Haufinyane tjena, British Journal of Clinical Pharmacology e phatlalalitse tataiso ea pele ea bongaka e ntlafalitsoeng ke Setsi sa Botle sa UK bakeng sa Saense ea Taolo le Ntlafatso ho Pharmacogenomics (CERSI PGx), e nang le sehlooho se reng "Teko ea genotype ea CYP2C19 bakeng sa clopidogrel: Tataiso e ntlafalitsoeng ke Setsi sa Botle sa UK bakeng sa saense ea taolo le boqapi ho pharmacogenomics (CERSI PGx)". Tokomane ena ea bohlokoa e shebana le bohlokoa ba kliniki ba genotyping ea CYP2C19 ho tataisa phekolo ea clopidogrel.
Mabapi le CERSI PGx
CERSI PGx ke e 'ngoe ea litsi tse supileng tsa taolo ea saense le boqapi tse tšehelitsoeng ke' muso oa UK tse qalileng ka Pherekhong 2025. E etelletsoe pele ke Univesithi ea Liverpool, e tšehelitsoe ka kopanelo ke Innovate UK, Lekhotla la Lipatlisiso tsa Bongaka (MRC), Setsi sa Taolo ea Lihlahisoa tsa Meriana le Bophelo bo Botle (MHRA), le Ofisi ea Saense ea Bophelo (OLS). Setsi sena se ikemiselitse ho potlakisa kopanyo e sireletsehileng le e sebetsang ea pharmacogenomics (PGx) ho Tšebeletso ea Naha ea Bophelo (NHS) ka ho sebetsana le litšitiso tsa bohlokoa tsa ts'ebetsong. Tataiso ena e tšoaea tataiso ea pele ea bongaka e fanoeng ho tloha ha CERSI PGx e theoa.
Hobaneng CYP2C19 e le ea Bohlokoa bakeng sa Clopidogrel
CYP2C19 ke setho sa bohlokoa sa lelapa la li-enzyme tsa cytochrome P450, se ikarabellang bakeng sa ho kenya tšebetsong metabolism kapa ho emisa ts'ebetso ea meriana e mengata. Li-polymorphism tsa liphatsa tsa lefutso ho CYP2C19 li lebisa liphapang tse kholo lipakeng tsa batho ka bomong metabolism ea lithethefatsi, e leng se amang katleho le polokeho.
Clopidogrel ke setlhare se sebediswang haholo sa antiplatelet bakeng sa ho thibela diketsahalo tsa thrombotic ho lefu la methapo ya pelo, stroke ya ischemic, lefu la methapo ya peripheral, le fibrillation ya atrial. Jwalo ka setlhare se thusang, clopidogrel e hloka ho kenngwa tshebetsong ha metabolism ke CYP2C19. Tataiso ena e arola batho ka di-metaboliser tse potlakileng haholo, tse tloaelehileng, tse mahareng, le tse fokolang ho latela mofuta wa CYP2C19. Di-allele tse lahlehetsweng ke tshebetso (mohlala, CYP2C192 le *3*) - tse mahareng le tse fokolang - di ke ke tsa kenya tshebetsong clopidogrel ka katleho, e leng se lebisang ho thibeleng ho lekaneng ha platelet le kotsi e eketsehileng ya thrombosis e iphetang.
Khafetsa ea allele ea CYP2C192 ke hoo e ka bang 15% ho Maeurope, 30% ho MaAsia Boroa, 'me e fihla ho 60% ho baahi ba matsoalloa a Leoatle.
Keletso ea Bohlokoa: Teko ea Universal CYP2C19 bakeng sa Clopidogrel
Tataiso e re, ho sa tsotelehe sesupo, bakuli bohle bao clopidogrel e ba nahanelang ba lokela ho feta ho bona.CYP2C19tlhahlobo ea liphatsa tsa lefutso.Ho latela liphetho, phekolo ea antiplatelet e lokela ho ntlafatsoa:
-Li-metaboliser tse fokolangBa lokela ho qoba clopidogrel 'me ba sebelise ka ho khetheha meriana e meng e sa itšetleheng ka metabolism ea CYP2C19, joalo ka ticagrelor kapa prasugrel.
-Li-metaboliser tse maharengHape ba lokela ho nahana ka meriana e meng kapa mekhoa e fetotsoeng ho e-na le ho eketsa tekanyo ea clopidogrel feela.
UK, clopidogrel e amohetsoe bakeng sa thibelo ea bobeli ea liketsahalo tsa atherothrombotic, bakeng sa tlhaselo ea ischemic ea nakoana e itekanetseng ho isa ho e phahameng (TIA) kapa stroke e bobebe ea ischemic, le bakeng sa ho thibela liketsahalo tsa atherothrombotic le thromboembolic ho atrial fibrillation.
Ka Nģ'ane ho Clopidogrel: Meriana e Meng Moo Tlhahlobo ea Genotype ea CYP2C19 e Leng Bohlokoa
Boleng ba genotyping ea CYP2C19 bo fetela hole ho feta clopidogrel. Jwalo ka enzyme e kgolo e fetolang mmele ya sethethefatsi, CYP2C19 e boetse e bapala karolo ya bohlokwa metabolism ya voriconazole, meriana e mmalwa ya ho thibela kgatello ya maikutlo, le di-proton pump inhibitors (PPIs). Ditataiso tse ngata tsa matjhaba le tsa naha di kgothaletsa ho ikgetha ha dithethefatsi tsena ka tataiso ya mofuta wa genotype.
1. Meriana e thibelang ho tepella maikutlo (SSRIs)
Li-inhibitor tse khethiloeng tsa serotonin reuptake (SSRIs) – tse kang sertraline, citalopram, le escitalopram – ke metsoako ea pele ea khatello ea maikutlo ’me haholo-holo li sebelisoa ke CYP2C19. Mosebetsi oa enzyme ea CYP2C19 o khetholla ka ho toba khatello ea mali ea meriana ena maling. Li-metaboliser tse fokolang li na le phokotso ea 30%–60% ea ho tlosoa ha meriana, e leng se etsang hore li be le liphello tse mpe tse kang ho lelefatsa nako ea QT le ho kokobetsa. Li-metaboliser tse potlakileng haholo hangata li na le mahloriso a plasma a ka tlas’a phekolo, e leng se lebisang karabelong e liehang ea kalafo le kotsi e eketsehileng ea ho khaotsa meriana.
Tataiso ea 2023 Clinical Pharmacogenetics Implementation Consortium (CPIC) e bolela hore li-metaboliser tse fokolang tse nkang citalopram kapa escitalopram li na le kotsi e phahameng ea ho lelefatsa nako ea QT 'me li khothaletsa phokotso ea tekanyo ea 50%. Tataiso ea 2021 Dutch Pharmacogenetics Working Group (DPWG) e eletsa hore li-metaboliser tse fokolang li lokela ho fumana tekanyo e phahameng ea escitalopram e fokotsoe ka 50%, le hore li-metaboliser tse potlakileng haholo li lokela ho qoba escitalopram ka ho feletseng. Bakeng sa sertraline, DPWG e khothaletsa tekanyo ea letsatsi le letsatsi e sa feteng 75 mg ho li-metaboliser tse fokolang.
Habohlokoa, Tumellano ea Litsebi tsa Machaena e sa tsoa hatisoa mabapi le Teko ea Pharmacogenomic ho Psychiatry (2025) - e ntlafalitsoeng ke Sehlopha sa Tšebelisano ea Bongaka ba Precision sa Mokhatlo oa Machaena oa Psychiatry - e kenyelletsa ka ho hlaka likhothaletso tsa ho etsa genotyping ea CYP2C19. Polelo ea tumellano e hlokomela hore likhothaletso tsa tokiso ea tekanyo ho tsoa litataisong tsa machaba tse kang CPIC le DPWG bakeng sa lienzyme tse fetolang lithethefatsi (ho kenyeletsoa le CYP2C19) li ka sebelisoa bakeng sa baahi ba Machaena. Ka hona, ho etsa genotyping ea CYP2C19 pele ho qala kalafo ea SSRI (mohlala, escitalopram) ho nolofalletsa ntlafatso ea tekanyo kapa ho fetohela ho meriana e meng e sa fetoloang ke CYP2C19, ka hona ho fihlella kalafo e nepahetseng, ho ntlafatsa sekhahla sa karabelo, le ho fokotsa liketsahalo tse mpe.
2. Lithibela-pompo tsa Proton (PPI)
Lithibela-mafu tsa pompo ea proton – ho kenyeletsoa omeprazole, lansoprazole, le pantoprazole – li sebelisoa haholo bakeng sa mathata a amanang le asiti a kang lefu la reflux ea gastroesophageal le liso tsa peptic. Metabolism ea tsona le eona e itšetlehile haholo ka CYP2C19. Bakuli ba nang le li-genotype tse fapaneng tsa CYP2C19 ba bontša phapang e kholo karabelong ea li-PPI. Bajari ba tahlehelo ea li-allele tsa ts'ebetso (*2, *3) ba na le keketseho e kholo ea ho pepesehela lithethefatsi, e leng se ka eketsang khatello ea asiti empa hape se eketsa kotsi ea litlamorao tse mpe. Ka lehlakoreng le leng, li-metaboliser tse tloaelehileng li na le mahloriso a tlase a plasma 'me li ka ba le khatello e fokolang ea asiti, leha phapang lipakeng tsa batho ka bomong e ntse e le kholo.
Tataiso ea CPIC ea 2020 bakeng sa li-PPI e eletsa hore li-metaboliser tse sebelisang omeprazole kapa lithethefatsi tse tšoanang li fetole moriana kapele haholo, e leng se fellang ka ho se lekane ha mahloriso a mali le ho fokotseha ha asiti ho fokolang. Ho bakuli bana, tekanyo e lokela ho eketsoa 'me karabelo ea kalafo e behoe leihlo. Bakeng sa li-metaboliser tse fokolang, ho tlosoa ha meriana ho lieha 'me mahloriso a mali a mali a ka eketseha; leha katleho e ka ba betere, monyetla oa chefo ea lithethefatsi oa eketseha. Phokotso ea tekanyo le tlhokomelo ea karabelo ke lintho tse utloahalang tse lokelang ho nahanoa. Ka hona, bakeng sa bakuli ba qalang kalafo ea PPI kapa ba nang le karabelo e mpe kapa litlamorao tse mpe, ho khothaletsoa hore CYP2C19 genotyping e tataise tekanyo e ikhethileng, ho ntlafatsa katleho, le ho fokotsa liketsahalo tse mpe.
3. Voriconazole
Voriconazole ke setlhare se seholo sa ho thibela dikokwana-hloko se sebediswang ho phekola ditshwaetso tse tebileng tsa fungus tse kang aspergillosis e hlaselang. E na le monyetla o moqotetsane wa kalafo: mahloriso a phahameng haholo a plasma a eketsa kotsi ya chefo ya sebete le mathata a pono, ha mahloriso a tlase a fella ka ho hloleha ha kalafo. Metabolism ya voriconazole e tsamaiswa haholo ke CYP2C19, mme di-polymorphism tsa lefutso di na le tshusumetso e kgolo mahlorisong a yona a plasma.
CPIC e phatlalalitse tataiso e inehetseng mabapi le CYP2C19 le voriconazole ka 2016. E bolela hore li-metaboliser tse potlakileng haholo li fokolitse mahloriso a voriconazole 'me hangata li hlōleha ho fihlela maemo a phekolo a reriloeng. Li-metaboliser tse fokolang li na le mahloriso a phahameng a trough le kotsi e eketsehileng haholo ea likarabo tse mpe. Tataiso ea CPIC e fana ka likhothaletso tse khethehileng tsa tekanyo ho latela mofuta oa genotype. Mohlala, li-metaboliser tse potlakileng haholo tsa batho ba baholo li lokela ho fumana li-agent tse ling tsa mola oa pele tse sa itšetleheng ka metabolism ea CYP2C19, joalo ka isavuconazole, liposomal amphotericin B, kapa posaconazole. Ka hona, genotyping ea CYP2C19 pele ho phekolo ea voriconazole e nolofalletsa ho nooa ka tekanyo e ikhethileng le ho fokotsa liketsahalo tse mpe tse amanang le lithethefatsi.
Bohlokoa ba Kliniki: Ho Etsa Hore Meriana e Tšepahale Haholoanyane
Tataiso e sa tsoa lokolloa e boetse e beha CYP2C19 genotyping e le ea pele ho meriana e nepahetseng. Leha ho le joalo, ho bohlokoa ho hlokomela hore ts'ebeliso ea bongaka ea CYP2C19 genotyping e fetela hole ho feta clopidogrel - ho tloha ho voriconazole (antifungal) le SSRIs (antidepressants) ho ea ho li-inhibitor tsa pompo ea proton bakeng sa ho fokotsa acid. CYP2C19 genotype e sebetsa e le "sesupa-tsela" bakeng sa kalafo ea meriana.
Ha meriana e nepahetseng e ntse e amoheloa ka bongata, palo e ntseng e eketseha ea litataiso tse nang le matla e kenyelletsa tlhahlobo ea liphatsa tsa lefutso tsa CYP2C19 mesebetsing ea kamehla ea meriana. Bakeng sa bakuli, ho tseba mofuta oa bona oa liphatsa tsa lefutso tsa CYP2C19 ho ba thusa ho utloisisa boemo ba bona ba karabelo ea meriana 'me ho nolofalletsa ho etsa liqeto tse arolelanoang le ngaka ea bona ho nts'etsapele moralo o loketseng haholoanyane oa kalafo. Bakeng sa lingaka, ho kopanya liphetho tsa liteko tsa liphatsa tsa lefutso tse nang le sepheo liqetong tsa ho fana ka meriana ke mokhoa o matla oa ho ntlafatsa boleng ba kalafo le ho netefatsa polokeho ea mokuli.
Teko ea Macro le Micro'sTharollo ea ho Hlahisa Li-Genotype tsa CYP2C19
Teko ea Macro le Micro e fana ka kit ea CYP2C19 genotyping e thehiloeng ho sistimi e ntlafalitsoeng ea phetoho ea amplification refractory (ARMS) e kopantsoeng le li-probe tsa Taqman tse nang le likarolo tse latelang:
-Kakaretso e felletseng ea allele– e lemohaCYP2C192, *3, le *17ntle le ho fetoa ke mefuta ya bohlokwa.
-Taolo e matla ea boleng– e kenyelletsa ditaolo tse mpe/tse ntle, taolo ya kahare, le enzyme ya UDG bakeng sa taolo ya boleng ba maemo a mane ho netefatsa diphetho tse nepahetseng.
-Ho ntšoa ka boiketsetso– e tsamaisana le sesupa-madi sa nucleic acid se iketsang ka botlalo sa Macro & Micro-Test, se ntlafatsang bokgoni ba ho sebetsa.
-Ho lumellana ho pharaletseng– e sebetsa le disebediswa tse tsebahalang tsa PCR tsa nako ya nnete tse fumanehang mmarakeng, ho kenyeletswa le ABI 7500 Hongshi SLAN 96P.
-Tlhaloso ea sephetho e iketsahalletseng– software e inehetseng ea tlhahlobo (ho ABI 7500, SLAN 96P, jj.) e nolofalletsa tlhaloso ea liphetho ka boiketsetso, e ntlafatsang bokhoni.
-Boiketsetso bo itokiselitseng ba POCT– HWTS AIO800 Sehlahlobi sa ho Eketsa Matlafatso sa Nucleic Acid ka Botlalo se nolofalletsa ts'ebetso ea "sampole ho kena le ho tsoa".
Ka tsoelo-pele e tsoelang pele ea pharmacogenomics, ho lebelloa hore genotyping ea CYP2C19 e tsoele bakuli molemo, e fetisetsa meriana e nepahetseng ho tloha khopolong ho ea ho mokhoa o tloaelehileng oa bongaka. Tataiso e sa tsoa hatisoa ea CERSI PGx e tiisa karolo ea bohlokoa ea tlhahlobo ea CYP2C19 eseng feela bakeng sa clopidogrel empa hape le bakeng sa lethathamo le ntseng le hola la meriana, ho kenyeletsoa le meriana e loantšang khatello ea maikutlo, li-inhibitor tsa pompo ea proton, le voriconazole. Ho nolofatsa ho amoheloa ho pharaletseng ha lengolo la ngaka le tataisoang ke genotype, litharollo tsa liteko tse tšepahalang le tse bonolo ho li sebelisa lia hlokahala. Potefolio ea liteko tsa pharmacogenomic ea Macro & Micro-Test, e nang le kakaretso e felletseng ea allele, taolo e matla ea boleng, le liforomo tse itokiselitseng boiketsetso, e ikemiselitse ho tšehetsa bafani ba tlhokomelo ea bophelo ho kenya tšebetsong meriana e nepahetseng le qetellong ho sireletsa bophelo bo botle ba mokuli.
Lihlahisoa tse Amanang:
Litšupiso:
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3. Setsi sa Naha sa Bophelo bo Botle le Tlhokomelo e Hlomphehang (NICE). Teko ea genotype ea CYP2C19 ho tataisa tšebeliso ea clopidogrel kamora stroke ea ischemic kapa tlhaselo ea ischemic ea nakoana. Tataiso ea tlhahlobo ea lefu DG59. E phatlalalitsoe: 31 Phupu 2024.
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Nako ea poso: Mmesa-22-2026