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Nucleic acid sequence related with risperidone clinical curative effect

A technology of nucleic acid sequence and risperidone, applied in the field of nucleic acid sequence in the field of gene technology

Active Publication Date: 2006-12-27
中科基因生物科技(江苏)有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The single nucleotide polymorphism rs1799978 (A-241G) is located in the upstream regulatory region of the DRD2 gene. After searching the existing technical literature, it is found that there is no single nucleotide polymorphism site rs1799978 and Li Pei in the DRD2 gene so far. Related reports on the clinical efficacy of risperidone, which can be used as molecular markers to predict the clinical efficacy of risperidone

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] Example 1: Collection and extraction of genes

[0042] The patients with schizophrenia were from the Shanghai Mental Health Center, China, and the DSM-IV (the second revision of the Chinese psychiatric classification scheme and diagnostic criteria) was used as the diagnostic standard. Under the premise of informed consent, participants participated in the research of this subject, collected blood, and signed an informed consent form. All enrolled patients had no history of second-generation antipsychotic drugs, and the clinical trial began after a drug washout period of 4 weeks. The Brief Psychiatric Rating Scale (BPRS) was used to score the clinical symptoms of the patients at the beginning of the experiment, 4 weeks, and 8 weeks respectively. Those whose BPRS reduction rate was greater than or equal to 40% were defined as effective, and those less than 40% were considered invalid. .

Embodiment 2

[0043] Example 2: Obtaining Nucleotide Sequence and Detection of Single Nucleotide Polymorphism Site rs1799978

[0044]The present invention adopts the method of direct sequencing to detect the DRD2 gene single nucleotide polymorphism site rs1799978 (its allelic site is A / G) allele site in the risperidone treatment effective patient group and the risperidone treatment ineffective patient group The frequency distribution in the group was examined. All PCR reactions were carried out in 96-well plates and completed with Gene Amp PCR system9700.

[0045] (1) PCR reaction

[0046] Amplification primers:

[0047] Forward primer (Pri-F): 5'-CCCCACCAAAGGAGCTGTACCT-3' (SEQ ID NO: 2)

[0048] Reverse primer (Pri-R): 5'-CAGAAAACGGATGCGGACCTCT-3' (SEQ ID NO: 3)

[0049] Reagent:

[0050] The total volume of the reaction system is 10.0ul, where

[0051] ddH2O 5.8ul sterile double distilled water

[0052] Buffer 1.0ul polymerization reaction buffer contains Mg2+ Tris-HCl solution

...

Embodiment 3

[0070] Example 3: Correlation between single nucleotide polymorphism site rs1799978 and clinical efficacy of risperidone

[0071] Statistics: Use SPSS10.0 to calculate the distribution of alleles, genotypes and Hardy-Weinberg balance, and calculate Odds Ratio (OR) and its 95% credible interval, and use G Power Program to calculate the statistical power of the sample size used , the chi-square test was used for statistical analysis, and the statistical significance level was set at P less than 0.05.

[0072] Results: The frequency distribution of rs1799978 (its allele is A / G) allele located in the upstream regulatory region of DRD2 gene in the 11q22-23 region in the risperidone treatment effective group and the risperidone treatment ineffective patient group See Table 1.

[0073] group

Number of samples

Genotype (Frequency%)

Number of alleles (frequency%)

invalid group

effective group

P

OR (95%CI)

53

72

AA ...

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PUM

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Abstract

The invention relates to a nucleic acid sequence correlative with Risperidone clinical curative effect in gene technical sphere. The separated DNA molecule by this invention has sequence indicated in SEQ ID NO:1 and the 251th order of the indicated sequence in SEQ ID NO: 1 is mononucleotide polymorphism site rs1799978, in which the said mononucleotide polymorphism site rs1799978 names that the 251th order of the indicated sequence in SEQ ID NO: 1 exists A, the said DNA of complementary chain is T equipotential site and lies in 241th order of DRD2 gene upstream. The 251th order of the indicated sequence in SEQ ID NO: 1 is mononucleotide polymorphism site is A homozygote. Using this invention to predict Risperidone clinical curative effect does not depend on medical subjective techniques and statute of limitation is strong, and consequently is a potential tool which can be aided by clinical just drugs.

Description

technical field [0001] The present invention relates to a nucleic acid sequence in the field of gene technology, in particular to a nucleic acid sequence related to the clinical curative effect of risperidone. Background technique [0002] Risperidone (risperidone) is a new generation of antipsychotic drugs, developed by the Belgian Janssen Pharmaceutical Company in 1984, the trade name is Risperidal (Risperidal), which is a benzisoxazole (benzisoxazole) derivative, it is 5-HT2 receptor Compared with the first-generation antipsychotic drugs, risperidone has good curative effect on positive symptoms and negative symptoms of schizophrenia, and has adverse effects such as extrapyramidal symptoms (EPS). Low incidence of reactions (Leysen JE, Gommeren W, Eens A, De Chaffog De Coucelles D, Stoof JC, Janssen PAJ. Biochemical profile of risperidone, a new antipsychotic. J Pharmacol Exp Ther 1988; 247:661-670). In practical application, there are great individual differences in the ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/12A61K48/00A61P25/00
Inventor 贺林邢清和秦炜高建军钱学庆李华芳
Owner 中科基因生物科技(江苏)有限公司
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