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Genetic Association Study With Metabolic Diseases And Peripheral Artery Occlusive Disease In Elderly

Posted on:2015-09-08Degree:MasterType:Thesis
Country:ChinaCandidate:J H YangFull Text:PDF
GTID:2284330467460878Subject:Geriatrics
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Part OneGenetic Association Study with Metabolic Syndrome and Metabolic-Related Traitsin Elderly on the Wanshoulu AreaBackground: The metabolic syndrome (MetS) was known as partly heritable, while thenumber of genetic studies on MetS and related diseases among Chinese elderly waslimited.Methods: A2,014cross-sectional analysis was performed among the elderly populationfrom September2009to June2010in Beijing, China. A742ten-year longitudinal studywas carried out among the same elderly population from2001to2010. Biochemicalprofile and anthropometric parameters of all the participants were measured. Theassociations of22polymorphisms located within17candidate SNPs (MTHFR, PPAR,LPL, INSIG, TCF7L2, FTO, KCNJ11, JAZF1, CDKN2A/B, ADIPOQ, WFS1, CDKAL1,IGF2BP2, KCNQ1, MTNR1B, IRS1, ACE) with obesity, diabetes, metabolic phenotypesand MetS were examined in both studies.Results: In this Chinese elderly population, overweight, central obesity, diabetes,dyslipidemia, hypertension, and MetS were present in48.3%,71.0%,32.4%,75.7%,68.3%and54.5%of subjects, respectively. In the cross-sectional analyses, no SNP wasfound to be associated with the MetS. Genotype TT of SNP rs4402960within the geneIGF2BP2(odds ratio=0.479,95%confidence interval:0.316-0.724, p=0.001) wasassociated with overweight and genotype CA of SNP rs1801131within the geneMTHFR (odds ratio=1.560,95%confidence interval:1.194-2.240, p=0.001) wasassociated with hypertension. However, no association was observed in the longitudinalanalyses.Conclusions: SNP rs4402960was associated with overweight and rs1801131wasassociated with hypertension. However, no SNP was identified to be significantlyassociated with MetS in our study. Part TwoGenetic association study between rs7566605located in INSIG2with obesity andlipids in Elderly on the Wanshoulu AreaBackground: The SNP (rs7566605) located within gene INSIG2was reported to beassociated with obesity in previous multiple cohorts. However, few studies haveinvestigated the effect of the loci on lipids metabolism in Chinese.Methods: A2014cross-sectional population sample and a742ten-year longitudinalsample were obtained in a same method and same elderly population from September2009to June2010in Beijing, China. All the participants were measured for biochemicalprofile and anthropometric parameters. The associations between marker rs7566605with obesity and dyslipidemia, including hypercholesterolaemia,hypertriacylglycerolaemia or low HDL-c, were analyzed with a variety of geneticmodels in both samples.Results: In Chinese elderly sample, allele C in loci rs7566605of INSIG2was observedto be positively associated with dyslipidemia, hypertriacylglycerolaemia and low-HDL,while showed a protective effect on hypercholesterolaemia. Dominant andheterogeneous co-dominant model might be main genetic model for the gene. However,no effect was observed on BMI for the variant in our sample, either.Conclusions: The polymorphism rs7566605within the gene INSIG2was related withdyslipidemia and lipid-related phenotypes in Chinese population, while the relationshipbetween the loci and obesity was not identified. The conclusions need to be furtherconfirmed in a larger sample with strict diet controlled and more useful information. Part ThreeGenetic Association Study with Peripheral artery occlusive disease in Elderly onthe Wanshoulu AreaBackground: Peripheral artery occlusive disease (PAOD) is an atheroscleroticsyndrome which will increase the risks of morbidity or mortality of coronary arterydisease. Higher disability or mortality was observed as the population ages. Ignoring thedisease risks, morbidity and mortality associated with PAOD among older PAODpatients will lead to a severe public health burden. Fully understanding the predisposingrisk factors is benefit for the screening and management for PAOD patients.Research Design and Methods: Two population-based cross-sectional studies wereconducted in a2101sample on Wanshoulu Area of Beijing, China. All the participantswere measured for biochemical profile and anthropometric parameters. PAOD wasassessed by an ankle-arm systolic blood pressure index (ABI) of <0.90. The associationsof11polymorphisms located within9candidate SNPs (ICAM-1, MPO, MMP-9, MIF,LIPC, ABCA1, MTR, MTHFR, APOE) with PAOD were examined.Results: The prevalence of PAOD was7.0%(8.1%in male and6.2%in female) in oursample. The prevalence was increased as aging in both female and male samples. In themultiple variable analysis, genotype AA of SNP rs2230806within the gene ABCA1(OR=4.082,95%CI:1.561-10.671, p=0.004) was associated with PAOD in male.However, no SNP was found to be associated with PAOD in female.Conclusion: Genotype AA of SNP rs2230806located within gene ABCA1wasassociated with PAOD in male elders. Sex differences exist in the susceptibility toPAOD.
Keywords/Search Tags:Candidate genes, obesity, diabetes, metabolic syndrome, Chinese elderlyDyslipidemia, INSIG2, Obesity, Chinese elderlyPeripheral artery occlusive disease (PAOD), elderly, sex
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