Relationship Between The SUR1 Gene Polymorphism And Clinical Response Of Gliclazide

Objective The incidence of type 2 diabetes is going up gradually these years. However, there is a non-full-satisfaction therapeutic effect of antidiabetes. A prognosticating system of therapeutic effect of antidiabetes is needed for type 2 diabetes mellitus patients to realize individualized treatment. In the study, the patients with type 2 diabetes whose pathogenesis was less than 5years were enrolled as the objects. Everyday they were treated by gliclazide that is one of the sulfonylurea drugs. We analyzed genotypes of exonl6-3t and exon 33G/T (S1369A) in this study. The purpose of the present study is to investigate the relationship between the polymorphisms of the 2 positions in sulfonylurea receptor 1 (SUR1) and the therapeutic effect of gliclazide. Our results may be helpful to establish a prognosticating system of therapeutic effect of antidiabetic and an individualized treatment system, which is useful for instructing rational administration.Methods (1) Type 2 diabetes patients whose pathogenesis must be less than 5 years were enrolled according to the diagnostic criteria of the world health organization(WHO) in the 1999 and strict eliminant standard. All of the objects wered treated with oral administration gliclazide daily. Fasting plasma glucose and postprandial plasma glucose of all the objects must be determined and they were given drugs for the next two weeks and answered the questionnaire at the first day, 15th day, 29th day , 43th day and 57th day after enrolled. (2) Extracting and purifying the genomic DNA from the blood samples. (3) we applied allelic discrimination of TaqMan PCR analyzing genotypes of exonl6-3t and exon33G/T (S1369A). (4) Analyze the clinical data.Results In all 135 patients, there were 25 with tt genetype, 42 with cc genetyope, 68 with tc genetype, and the frequency of -3t allele of exon 16 was43.70%;there were 45 with TT genetype, 25 with GG genetyope, 65 with TG genetype, and the frequency of G allele of exon 33 (S1369A) was 42.59% . Before treatment, there were significant difference in the AI30/AG30, history of DM, SP among patients with different genotypes (P<0.05),but other clinical data were no significant difference among patients with different genotypes of exon 33 (S1369A) (P>0.05). All clinical data were no significant difference among patients with different genotypes of exon 16-3. After treatment, the best therapeutic effect was in the patients with GG genetyope of exon 33 (SI369A), and the worst therapeutic effect was in the patients with TT genetyope of exon 33 (S1369A). There was no significant difference in the three different genotype of exon 33 (S1369A) (P>0.05). The therapeutic effect among different genotypes of exon 16-3 was no significant difference (P>0.05).Conclusions In type 2 diabetes patients,the patients with 3t allele of exonl6 or G allele of exon33 (SI369A) have a higher frequency.The therapeutic effect of gliclazide is no difference among the three genotypes of exonl6-3, the patients with mutation of exon 33 (S1369A) have well effect to gliclazide. The polymorphism at -3 position of exon 16 in sulfonylurea receptor -1 gene may be no an prognosticating factor of the therapeutic effect of gliclazide, the polymorphism of exon 33 (SI369A) could affect effect of gliclazide, but further research must be done to confirm the conclusion.