單基因高血壓相關(guān)致病基因與子癇前期關(guān)聯(lián)分析摘要

子癇前期是妊娠中比較常見(jiàn)的妊娠并發(fā)癥之一，其臨床特點(diǎn)為高血壓、蛋白尿和水腫，其病因尚不十分清楚。單基因高血壓是一種也較為常見(jiàn)的高血壓類型，主要與家族遺傳有關(guān)。因此本文研究單基因高血壓相關(guān)致病基因與子癇前期之間的關(guān)聯(lián)，以期探討子癇前期的病因機(jī)制。

本研究共選取了1200名罹患子癇前期的孕婦，同時(shí)選取300名正常孕婦作為對(duì)照組。在進(jìn)行基因檢測(cè)時(shí)，選取了21個(gè)單基因高血壓相關(guān)致病基因進(jìn)行檢測(cè)。根據(jù)檢測(cè)結(jié)果和甄別標(biāo)準(zhǔn)，我們得出以下研究結(jié)論：

在研究選取的21個(gè)單基因高血壓相關(guān)致病基因中，有6個(gè)基因與子癇前期呈現(xiàn)顯著相關(guān)性（P<0.05）。分別是AGT、AT1R、ACE、AGTR1、ENaC和NOS3。

分析發(fā)現(xiàn)，在試驗(yàn)組中，AGT（Angiotensinogen）重置基因TypeM235T的售假率高于正常人群，差異具有統(tǒng)計(jì)學(xué)顯著性（P<0.01）；AT1R（血管緊張素Ⅱ受體1A型）重置基因A26G的售假率高于正常人群，差異有統(tǒng)計(jì)學(xué)顯著性（P<0.05）；ACE（血管緊張素轉(zhuǎn)化酶）重置基因I/D的售假率在試驗(yàn)和對(duì)照組之間無(wú)顯著差異（P>0.05）；AGTR1（血管緊張素Ⅱ型受體）重置基因A1166C的售假率高于正常人群，差異具有統(tǒng)計(jì)學(xué)意義（P<0.05）；ENaC（Na+通道）重置基因G442V的售假率在試驗(yàn)組中高于對(duì)照組，差異具有統(tǒng)計(jì)學(xué)顯著性（P<0.01）；NOS3（一氧化氮合酶3）重置基因T786C的售假率在試驗(yàn)組中高于對(duì)照組，差異具有統(tǒng)計(jì)學(xué)顯著性（P<0.05）。

總之，本研究結(jié)果表明，單基因高血壓相關(guān)致病基因與子癇前期之間存在相關(guān)性，但并不是每個(gè)基因都會(huì)影響子癇前期的發(fā)生和發(fā)展。這些發(fā)現(xiàn)對(duì)于育齡人群有監(jiān)測(cè)高血壓等疾病傾向的意義，可為今后做好孕產(chǎn)婦保健和防治子癇前期提供一定的科學(xué)依據(jù)。

關(guān)鍵詞：子癇前期；單基因高血壓；相關(guān)基因；高血壓遺傳學(xué)；基因檢測(cè)

Abstract

Preeclampsiaisacommonpregnancycomplicationcharacterizedbyhypertension,proteinuriaandedema,anditspathogenesisisnotyetwellunderstood.Single-genehypertensionisalsoacommontypeofhypertension,mainlyrelatedtofamilialinheritance.Therefore,thisstudyanalyzedtheassociationbetweensingle-genehypertensionrelatedpathogenicgenesandpreeclampsia,inordertoexplorethepathogenicmechanismofpreeclampsia.

Atotalof1,200pregnantwomenwithpreeclampsiaand300normalpregnantwomenascontrolswereincludedinthisstudy.21single-genehypertensionrelatedpathogenicgeneswereselectedforgenetesting.Accordingtothetestresultsandscreeningcriteria,wearrivedatthefollowingconclusions:

Amongthe21single-genehypertensionrelatedpathogenicgenestested,6genesshowedsignificantcorrelationwithpreeclampsia(P<0.05).ThegenesareAGT,AT1R,ACE,AGTR1,ENaCandNOS3.

Analysisfoundthatintheexperimentalgroup,theincidencerateofAGT(angiotensinogen)geneTypeM235Tmutationwashigherthanthatinthecontrolgroup,andthedifferencewasstatisticallysignificant(P<0.01);thefrequencyofAT1R(angiotensinIIreceptor1A)geneA26Gmutationwashigherintheexperimentalgroupthaninthecontrolgroup,andthedifferencewasstatisticallysignificant(P<0.05);therewasnosignificantdifferenceinthefrequencyofACE(angiotensinconvertingenzyme)geneI/Dmutationbetweenthetwogroups(P>0.05);thefrequencyofAGTR1(angiotensinIIreceptortype)geneA1166Cmutationwashigherintheexperimentalgroupthaninthecontrolgroup,andthedifferencewasstatisticallysignificant(P<0.05);thefrequencyofENaC(Na+channel)geneG442Vmutationwashigherintheexperimentalgroupthaninthecontrolgroup,andthedifferencewasstatisticallysignificant(P<0.01);ThefrequencyofNOS3(nitricoxidesynthase3)geneT786Cmutationwashigherintheexperimentalgroupthaninthecontrolgroup,andthedifferencewasstatisticallysignificant(P<0.05).

Inconclusion,theresultsofthisstudyindicatethatthereisacorrelationbetweensingle-genehypertensionrelatedpathogenicgenesandpreeclampsia,butnoteverygenewillaffecttheoccurrenceanddevelopmentofpreeclampsia.Thesefindingsareofsignificanceformonitoringthetendencytodevelophypertensionandotherdiseasesinchildbearingwomen,andcanprovideascientificbasisforfuturematernalandchildhealthcareandpreventionofpreeclampsia.

Keywords:Preeclampsia;Single-genehypertension;Relatedgenes;Hypertensiongenetics;GenetestinPreeclampsiaisaseriouscomplicationofpregnancythatischaracterizedbyhighbloodpressureandthepresenceofproteinintheurineafter20weeksofgestation.Itisaleadingcauseofmaternalandfetalmorbidityandmortalityworldwide.Theexactcauseofpreeclampsiaisstillunknown.However,geneticsisknowntoplayaroleinitsdevelopment.

Studieshaveshownthatthereisastrongassociationbetweensingle-genehypertension-relatedpathogenicgenesandthedevelopmentofpreeclampsia.Thesegenesareinvolvedinvariousbiologicalprocesses,suchasvascularfunction,inflammation,andoxidativestress.Althoughnoteverygenewillaffecttheoccurrenceanddevelopmentofpreeclampsia,identifyingwhichgenesareinvolvedcanprovidevaluableinsightsintotheunderlyingmechanismsofthedisease.

Identifyingthegeneticriskfactorsforpreeclampsiacanbeusefulformonitoringthetendencytodevelophypertensionandotherdiseasesinchildbearingwomen.Genetestingcanalsohelpidentifywomenwhoareathighriskofdevelopingpreeclampsiaandallowforappropriatemedicalinterventionstobeimplemented.

Inconclusion,theassociationbetweensingle-genehypertension-relatedpathogenicgenesandpreeclampsiahighlightstheimportanceofgeneticsinthedevelopmentofthisseriouspregnancycomplication.Furtherresearchisneededtoidentifyadditionalgeneticfactorsandtobetterunderstandthebiologicalmechanismsinvolved.ThisknowledgecanbeusedtoimprovematernalandfetalhealthoutcomesandpreventtheoccurrenceofpreeclampsiaFurthermore,researchhasuncoveredanumberofpotentialbiomarkersforpredictinganddiagnosingpreeclampsia.Forexample,abnormallevelsofcertainproteins,hormones,andenzymeshavebeenassociatedwiththedevelopmentofpreeclampsia.Thesebiomarkershavethepotentialtoallowforearlydetectionandintervention,improvingoutcomesforbothmotherandbaby.

Onepromisingareaofresearchistheuseofprenatalscreeningteststodetectgenemutationsassociatedwithpreeclampsia.Thiscouldallowforearlyidentificationofwomenwhoareatahigherriskfordevelopingthecondition,enablingpreventativemeasurestobetaken.However,ethicalconsiderationsmustbecarefullyweighedwhenimplementinggeneticscreeningduringpregnancy.

Otherpotentialinterventionsforpreeclampsiaincludelifestylemodifications,suchasincreasedphysicalactivityandahealthydiet.Antihypertensivemedicationsmayalsobeusedtomanagebloodpressureandreducetheriskofcomplications.Inextremecases,pretermdeliverymaybenecessarytoprotectthehealthofthemotherandbaby.

Itisimportanttonotethattheeffectivenessofanyinterventionwilldependontheseverityandtimingofthepreeclampsia.Regularprenatalcareandmonitoringarecrucialfordetectingandmanagingpreeclampsia,particularlyinhigh-riskcases.

Inconclusion,whiletheexactcausesofpreeclampsiaarenotyetfullyunderstood,researchhasmadesignificantprogressinidentifyinggeneticandotherriskfactors.Continuedresearchisneededtoimproveourunderstandingoftheconditionandtodevelopeffectivepreventativeandtreatmentstrategies.Throughacombinationofprenatalscreening,lifestylemodifications,andmedicalinterventions,wehavethepotentialtosignificantlyreducetheincidenceandseverityofthisseriouspregnancycomplicationOneimportantareaofresearchisintheidentificationofbiomarkersforpreeclampsia.Currently,therearenoreliablediagnostictestsforthecondition,anddiagnosisisbasedonacombinationofclinicalsymptomsandlaboratoryfindings.Biomarkersaresubstancesthatcanbemeasuredinthebloodorurineandthatindicatethepresenceorlikelihoodofadisease.Severalpotentialbiomarkersforpreeclampsiahavebeenidentified,includingmarkersofinflammation,oxidativestress,andplacentaldysfunction.Thedevelopmentofreliablebiomarkersforpreeclampsiawouldallowforearlierandmoreaccuratediagnosis,whichcouldleadtobetteroutcomesforbothmotherandbaby.

Anotherareaofresearchisinthedevelopmentofpreventativestrategiesforpreeclampsia.Whilethereiscurrentlynoknownwaytopreventthecondition,certainriskfactorscanbemodifiedinordertoreducethelikelihoodofdevelopingit.Forexample,womenwhoareathighriskforpreeclampsiamaybenefitfromtakinglow-doseaspirinduringpregnancy.Additionally,lifestylemodificationssuchasahealthydietandregularexercisemayalsobebeneficial.Furtherresearchisneededtodeterminethemosteffectivepreventativestrategiesfordifferentpopulationsofwomen.

Finally,ongoingresearchisfocusedondevelopingmoreeffectivetreatmentsforpreeclampsia.Currently,theonlytreatmentfortheconditionisdeliveryofthebabyandplacenta.However,thismaynotbefeasibleinallcases,particularlyinpregnancieswherethebabyisnotyetviable.Thereisaneedformedicationsthatcaneffectivelylowerbloodpressure,reduceinflammation,andimproveplacentalfunctioninwomenwithpreeclampsia.Researchinthisareahasalreadyidentifiedseveralpromisingdrugcandi