , wherein the detecting includes identifying an SNP producing either amino acid variation of Q126X alone or a combination of Q126X and Q141K as a factor in the inducement of urate transport failure, or a state or a disease attributable to that failure. 
     
     
         6 . The method for evaluating urate transport-related disease factor and inflammation-related disease factor of  claim 1 , wherein the detecting includes identifying a functional change of ABCG2 including a functional failure thereof, as a factor in the inducement of urate transport failure, or a state or a disease attributable to that failure. 
     
     
         7 . The method for evaluating urate transport-related disease factor and inflammation-related disease factor of  claim 6 , wherein the functional change of ABCG2, including a functional failure thereof, comprises any one of
 a functional change of ABCG2 by a gene variation other than the amino acid variations of an SNP producing at least one amino acid variation of a component selected from the group consisting of V12M, R113X, Q126X, Q141K, F208S, G268R, E334X, S441N, L447V, S486N, F506SfsX4, R575X, and C608X,   a functional change of ABCG2 based on a change of an expression amount by a gene variation in exons or introns containing a promoter and an untranslated region (UTR) of ABCG2,   a functional change of ABCG2 by a change of a control factor including a transcription factor, or a compound,   a functional change of ABCG2 by a copy number variant (CNV),   an epigenetic change including DNA methylation, a functional change of ABCG2 by an RNA including a micro RNA or a noncoding RNA, and   a functional change of ABCG2 by a change of a stabilization mechanism of the ABCG2 protein.   
     
     
         8 . The method for evaluating urate transport-related disease factor and inflammation-related disease factor of  claim 1 , wherein the detecting includes identifying a serum uric acid level as a state or a disease attributable to urate transport failure. 
     
     
         9 . The method for evaluating urate transport-related disease factor and inflammation-related disease factor of  claim 8 , wherein the serum uric acid level ranges between 6.0 and 9.0 mg/dl. 
     
     
         10 . The method for evaluating urate transport-related disease factor and inflammation-related disease factor of  claim 8 , wherein the serum uric acid level ranges between 7.0 and 8.0 mg/dl. 
     
     
         11 . The method for evaluating urate transport-related disease factor and inflammation-related disease factor of  claim 1 , the urate transport failure, or state or a disease attributable to that failure, includes 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. 
     
     
         12 . The method for evaluating urate transport-related disease factor and inflammation-related disease factor of  claim 1 , wherein the urate transport failure, or state or a disease attributable to that failure, includes hyperuricemia, gout, rheumatoid arthritis, osteoarthritis, infertility, cerebral stroke, an ischemic heart disease, arrhythmia, photosensitivity, and a chronic kidney disease.