原发性高血压与apelin-apj通路基因多态性的相关研究

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1、上海交通大学医学院博士学位论文causlnghypertenslon．⋯ApelinandAPJ(angiotensinreceptor-like1)，anewlyidentifiedpathwaythathasaroleofcounter-regulationoftherenin—angiotensinsystem，havebeenimplicatedinbloodpressureregulation．Inaddition，recentstudiesshowedthatAPJ—apelinsigna

2、lingpathwaymaycontributetothepathophysiologyofhumancardiovasculardiseasesuchaschronicheartfailure(CHF)andhypertensionrelatedmetabolicdisorders．AlthoughtherearemanymolecularstudiesofapelinandAPJ，therelationshipbetweentheirgenevariantsandcardiovasculardis

3、easesarepoorlyknownandwhetherapelinserumlevelsCanbeservedasaphenotypeforhypertensivepatientswithmetabolicdisordersneedtobedemonstrated．Toinvestigatethese，athree-partclinicalstudywasCOnaUCteQaSIO重lOW．●．●⋯Partl．StudyofSingleNucleotidePolymorphismDetection

4、withinApelinandAPJGenesInthestudyofpolymorphismdetection，anindependentsampleof56unrelatedindividualswasrandomlyselectedfromthe上海交通大学医学院博士学位论文populationliving。Shanghaimdeenedfor"glenucleotidepopulationivingInandscreenedtorsinzlenucleotidepolymorphisms(SN

5、Ps)．Potentiallyfunctionalrelevantregionsincludingthe2一kbpromoterregionlocatedupstreamfromthefirstexon，allexonsandexon／intronborderregionsweresequenced．ThroughDNAsequencing，8SNPsidentifiedinapelingeneand7SNPsidentifiedinAPjgene．Amongthem。wefound4SNPsthat

6、werenotinSNPdatabase：apelinG6070C。apelinT-1860C。APJG81AandA彤G612A．Paa2．Family—BasedAnalysisofApelinandAPJGenePolymorphismswithHypertensionAccordingtooursequencingresultandSNPdata,13SNPswerechosenforgenotypinganalysis．Inthefamily-basedstudy，wedetected13S

7、NPsin1060recruitedHanChinesefrom248familieswithEHTwithaimtoidentifythosevariantsandhaplotypesassociatedwithEHTanditsrelatedphenotypes．Wefound2apelinSNPs(rs3761581，T一1860C)and3彳彤SNPs(rs7119375，rs10501367andrs9943582)wereassociatedwithhypertension，bodymas

8、sindex(BMI)andonsetageofhypertension．Ofthe上海交通大学医学院博士学位论文commonhaplotypes，haplotype5(A—T)inapelinandhaplotype5(G—G)in彳彤genewerealsoassociatedwithhypertension，BMIandonsetageofhypertension．Part3．StudyontheAssociationbetweenApelinan