The Correlation Between Primary Failure And Hypoglycemic Reaction After Treatment With Gliclazide In Type 2 Diabetes Mellitus And SUR1 Gene Polymorphism

Objection:To investigated therapeutic effect andhypoglycemic reaction of patient with type 2 diabetes mellitus in Hanpopulation in Tianjin after taking gliclazide, and assessed correlationit with Ser1369Ala gene polymorphism in sulfonylurea receptorl.Methods:A total of 116 patietents with type 2 diabetesmellitus were involved in the study(82 male, 84 female, average age was50.42±7.89 years). They were diagnosised diabetes mellitus less than 5years. They not only took any hypoglycemic medicines no more than aweek in the recent 2 months, but also had not to take any hypoglycemicmedicines in the latest week.Their fasting plasma glucose level wasbetween 7.8～15.0mmol/L and body weigh index was less than28kg/m~2. All patitents were given gliclazide to treat for 8 weeks andobserved the efficacy of medicine and hypoglycemic reaction. GenomicDNA was extracted from anticoagulant whole blood. The sulfonylureareceptorl gene polymorphism was determined by Taqman fluorescentquantitation polymerase chain reaction analysis. According to singlenucleotide polymorphism they were divided into 3 groups tocompare.Results:(1) Distribution in Ser1369Ala gene polymorphismof sulfonylurea receptor 1 possesses colonial representation byHardy-Weinberg equilibrium law analysised. (2) tt genotype(0.241) and t allele(0.67) of sulfonylurea receptor 1 were more higher in patientswith type 2 diabtes mellitus than in normal control population(0.123,0.415),P＜0.05. (3) The frequency distribution of genotypes had nostatistical significance between native population in different areas andJapanese population, but they had significant deviation to compare withthe European white people and the African black people. (4) tt genotypewas related with medical effect of gliclazide and number of times thatappearanceing hypoglycemic reaction were negtive correlation withgenotypes.(5) Fasting insulin level and homeostasis model assessment ofβcell fuction index was lower, Total cholesterol, trigtyceride and Low densitylipoprotein level raised in patients with tt genotypes.Conclusions:(1) SUR1 gene is possibly a susceptible gene fortype 2 diabetes mellitus. (2) Ser1369Ala gene polymorphism ofsulfonylurea receptor1 possesses ethnic specificity. (3) Ser1369Ala genepolymorphism of sulfonylurea receptor1 is relative to primary failure ofsulfonylurea drug and number of times that appearanceinghypoglycemic response, which possibly owing to tt genotypeinfluencing the function of sulfonylurea receptor 1 and reducing the secretionofβcell. (4) Sulfonylurea receptor 1 gene participates lipid metabolism,blood lipid in tt genotypepatients with type 2 diabetes mellitus is elevated.