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Method for evaluating drug sensitivity and disease vulnerability by analyzing cyclic amp responsive element binding protein gene

a technology of cyclic amp responsive element and gene, applied in the field of method for evaluating drug sensitivity and disease vulnerability, can solve the problems of significantly reducing qol (quality of life) by excessive pain, and achieve the effect of knowing or predicting

Inactive Publication Date: 2017-12-14
TOKYO METROPOLITAN INST OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present patent is about a gene called cyclic AMP responsive element binding protein (CREB) and its polymorphisms. The inventors studied the gene and discovered that certain polymorphisms were associated with different responses to drugs like pain medication and disease vulnerability. They also found that these polymorphisms were linked together, which makes it easier to predict how an individual will respond to medication. This gene polymorphism can be used to determine the best way to prescribe drugs for pain and drug dependence treatment.

Problems solved by technology

The pain sensation plays an important role in terms of a biological warning system, however, excessive pain would significantly decrease QOL (quality of life) unless it is properly controlled.

Method used

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  • Method for evaluating drug sensitivity and disease vulnerability by analyzing cyclic amp responsive element binding protein gene
  • Method for evaluating drug sensitivity and disease vulnerability by analyzing cyclic amp responsive element binding protein gene
  • Method for evaluating drug sensitivity and disease vulnerability by analyzing cyclic amp responsive element binding protein gene

Examples

Experimental program
Comparison scheme
Effect test

example 1

(SNP Analysis)

[0110]Genomic DNA was extracted from the blood of humans (127 Japanese healthy subjects) by a standard method, and gene polymorphisms were identified in four subtypes (CREB1, CREB3, CREB5, and ATF2) of a human cyclic AMP responsive element binding protein.

[0111]With regard to the CREB1 subtype gene, an entire exon region, 5′ and 3′ flanking regions, and an intron region were analyzed. In the case of the CREB1 subtype gene, 7 gene polymorphisms in an intron region were identified in the Japanese samples. Further, 4 and 6 gene polymorphisms were found in the 5′ and 3′ flanking regions, respectively (see Table 15). As a result of linkage disequilibrium analysis, 1 linkage disequilibrium block was found in a region ranging from the 5′ flanking region to the 3′ flanking region (see FIG. 1 and FIG. 2). It was found that rs16839837, rs2360969, rs10932200, rs2551946, rs4234080 and rs7594560 were suitable as Tag SNPs representing this linkage disequilibrium block.

[0112]Further,...

example 2

[0130]

[0131]A correlation between a cyclic AMP responsive element binding protein gene polymorphism and the required administration amount of analgesic was examined. Genomic DNA was extracted from the blood of 247 patients undergoing surgery (orthognathic surgery), and one gene polymorphism (rs10932200) in the CREB1 subtype gene was determined. Then, a correlation between these results of determination of the gene polymorphism and the required administration amount of analgesic after the surgery was analyzed.

[0132]Incidentally, as the analgesic, fentanyl, which is mainly administered intravenously through a PCA (patient-controlled analgesia) pump, was used.

[0133]As a result, as shown in the following Table 21 and FIG. 9, in the case of patients who had a minor allele (C) of the CREB1 subtype gene polymorphism (rs10932200) and underwent the surgery, the required administration amount (logarithmic transformation) of analgesic after the surgery was statistically significantly high in c...

example 3

[0135]

[0136]A correlation between a cyclic AMP responsive element binding protein gene polymorphism and pain sensitivity was examined. Genomic DNA was extracted from the blood of 247 patients undergoing surgery (orthognathic surgery), and one gene polymorphism (rs10932200) in the CREB1 subtype gene was determined. Then, a correlation between these results of determination of the gene polymorphism and the measurement of pain perception latency due to finger immersion in ice water before the surgery was analyzed.

[0137]As a result, as shown in the following Table 22 and FIG. 10, in the case of patients who had a minor allele (C) of the CREB1 subtype gene polymorphism (rs10932200) and underwent the surgery, the measurement result (logarithmic transformation) of pain perception latency was statistically significantly low in correlation with the number of alleles which they had. Accordingly, by analyzing the CREB1 subtype gene polymorphism (rs10932200), the sensitivity to pain can be pred...

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Abstract

The present invention provides a method for evaluating (predicting, etc.) an individual difference (the tendency of every individual) in terms of drug sensitivity and disease vulnerability, comprising using a gene polymorphism of a cyclic AMP responsive element binding protein gene or the like. The method for evaluating drug sensitivity and the method for evaluating disease vulnerability according to the present invention comprise associating a gene polymorphism of a cyclic AMP responsive element binding protein gene or a haplotype constituted by the gene polymorphism with the drug sensitivity and disease vulnerability of an individual.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a Continuation of copending application Ser. No. 14 / 347,500, filed on Mar. 26, 2014, which is the National Phase under 35 U.S.C. §371 of PCT International Application No. PCT / JP2012 / 076054, filed on Oct. 1, 2012, which claims priority under 35 U.S.C. §119(a) to Patent Application No. 2011-217104, filed in JAPAN on Sep. 30, 2011, all of which are hereby expressly incorporated by reference into the present application.TECHNICAL FIELD[0002]The present invention relates to a method for evaluating drug sensitivity and disease vulnerability, comprising analyzing a cyclic AMP responsive element binding protein (cAMP responsive element binding protein; CREB) gene. Specifically, the present invention relates to a method for evaluating drug sensitivity and disease vulnerability, comprising associating a gene polymorphism of a CREB gene or a haplotype constituted by the gene polymorphism with the drug sensitivity and disease vuln...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): G06F19/18C12Q1/68G16B20/20
CPCG06F19/18C12Q2600/156C12Q2600/106C12Q1/6883G16B20/00G16B20/20
Inventor IKEDA, KAZUTAKANISHIZAWA, DAISUKEFUKUDA, KENICHI
Owner TOKYO METROPOLITAN INST OF MEDICAL SCI