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Associations Of APOA5 Level And APOA5 Gene-1131T/C Single Nucleotide Polymorphism With Metabolic Syndrome Among Elderly Patients

Posted on:2012-04-20Degree:MasterType:Thesis
Country:ChinaCandidate:W J MaFull Text:PDF
GTID:2214330338964278Subject:Geriatrics
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BACK GROUNDThe metabolic syndrome is a public health problem which is characterized by a group of metabolic risk factors in one person. They include abdominal obesity, high triglycerides, low HDL cholesterol, high LDL cholesterol, Insulin resistance or Glucose intolerance and Elevated blood pressure. Each of the components is the risk factor of cardiovascular diseases. Especially, the disturbances of lipid metabolism which is characterized by elevated triglyceride and reduced levels of high-density lipoprotein (HDL) cholesterol is correlated closely with cardiovascular diseases and atheroscleresis. Epidemiological data showed that the morbidity and mortality of cardiovascular disease in MS are both higher than that in the normal people. The mechanism of MS is still unclear recently, it was generally acknowledged that the first and foremost factor of MS is obesity, and then IR which was the core link of occurrence of MS is induced by it. The studies of Helsinki Heart Study and RPOCMA showed that the increase of TG was closely related to IR. So studying of the relationship of MS and cardiovascular diseases at the aspect of regulating TG is of strategic meanings to make effective prevention and treatment, and to decrease the morbidity and mortality of cardiovascular disease in MS.And ApoA5 is a new member of human apolipoprotein family and considered to be a major discovery of Triglyceides, which is identificated by proteomics technique in 2001. Studies with animals and human shown that ApoA5 can regulate the plasma TG level. Mice expressing a human ApoA5 transgene showed a decrease in plasma TG concentrations to one-third of those in control mice, conversely,knockout mice lacking ApoA5 had four times as much plasma TG as control. It has been identified that APOA5 have 16 single nucleotide polymorphism (SNP) sites, and -1131 T/C and 56C/G sits showed most close relationship to the metabolic of TG. The Regulating Effect of ApoA5 level and it's gene single nucleotide polymorphism on TG can provide a new method for the prevention and treatment of MS.OBJECTIVEThe body mass index (BMI), Blood Pressure, Blood-lipid and Blood-glucose were measured and we analyzed the relationships between ApoA5 and these indexes among elder people of metabolic syndrome. The single nucleotide polymorphisms at positions-1131 T/C in ApoA5 gene were determined by polymerase chain reaction restriction fragment length polymorphisms (PCR-RFLP) assay in aged patients with metabolic syndrome. The aim of the thesis is to discuss whether ApoA5 can be a serum marker in elder metabolic syndrome and to provide a new method for the prevention and treatment of Atherosclerosis.METHODSA total of 132 elder persons were recruited from the Shandong university qilu hospital, divided into two groups, one is the group of metabolic syndrome and the other is health control group. The ApoA5 concentrations of all the enrolled patients were determined by ApoA5-ELISA kit, meanwhile the Blood-lipid, Blood-glucose, ApoAl, ApoB100 were determined by Automatic Chemical Analyzer. Then the relationship between ApoA5 and body mass index (BMI), Blood Pressure, Blood-lipid,, Blood-glucose were analyzed. The single nucleotide polymorphisms at positions-1131 T/C in ApoA5 gene were determined by polymerase chain reaction restriction fragment length polymorphisms (PCR-RFLP).RESULTSCompared to the health control group, the level of ApoA5, ApoAl and HDL in metabolic syndrome were obviously lower (P<0.05); as well as TC, TG, LDL-C, FPG, SBP and BMI were obviously higher (P<0.01 or P<0.05). Correlative analysis showed that the level of ApoA5 was in significant negative correlation to TG, TC and BMI(r=-0.987/-0.316/-0.445,P<0.01), meanwhile, it took positive correlation to HDL-C (r=0.278, P<0.01)), but insignificantly correlated with age, LDL-C, ApoAl, ApoB100 and Blood Glucose.ApoA5 allelic frequencies of T,C were 0.435,0.565 and 0.374,0.626 in MS group and control group.There is significant difference in allele and genotype frequencies between the two groups, and C geno type appeared more frequently in patients with MS than normal population in aged people (P<0.05).The frequency of the ApoA5-1131C allele in MS patients was significantly higher than that of the control group (P<0.01). And the level of TG is significantly higher than the others who without it, but TC, LDL-C in patients with the APOA5-1131 C allele are not significantly higher than the others who without it (P>0.05). The serum levels of TG in T/C and C/C genotypes were significantly higher than those in TT type, and the highest is C/C type.CONCLUSIONThere is particularly low level of ApoA5 in patients with metabolic syndrome, and the concentration of it is closely related to TG, TC, HDL-C and BMI. Low level of ApoA5 can be a marker of metabolic syndrome in the aged people.There was a correlation between the ApoA5-1131T> C polymorphism and MS (P< 0.05).And the ApoA5-1131C allele was closely related to the increased serum TG (P < 0.01). The ApoA5-1131C allele might contribute to an increased risk of MS in aged patients.
Keywords/Search Tags:ApolipoproteinsA5(ApoA5), single nucleotide polymorphisms (SNP), metabolic syndrome(MS), Triglyceride(TG), Elderly
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