血脂异常的危险因素及脂代谢关联基因相关性研究

Thestudyoftheriskfactorsfordyslipidemiaandtherelevancebetweendyslipidemiaandgenesassociatedwithlipidmetabolism(GREKF10-12)(A2010388)ΟShantouUniversityMasterAcademicDegreeDissertationThestudyofriskfactorsfordyslipidemiaandtherelevancebetweendyslipidemiaandgenesassociatedwithlipidmetabolismADissertationSubmittedtoGraduateSchoolofShantouUniversityApplyingfortheMasterDegreeofMedicineMajorinEpidemiologyandHealthStatisticsByYiDeQingUndertheGuidanceandSupervisionofAssociateProf.ZhangQingyingShantouUniversityMedicalCollegeMay2011.Shantou.ChinaI(TC)(TG)(LDL-C)(HDL-C)23040%SNPsSNPsApoE(LPL)(Genome-WideAssociationStudiesGWAS)ApoErs157580SNPsLDL-CLPLrs326SNPsTGSNP-ApoErs157580CTLPLrs326TCIISNPsBeckmanSNPstreamApoErs157580LPLrs326EPiData3.0SPSS13.0(SPSSInc.,Chicago,USA)SAS9.1(SASInstituteInc.,Cary,NorthCarolina,USA)(X±SD)K-Stχ2logisticχ2logisticHaploviewHardy-Weinberg(GMDR)α=0.051.IIIP0.052.Logistic(OR=1.03)(OR=1.27)(OR=1.16)(OR=1.14)(OR=1.18)(OR=1.91)(OR=1.83)(OR=0.78)(OR=1.05)(OR=1.31)(OR=1.70)(OR=2.70)(OR=1.96)(OR=0.78)3.ApoErs157580LPLrs326Hardy-WeinberApoErs157580CT(P=0.918P=0.743)LPLrs326TC(P=0.067)(P=0.012)LPLrs326TCTCCaOR=3.1(P0.05)4.ApoErs157580CTLPLrs326TCApoErs157580TTLPLrs326CTTTaOR=3.7P0.055.ApoErs157580CTLPLrs326TCApoErs157580TT(aOR=2.6P0.001LPLrs326TCT(aOR=7.0P0.0011.2.LPLrs326TCApoErs157580CT3.ApoErs157580TTLPLrs326CT/TT4.LPLrs326CTTTApoErs157580TTIVABSTRACTBackgroundandobjectiveDyslipidemiareferstotheabnormalitiesofserumlipidmetabolism,includinghigherlevelsoftotalcholesterol(TC),triglycerides(TG),andlowdensitylipoproteincholesterol(LDL-C),andlowerlevelofhigh-densitylipoproteincholesterol(HDL-C).Manyresearcheshaveshowedthatdyslipidemiaisanimportantriskfactorofvariousdiseasessuchashypertension,type2diabetes,stroke,atherosclerosisandcoronaryheartdisease.WiththedevelopmentofeconomyinChina,theimprovementofpeople'slivingstandard,andthechangoflivingandeatinghabits,theincidenceofchronicdiseasessuchasdyslipidemiahasincreasedsignificantly.Lipidlevelshavecloselyrelationwithlivingandeatinghabits.Chaoshanlocatedincoastalandthelocalresidentshaveauniquetraditionalcustomculture,livingandeatinghabitsforalongtime.Ourinitialsurveyhasfoundthattherateofdyslipidemiainthispopulationwasmorethan40percent,anddyslipidemiaincludshighcholesterolandhightriglyceridesprimarily.Dyslipidemiahasbecomeoneoftheimportantchronicnon-communicablediseaseswhichhaveharmfulaffectsonthehealthofchaoshanpeople,however,atpresenttheenvironmentalriskfactorsofdyslipidemiainthepopulationhasnotbeensystemreported.Besidestheenvironmentfactors,dyslipidemiawasalsoaffectedbygeneticfactors.ManystudieshaveshowedthatapolipoproteinEandlipoproteinoflipasewereimportantfactorsintheregulationoflipidmetabolism,thegeneticpolymorphismofwhichwasthesignificantgeneticfactorsthateffectofplasmalipoproteins.Genome-WideAssociationStudies(GWAS)hasconfirmedthatApoErs157580andLPLrs326associatedwithhyperlipidemiawerethedangerouselabelSNPsitesinEuropeanpopulation.However,therelationshipbetweentheSNPsitesanddyslipidemiahasnotyetbeenconfirmedinallofthepeopleespeciallyineasternAsia.Inthisstudy,weresearchedtheenviromentalfactorsinchaoshanpopulationbycase-controlmethodtofindtheriskfactorsofdyslipidemia.Meanwhile,wealsodetectedrs157580andrs326genepolymorphismandanalyzedtheassociationbetweenthemanddyslipidemia.Wefurtherexploretherelationsofinteractionofgene-geneandgene-environmenttodyslipidemia.Theaimofourstudywastocarryouttheeffectiveinterveningmeasurestopromotehealthandreducetheriskofcardiovasculardiseas.MaterialsandmethodsFromMay2010toDecember2010,weselectedsubjectsfromPhysicalExaminationCenterofChaoNanminshenghospitalsandthefirstaffiliatedhospitalofmedicalcollegeofShantouVuniversitybyclustersamplingmethod.Allthesubjects,morethan18ages,havebeeninchaoshanformorethan5years.Weusedepidemiologicsurveymethodtocollectdatasincludingbodymeasurement,questionnaireandbiochemicalexamination.Inordertoresearchtherelationofenvironmentalriskfactorstodyslipidemiabycase-controlmethod,weselected1120patientswithdyslipidemia,including923maleand197female,averageages44.111.6years,and1021caseswithnotdyslipidemia,including694maleand327femal,averageages38.71.7years.Inordertofurtherexploretherelationshipbetweendyslipidemiaandgenepolymorphismrelatedwithlipidmetabolism,wepairedtheobjectsaccordingtoageandgenderandselected384pair’scasesandcontrolsrandomly.WedetectedApoErs157580andLPLrs326SNPsitesbyBeckmanSNPstreamtechnologytoanalyzetherelationshipbetweendyslipidemiaandthesetwogenepolymorphisms.WeestablisheddatabaseandloggeddatabyEpiData3.0.Aftercheckedthedata,weuseSAS9.1andSPSS13.0softwaretoanalyzethem.WecheckedthenormalityofmeasuredatabysinglesampleK-Sgoodness-of-fitmethod.Forthedatawhichwasnon-normaldistribution,wetransformedittonormaldistributionbylogarithmicmethod.Forthegroupedcase-controlstudy,weusedt-testtocomparethequantitativevariablesoftwogroupsandANOVAtesttocomparemeasurementvarianceofmorethantwogroups.Weuseratiotodescripetheenumerationdataandχ2testtodostatisticinference.Toresearchtherelation