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The Association Of Protein Tyrosine Phosphatase 1B Gene Polymorphism In Chinese Patients With Obesity

Posted on:2005-02-28Degree:MasterType:Thesis
Country:ChinaCandidate:T TaoFull Text:PDF
GTID:2144360125468359Subject:Endocrinology
Abstract/Summary:PDF Full Text Request
Obesity is a chronic disease which is very seriously harmful to public health. It is obviously associated with enviroment and heredity. It is the principal risk factor to cardiac disease ,diabetes mellitus,atherosclerotic vascular disease,lipoprotein metabolism disorder and etal. Currently the genetic background that caused obesity is unclear. Protein tyrosine phosphatase 1B (PTP1B) is an important medium during insulin signal convection process. It is a principal regulation agent for insulin sensibitity and body fat composition. Protein tyrosine phosphatase 1B gene is one of insulin resistence predisposing genes. The investigation of the relationship of PTP1B gene polymorphism with insulin resistence may provide some evidence for clarification pathogenesis of obesity. Abroad investigation proved that the PTP1B gene polymorphism is associated with type 2 diabetes mellitus. But the correlation with obesity was still unreported. In this study, Pro387Leu mutation of PTP1B gene was detetected by PCR/Bsl I digestion and 1484insG mutation of PTP1B gene was determined by PCR/SacII I digestion in a group of 305 subjects. The sequence of the mutated gene were determined with Applied Biosystem(A B I)PRISMTM377 DNA sequencer. This experiment establishes a substantial base for further study of etiological factor for obesity.Investigative Method:1. Vein blood which Obesity patient and health control of human genomic DNA were drawn.2. Objective fragment was amplified by polymerase chain reaction. It was digested by Bsl I enzyme after purification. Enzyme cutting products was evaluated by running through 3% agarose gel electrophoresis. Pro387Leu mutationof PTP1B gene were determined by 0.1%bromium/ infrared.3. Objective fragment was amplified by polymerase chain reaction. It was digested by SacII enzyme after purification. Enzyme cutting products was evaluated by running through 12% undenaturing polyacrylamide gel electrophoresis,3'UTR1484insG mutation of PTP1B gene were determined by 0.1%bromium/ infrared.4. The sequence of the mutated gene were detected with Applied Biosystem(A B I)PRISMTM377 DNA sequencer. 5. Clinical markers of patient and control such as fast blood glucose,fast blood insulin ,TG,TC,HDL, LDL,ApoB,body mass index ,waist circumference,hip circumference,body fat composition were observed.Investigative Result:We had detected five examples of a pro387leu mutation of PTP1B gene in simple obesity group and two examples in obesity with type 2 diabetes group, while not in control group. The allele frequency of in simple obesity group is 0.025. The allele frequency of in obesity with type2 diabetes group is 0.01. Although this mutation is association with simple obesity, the more bigger BMI is not associated with the more higher mutation rate variation. In obesity groups is associated with BMI of 27-30kg/m2 .3. All of mutuation were detected in heterozygote our study population. In general obesity group,there were no difference in age,BMI,TC and HDL between Pro/Pro wild type with Pro/Leu heterozygote type . There were difference in waist circumference/hip circumference rate,body fat composition ,fast blood glucose ,fast blood insulin and ApoB between Pro/Pro wild type with Pro/Leu heterozygote type . We had found ten examples of a 1484insG mutation of PTP1B gene in simple obesity group and sixteen examples in obesity with type 2 diabetes group, while eight examples in control group. The allele frequency of in simple obesity group is 10 percent. The allele frequency of in obesity with type2 diabetes group is 16 percent. The allele frequency of in control group is 7.6 percent.As for the allele frequency, there were significant difference in obesity with type2 diabetes group compared with control group and simple obesity group (P<0.05), but no difference in simple obesity group and general obesity group compared with control group(P>0.05). Conclusion:This study demonstrates that the Pro387Leu mutation of PTP1B gene is associated...
Keywords/Search Tags:Obesity, Gene, Polymorphism, Protein tyrosine phosphatase 1B
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