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The Association Of The PPAR Alpha Gene Polymorphism With Macroangiopathyin Type 2 Diabetes

Posted on:2011-12-29Degree:MasterType:Thesis
Country:ChinaCandidate:T GuoFull Text:PDF
GTID:2144360305475688Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Background:This evolving view of atherosclerosis as a metabolic complication has directed attention towards peroxisome proliferators-activated receptors (PPARs) as transcriptional regulators involved in lipid metabolism,inflammation and atherosclerosis.The PPARs is a ligand acti-vated transcription factor being part of the nuclear hormone receptor super-family.Generous data demonstrats expression of all three PPAR isotypes-PPARα,-γ, and-δ/β-the vasculature and inflammatory cells. There is the focus on PPARa, which is expressed mainly in higher energy-requiring tissues like skeletal muscle and heart and kidney as well as the liver. Moreover the most subtypes of PPAR is expressed in endothelial cells, which plays a key role in lipid and glucose metabolism, inflammatory response and energy homeostasis.PPARa has been reported to be activated by long-chain poly-unsaturated fatty acids (Linoleic acid, linolenic acid, EPA, DHA) and leukotriene,as well as by drugs such as the lipid-lowering fibrates.Activation of PPARa has been reported to improve levels of triglycerides, HDL, and the overall atherogenic plasma lipid profile, while also potentially modulating inflammation as well as insulin resistance itself.The main reason for premature death has confirmed which diabetic patients comparaed with vascular disease. Diabetic patients with stroke and coronary heart disease is 2 to 4 times higher than non-diabetic patients.Objective:The purpose of this study is to explore the correlation of PPARa polymorphism to macro-vascular disease and risk factors with type 2 diabetes. Methods:Type 2 diabetes are divided into atherosclerosis group (272cases) and non-atherosclerotic group (113cases). According to duration of type 2 diabetes, they are divided into less than 5 years group (121 cases) and 5-10 years group (122cases) as well as more than 15 years group (74cases).Each of this three groups are divided to atherosclerosis group and non-atherosclerotic group. Collected blood samples and extracted peripheral blood white blood cell genomic DNA to detect PPARa C2528G and L162V polymorphism by the application of polymerase chain reaction-restriction fragment length polymorphism (PCR-PFLP), and calculate genetype and allele frequency of each group as well as differences, simultaneously compare with fasting plasma glucose(FBG),fasting plasma insulin,fasting c peptide,postprandial blood glucose,postprandial insulin, postprandial c peptide,glycated hemoglobin, total cholesterol(TC), trigly-ceride (TG),high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein Al, apolipoprotein B,blood urea nitrogen (BUN), creatinine (CR), uric acid (UA), alanine amino-transferase(ALT),aspartate aminotransferase (AST) between the above groups.Results:Fasting plasma glucose and apolipoprotein B of atherosclero-sis group is higher than non-atherosclerotic group (p<0.05); Fasting plasma glucose and apolipoprotein B of atherosclerosis group are higher than non-atherosclerotic group in duration of less than 5 years(p<0.05); Uric acid of atherosclerosis group is higher than non-atherosclerotic group in duration of 5-10 years(p<0.05); Uric acid of atherosclerosis group in duration of less than 5 years is higher than non-atherosclerotic group in duration of more than 15 years(p<0.05); Glycated hemoglobin of ather-osclerosis group in duration of less than 5 years is higher than non-atherosclerotic group in duration of 5-10 years (p<0.05); Fasting plasma glucose and glycated hemoglobin as well as low density lipoprotein cholesterol of atherosclerosis group in duration of less than 5 years are higher than atherosclerosis group in duration of more than 15 years, however the fasting plasma insulin and postprandial insulin as well as apolipoprotein Al lower atherosclerosis group in duration of more than 15 years (p<0.05). PPARa L162V allele frequency has not statistical difference between atherosclerosis group and non-atherosclerotic group by check-up (χ2=0.13,p>0.05); PPARa C2528G allele frequency has statistical difference between atherosclerosis group and non-atherosclerotic group by check-up(χ2=3.88,P<0.05);The PPARaC2528 allele frequency has statistical difference between atherosclerotic group in duration of less than 5 years and atherosclerotic group in duration of more than 15 years by check-up (χ2=4.02,P<0.05).Postprandial blood glucose and glycated hemoglobin of PPARαL162 gene group are higher than PPARαV162 gene group(p<0.05);Apolipoprotein Al of PPARαG2528 gene group is higher than PPARαC2528 gene group, but the apolipoprotein B lower PPARαC2528 gene group(p<0.05); In PPARαC2528 gene,apolipoprotein B and glycated hemoglobin of atherosclerosis group in duration of less than 5 years are higher than atherosclerosis group in duration of more than 15 years,but the fasting plasma insulin and postprandial insulin as well as apolipoprotein Al lower than atherosclerosis group in duration of more than 15 years(p<0.05).Conclusion:The association of PPARa polymorphism with macro-vascular disease in type 2 diabetes is evident. The association of PPARαC2528G gene variation with macro-vascular disease in advance of onset time in type 2 diabetes is also suggested. It is evident that lipid, insulin and glycated hemoglobin as well as uric acid is related to macro-vascular disease in type 2 diabetes.
Keywords/Search Tags:Peroxiisome proliferator-activated receptor alpha(PPARα), C2528Gpolymorphism, L162Vpolymorphism, Type 2 diabetes, Macrovascular disease
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