SNP Study of DPP-4 and GLP-1R in Chinese People (Including Diabetes Patients)
Condition: Diabetes Mellitus
MeSH terms: Diabetes Mellitus
Study type: Interventional
Phase: Phase 4

Summary: 
      Incretin-based therapy is currently one of the most popular diabetes treatment approaches.
      However, differences of response ware found in previous studies. We hypothesis that SNPs of
      DPP-4, GLP-1 and GLP-1R genes may play crucial roles in the response differences. Therefore,
      this study aims to investigate the correlation of incretin-related gene polymorphism and
      individual differences in the response of DPP-4 inhibators (take Sitagliptin as an example).
      In addition, The distribution differences of the SNPs in diabetics and non-diabetics are
      evaluated to study the relationships between the SNPs and diabetes onsets.
    

Detailed description: 
      Single Nucleotide Polymorphism (SNP) plays an important role in the differences of clinical
      manifestations and drug responses of diseases. The vast majority of SNP sites are located in
      the non-coding region of the gene (about 95%), which is called SNP(non-coding SNP (ncSNP),
      while the other part of SNP is located in the coding region of the gene, which is called
      coding SNP (cSNP). Furthermore, cSNP can be divided into two categories: SNP that does not
      change the encoded amino acid sequence is called synonymous SNP(synonymous SNP, SSNP); SNP
      that changes amino acid sequence is called SNP(non-synonymous SNP (NSNP). Although not
      involved in coding amino acid, some ncSNPs may also affect the regulation of protein
      expression. Therefore, it is of great significance to study the effects of NC SNP and cSNP on
      the occurrence and development of diseases and drugs.

      DPP-4 enzyme inhibitor is combined with DPP-4 enzyme in human body to reduce hydrolysis of
      active GLP-1, thus increasing the level of endogenous active GLP-1. Active GLP-1 combines
      with its receptor GLP-1R to promote insulin release and inhibit glucagon release in
      hyperglycemia state, and produces opposite effect in hypoglycemia state.

      Based on the above principles, we speculate that SNP of genes that may affect the
      hypoglycemic effect of DPP-4 enzyme inhibitor are:

        1. SNP of DPP-4 enzyme gene. SNP of DPP-4 enzyme gene may affect the enzyme activity and/or
           protein expression level of DPP-4. Assuming that the effect of DPP-4 enzyme inhibitor is
           sufficient, patients with higher DPP-4 enzyme activity are more sensitive to DPP-4
           enzyme inhibitor drugs; However, for patients with low DPP-4 enzyme activity, DPP-4
           enzyme inhibitor drugs cannot play a stronger role in lowering blood sugar.

        2. SNP of GLP-1 gene. SNP of GLP-1 gene may affect activity or expression level of GLP-1.
           Patients with high GLP-1 level are more sensitive to DPP-4 enzyme inhibitor drugs.

        3. SNP of GLP-1R gene. SNP of GLP-1R gene may affect activity or expression level of
           GLP-1R. Patients with high GLP-1R level are also more susceptible to DPP-4 enzyme
           inhibitor drugs.

      However, studies on the hypoglycemic effect of DPP-4, GLP-1 and their receptors on DPP-4
      enzyme inhibitors in the treatment of T2DM are rare, which is not conducive to the evaluation
      of individualized treatment of such drugs. Therefore, this chapter intends to select SNP
      sites with high mutation frequencies of DPP-4, GLP-1 and GLP-1R genes to study the mutation
      frequencies of these SNPs in diabetic patients and non-diabetic patients and their effects on
      DPP-4 enzyme inhibitor sitagliptin's hypoglycemic effect on T2DM patients.
    

Intervention name(s): Sitagliptin
Intervention type(s): Drug
Intervention description(s): 100mg.QD for 3 months
Other intervention name(s): Januvia
Intervention MeSH terms: Sitagliptin Phosphate
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: DPP-4; GLP1R ; gene polymorphism research; diabetes