Study On The Mutation In GLUT4 Gene In Type 2 Diabetes

Insulin resistance is the significant pathogenesis of type2 diabetes. The role of post-receptor defect of insulin is especially predominant in the factors of insulin resistance. Impaired glucose uptake and utilization in peripheral tissues , particularly skeletal muscle and adipocytes, is the major cause of post-receptor insulin resistance. Because the trans-membrane transport of glucose is the rate-limiting step for peripheral tissues utilizing glucose , and this procedure is accomplished by GLUT4, so GLUT4 is considered as an important candidate gene for insulin resistance. On theory , the mutation in GLUT4 gene will result in the variation of GLUT4 molecular configuration and affect bodies' utilization of glucose .The relation of mutation in GLUT4 gene and type 2 diabetes is not distinct so far. The aim of our experiment is to investigate the prevalence of mutation in GLUT4 gene on type 2 diabetes. Using PCR-SSCP analysis, we screened the exon 4a of GLUT4 in 220 type 2 diabetic subjects and 150 normal controls, so as to investigate the role of mutation in GLUT4 gene on type 2 diabetes. Methods: we select the blood samples according to WHO criteria oftype 2 diabetes, extract and purify the genetic DNA from the blood samples of 220 type 2 diabetic patients and 150 normal controls. Using PCR-SSCP analysis, we screened the exon 4a of GLUT4 in diabetic patients and control subjects, then sequence the mutation gene screened by SSCRResults: Four silent mutations (AAC桝AT) at Asn130are detected in 220 diabetic subjects, one is homozygous, the others are heterozygous. The frequency of mutation is 1.82%. We didn't detect any mutation of other types in this group. And no mutation was found in normal controls. There is no difference in the frequency of gene mutation between two groups( *2=1.32, P>0.05). Conclusion: The frequency of gene .mutation in GLUT4 is low in type 2 diabetic subjects in Tianjin, implying that it may not be the primary cause in the pathogenesis of type 2 diabetes. However, since we didn't screen other exons of GLUT4, so we can't confirm whether genetic variation in GLUT4 has association with the pathogenesis of type 2 diabetes in this district. To illustrate this question need further study. Because type 2 diabetes is a multigenic genetic heterogeneoustype 2 diabetes, extract and purify the genetic DNA from the blood samples of 220 type 2 diabetic patients and 150 normal controls. Using PCR-SSCP analysis, we screened the exon 4a of GLUT4 in diabetic patients and control subjects, then sequence the mutation gene screened by SSCRResults: Four silent mutations (AAC桝AT) at Asn130are detected in 220 diabetic subjects, one is homozygous, the others are heterozygous. The frequency of mutation is 1.82%. We didn't detect any mutation of other types in this group. And no mutation was found in normal controls. There is no difference in the frequency of gene mutation between two groups( *2=1.32, P>0.05). Conclusion: The frequency of gene .mutation in GLUT4 is low in type 2 diabetic subjects in Tianjin, implying that it may not be the primary cause in the pathogenesis of type 2 diabetes. However, since we didn't screen other exons of GLUT4, so we can't confirm whether genetic variation in GLUT4 has association with the pathogenesis of type 2 diabetes in this district. To illustrate this question need further study. Because type 2 diabetes is a multigenic genetic heterogeneousdisease, and environmental factors also play consequential role, consequently, single mutation can interact with other mutations in many of the genetic components of insulin signaling network and environmental risk factors so as to increase the susceptivity to type 2 diabetes.