Association Of Human Ghrelin Gene Polymorphism And Cytokine Level With Gestational Impaired Glucose Tolerance

Gestational impaired glucose tolerance (GIGT) as an early change in blood glucose homeostasis, is the intermediate state between normal pregnancy and gestational diabetes. It could be converted into gestational diabetes. GIGT has a similar clinical presentation with gestational diabetes, such as gestational hypertension, hydramnios, macrosomia. Moreover, GIGT cause disturbance of glucose metabolism and lipid metabolism.It has been reported that the protein expression of Ghrelin gene located in Chromosome 3 affects glucose metabolism in balance. In accordance with the principle of informed consent, we choice 196 Han pregnant women who came from the First Affiliated Hospital of Kunming Medical College from November 2008 to November 2009 for the study(including two groups:94 patients with gestational impaired glucose tolerance and 102 normal glucose tolerance women). We assessed common genetic variation of the Ghrelin (ten single nucleotide polymorphisms) in the two groups by the restriction fragment length polymorphism method. In addition, haplotype assays were conducted. The genotype distributions of these ten common polymorphisms in gestational impaired glucose tolerance patients were no significant difference from those of normal controls (P>0.05), and the haplotypes (SNP-1500G—SNP-1062G—SNP-994C—SNP-604G; SNP+408C—SNP+2488G—SNP+3056C; SNP+408A—SNP+2488G—SNP+3056C) of the Ghrelin gene was found to be significantly associated with it (P<0.05). SNP+408C—SNP+2488G—SNP+3056C showed a protective role in gestational impaired glucose tolerance, and SNP-1500G—SNP-1062G—SNP-994C—SNP-604G,SNP+408A—SNP+2488G—SNP+3056C showed susceptible. The haplotypes of the Ghrelin gene was associated with gestational impaired glucose tolerance, and the SNPs was not. The reason of the above condition is that we estimate different haplotypes has different expression activity, and plasma Ghrelin concentration has significantly associated with diabetes. Changes in a single SNP can not have a significant impact.on multi-gene disease such as impaired glucose tolerance.At the same time we randomly select 40 samples in each of the impaired glucose tolerance group and the control group, using Luminex multiplex analysis for the detection of cytokines Level. The results showed that the serum Leptin level has significant difference between GIGT group and control group (P<0.05), and interleukin 6 (IL-6), tumor necrosis factor a (TNF-a), monocyte chemoattractant protein 1 (MCP-1) have no obvious difference between the two groups (P>0.05). It makes Leptin as a potential marker for gestational impaired glucose tolerance. The high level of expression of Leptin cause insulin resistance, while the latter is one of the major reason for abnormal glucose tolerance.The main purpose of the thesis is to find genes and their protein expression which is associated with GIGT, our results provide a basis for the GIGT further study of pathogenesis, and also provide a new target for prevention and treatment of gestational impaired glucose tolerance.