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The Association Study Of PPARa Gene Polymorphism And Early-onset Type2Diabetes And Its Complications

Posted on:2014-03-12Degree:MasterType:Thesis
Country:ChinaCandidate:Y MaFull Text:PDF
GTID:2254330425970197Subject:Internal Medicine
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Objective: To explore the correlation between the common PPARα gene polymorphismand early-onset type2diabetes and its complications.Methods:893patients of type2diabetic were selected (503for male and390forfemale).The diagnosis standard for early-onset and late-onset is on the basis of age at40years old. In this study, there are421cases for early-onset type2diabetic subjects (276for male and145for female with an average age of36.72±4.89years old) and472casesfor late-onset type2diabetes subjects (227for male and245for female with an averageage57.25±7.84years old). The DNA of peripheral blood leukocytes were extractedfrom all the subjects. PPARαL162V, C2528G and PPARαV227A gene polymorphismwere detected by DNA polymerase chain reaction (PCR) and enzyme reaction and thento analyse and compare the correlation between genotype and clinical biochemicalindicators and complications of diabetes.Results:1.FPG,2hPG and HOMA-IR of early-onset T2DM group are higher than late-onsetT2DM group. Chol, TG and Apo-B of early-onset group were significantly increased,with a high level of UA. At the same time, the incidence of non-alcoholic fatty liver inearly-onset group rose significantly. The high familial aggregation tendency of diabetesis more pronounced.2.The genetype distribution of PPARαL162V, PPARαC2528G, PPARαV227A:Theoverall frequencies of LL,LV,VV in early-onset T2DM group were respectively93.3%,0.0%,6.7%and97.0%,0.0%,3.0%in late-onset T2DM group. The allele frequencies ofL162and V162in early-onset T2DM group are93.3%and6.7%.And in late-onsetT2DM group, they are97.0%and3.0%. The overall frequencies of GG, GC, CC inearly-onset T2DM group were91.7%,5.2%,3.1%, and95.6%,3.4%,1.0%in late-onsetT2DM group respectively. The allele frequencies of G2528and C2528in early-onsetT2DM group are94.3%and5.7%, and in late-onset T2DM group, they are97.3%and 2.7%. The overall frequencies of VV, VA, AA in early-onset T2DM group were93.8%,6.2%,0.0%, and84.5%,15.5%,0.0%in late-onset T2DM group respectively. The allelefrequencies of V227and A227in early-onset T2DM group are93.8%and6.2%, and inlate-onset T2DM group, they are84.5%and15.5%. There was statistical difference inthe gene type frequency distribution between the two groups.3.The levels of FPG,2hPG, Chol, TG and Apo-B in V162isoforms are increased.The level of HOMA-beta is decreased. The level of HOMA-IR is risen; V162has a highlevel of UA. At the same time, the incidence of V162subtypes in non-alcoholic fattyliver was higher than the L162subtypes.4.The levels of FPG, HOMA-IR, Chol, TG and UA in C2528subtypes wereincreased. At the same time, the incidence of C2528subtypes in non-alcoholic fattyliver and macrovascular were significantly risen.5. The levels of FPG、Chol、TG、Apo-B and the incidence of macrovascular in A227subtypes were lower than V227subtypes.Conclusion:1.The early-onset group has severe lipid disorders, elevated uric acid water, badislet function, higher incidence of non-alcoholic fatty liver and significant familialaggregation tendency.2.The variation of PPARαV162V、C2528G in early-onset group is higher than thelate-onset group in Dalian.3.L162V subtypes has glucose and lipid disorders, uric acid disorders, severeinsulin resistance, higher incidence of non-alcoholic fatty liver.4.C2528subtypes has serious metabolic disorders and severe insulin resistance.And the incidence of diabetic macrovascular morbidity and non-alcoholic fatty liver issignificantly higher.5.The levels of TC and Apo-B and the incidence of macro vascular in A227subtypes were lower than V227subtypes.6.The gene polymorphism of PPARαL162V, PPARαC2528G, PPARαV227APPARαL162V, C2528G may be associated with early-onset type2diabetes ofglycolipids and uric acid metabolic disorders. The variation of PPARαL162V andPPARαC2528may be involved in the development non-alcoholic fatty liver. Maybethere is a positive correlation between the variation of PPARαC2528and type2diabetesdisease macrovascular. And perhaps the polymorphism of PPARαV227A is a protected factor for lipid disorders and T2DM macrovascular.
Keywords/Search Tags:early-onset type2diabetes mellitus, peroxiisome roliferator-activated receptor alpha(PPARα), gene polymorphism
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