Munguva pfupi yapfuura, British Journal of Clinical Pharmacology yakaburitsa gwara rekutanga rekiriniki rakagadzirwa neUK Centre of Excellence for Regulatory Science and Innovation in Pharmacogenomics (CERSI PGx), rine musoro unoti “CYP2C19 genotype testing for clopidogrel: Gwara rakagadzirwa neUK Centre of Excellence for regulatory science and innovation in pharmacogenomics (CERSI PGx)”. Gwaro iri rinokosha rinotarisa kukosha kweCYP2C19 genotyping mukutungamira clopidogrel therapy.
NezveCERSI PGx
CERSI PGx ndeimwe yenzvimbo nomwe dzesainzi nekuvandudza dzinotsigirwa nehurumende yeUK dzakatangwa muna Ndira 2025. Ichitungamirwa neYunivhesiti yeLiverpool, inotsigirwa nemari pamwe chete neInnovate UK, Medical Research Council (MRC), Medicines and Healthcare products Regulatory Agency (MHRA), uye Office for Life Sciences (OLS). Nzvimbo iyi ine chinangwa chekukurumidzisa kubatanidzwa kwakachengeteka uye kunobudirira kwepharmacogenomics (PGx) muNational Health Service (NHS) nekugadzirisa zvipingamupinyi zvikuru zvekushandisa. Gwaro iri rinoratidza gwara rekutanga rekiriniki rakapihwa kubva pakatangwa CERSI PGx.
Nei CYP2C19 Ichifanira Kukosha paClopidogrel
CYP2C19 inhengo huru yemhuri yecytochrome P450 enzymes, ine basa rekuita kuti mishonga yakawanda ishande kana kuti ishande. Kuwanda kwemajini muCYP2C19 kunotungamira mukusiyana kukuru pakati pemishonga, zvichikanganisa kushanda kwayo uye kuchengetedzeka kwayo.
Clopidogrel mushonga unoshandiswa zvakanyanya kudzivirira matambudziko eropa muchirwere chemwoyo, sitiroko yemwoyo, chirwere cheropa, uye atrial fibrillation. Semushonga unoshanda, clopidogrel inoda kuti metabolic activation ishandiswe neCYP2C19. Gwaro iri rinoisa vanhu muzvikamu zviviri: metabolisers dzinokurumidza, dzinokurumidza, dzakajairika, dzepakati, uye dzisina kunaka zvichibva paCYP2C19 genotype. Zvinotakura kurasikirwa kwemabasa (semuenzaniso, CYP2C192 uye *3*) - metabolisers dzinokurumidza uye dzisina kunaka - hazvigone kushanda zvakanaka neclopidogrel, zvichikonzera kusakwana kweplatelet inhibition uye kuwedzera kwenjodzi yekudzoka kwe thrombosis.
Kuwanda kweCYP2C192 allele kunosvika 15% muvanhu vekuEurope, 30% muvanhu vekuSouth Asia, uye kusvika 60% muvanhu vemuOcean.
Zvinokurudzirwa Zvikuru: Kuongororwa kweClopidogrel kweCYP2C19 kweUniversal
Gwaro iri rinoti, pasinei nechiratidzo, varwere vese vari kutarisirwa kupiwa clopidogrel vanofanira kupihwaCYP2C19kuongorora majini.Zvichibva pamhedzisiro, kurapa kwe antiplatelet kunofanirwa kuve kwakanyatsogadzirwa:
-Mishonga isina kunaka ye metabolismVanofanira kudzivisa clopidogrel uye vanofanira kushandisa mimwe mishonga isingatsamiri pakuchinja kweCYP2C19, yakadai seticagrelor kana prasugrel.
-Zvinoshandiswa pakuchinja kwesimba remuviri (metabolism) pakati nepakativanofanirawo kufunga nezvemamwe mishonga kana mishonga yakagadziriswa pane kungowedzera clopidogrel.
MuUK, clopidogrel inotenderwa kudzivirira zviitiko zve atherothrombotic, kune njodzi yepakati kusvika kune yakanyanya njodzi yekukurumidza kurwiswa kwe ischemic (TIA) kana stroke ye ischemic mild, uye kudzivirira zviitiko zve atherothrombotic uye thromboembolic mu atrial fibrillation.
Kunze kweClopidogrel: Mimwe Mishonga Iyo CYP2C19 Genotyping Yakakosha
Kukosha kweCYP2C19 genotyping kunopfuura clopidogrel. Semushonga mukuru unogadzirisa enzyme, CYP2C19 ine basa rakakosha mukushandiswa kwevoriconazole, mishonga yakawanda inorwisa kushushikana, uye proton pump inhibitors (PPIs). Mitemo yakawanda yepasi rose neyenyika inokurudzira kushandiswa kwemishonga iyi nenzira ye genotype.
1. Mishonga yekuderedza kushushikana (SSRIs)
Mishonga inoderedza serotonin reuptake inhibitors (SSRIs) – yakaita sesertraline, citalopram, uye escitalopram – ndiyo mishonga yekutanga inoderedza kuora mwoyo uye inonyanya kushandiswa neCYP2C19. Mabasa eCYP2C19 enzyme anotarisa zvakananga huwandu hwemishonga iyi muropa. Mishonga isingashandise mishonga zvakanaka ine kudzikira kwe30%–60% mukubviswa kwemishonga, izvo zvinoita kuti iite migumisiro yakaipa senge QT interval lengation uye sedation. Mishonga inokurumidza kushandiswa nekukurumidza inowanzova nehuwandu hweplasma husingarapike, zvichikonzera kunonoka kupindura kwekurapwa uye njodzi yakawedzerwa yekurega kushandisa mishonga.
Gwaro reClinical Pharmacogenetics Implementation Consortium (CPIC) ra2023 rinoti vanhu vanoshandisa citalopram kana escitalopram zvisina kunaka vane njodzi yakakura yekuwedzera nguva yeQT uye rinokurudzira kuderedzwa kwemushonga ne50%. Gwaro reDutch Pharmacogenetics Working Group (DPWG) ra2021 rinoti vanhu vanoshandisa metabolic zvisina kunaka vanofanira kuderedzwa ne50% yemushonga, uye vanhu vanoshandisa ultrapid metaboliser vanofanira kudzivirira escitalopram zvachose. Kune sertraline, DPWG inokurudzira kuti munhu apiwe mushonga wezuva nezuva usingapfuure 75 mg kune vanhu vanoshandisa metabolic zvisina kunaka.
Zvakakosha, gwaro reChinese Expert Consensus on Pharmacogenomic Testing in Psychiatry (2025) rakaburitswa munguva pfupi yapfuura - rakagadzirwa nePrecision Medicine Collaboration Group yeChinese Society of Psychiatry - rinosanganisira zvakajeka mazano eCYP2C19 genotyping. Chirevo cheConsensus chinotaura kuti mazano ekugadzirisa dose kubva kumitemo yepasi rose yakadai seCPIC neDPWG yemishonga inogadzirisa maenzymes (kusanganisira CYP2C19) anogona kutaurwa kuvanhu vekuChina. Nokudaro, CYP2C19 genotyping usati watanga SSRI therapy (semuenzaniso, escitalopram) inobvumira kugadzirisa dose kana kuchinja kune mimwe mishonga isina kugadzirwa neCYP2C19, nokudaro kuwana kurapwa kwakarurama, kuvandudza mhinduro, uye kuderedza zviitiko zvakaipa.
2. MaProton Pump Inhibitors (PPIs)
Mishonga inodzivirira mapombi eproton - inosanganisira omeprazole, lansoprazole, uye pantoprazole - inoshandiswa zvakanyanya pazvirwere zvine chekuita neacid zvakaita segastroesophageal reflux disease uye maronda emudumbu. Kugayiwa kwavo kunoenderanawo neCYP2C19. Varwere vane genotypes dzakasiyana dzeCYP2C19 vanoratidza kusiyana kukuru mukupindura kuPPIs. Vatakuri vekurasika kwemabasa emuviri (*2, *3) vakawedzera zvakanyanya kushandiswa kwemishonga, izvo zvinogona kuwedzera kudzvinyirirwa kweacid asi zvakare kuwedzera njodzi yemigumisiro yakaipa. Kusiyana neizvi, metabolisers dzakajairika dzine huwandu hwakaderera muplasma uye dzinogona kusangana nekudzvinyirirwa kweacid kushoma, kunyangwe kusiyana pakati pemunhu kuchiri kukuru.
Gwaro reCPIC ra2020 rePPIs rinokurudzira kuti vanhu vanoshandisa omeprazole kana mimwe mishonga yakafanana nekukurumidza vagadzirise mushonga uyu, zvichikonzera kusakwana kwehuwandu hwemuropa uye kuderera kweasidhi mumuviri. Muvarwere ava, mushonga unofanirwa kuwedzerwa uye mhinduro yekurapa inotarisirwa. Kune vanhu vanoshandisa mushonga uyu zvishoma nezvishoma, kubviswa kwemushonga uyu kunononoka uye huwandu hwemuropa hunogona kukwira; nepo kushanda zvakanaka kungave kuri nani, mukana wekuti mushonga uyu uve muchetura unowedzerwa. Kuderedzwa kwemushonga uye kutarisa mhinduro yacho zvinhu zvine musoro. Saka, kune varwere vanotanga kurapwa nePPI kana avo vanowana mhinduro isina kunaka kana migumisiro yakaipa, CYP2C19 genotyping inokurudzirwa kutungamira dosing yemunhu mumwe nemumwe, kuwedzera kushanda zvakanaka, uye kuderedza zviitiko zvakaipa.
3. Voriconazole
Voriconazole mushonga wekuuraya fungus wakasiyana-siyana unoshandiswa kurapa hutachiona hwakakomba hwefungus hwakadai seaspergillosis inopararira. Ine mukana mudiki wekurapa: kuwanda kwakanyanya muropa kunowedzera njodzi yekukuvadzwa nehepatocytes uye matambudziko ekuona, nepo kuwanda kushoma kuchikonzera kutadza kurapwa. Kugayiwa kwevoriconazole kunonyanya kukonzerwa neCYP2C19, uye magene polymorphisms ane simba guru pakuwanda kwayo muropa.
CPIC yakaburitsa gwara rakapihwa pamusoro peCYP2C19 nevoriconazole muna 2016. Inotaura kuti mishonga inouraya zvipembenene nekukurumidza yakaderedza huwandu hwevoriconazole mumitsetse uye kazhinji inokundikana kusvika padanho rekurapa rakatarwa. Mishonga isina kunaka ine huwandu hwakakwira mumitsetse uye njodzi yakawedzera yemigumisiro yakaipa. Gwaro reCPIC rinopa mazano chaiwo ekushandisa mishonga zvichibva pamhando ye genotype. Semuenzaniso, mishonga inouraya zvipembenene nekukurumidza mumitsetse yevanhu vakuru inofanira kugamuchira mimwe mishonga yekutanga isingatsamiri pa CYP2C19 metabolism, senge isavuconazole, liposomal amphotericin B, kana posaconazole. Nokudaro, CYP2C19 genotyping isati yatanga kurapwa nevoriconazole inobvumira kupihwa mishonga yega uye inoderedza kuwanda kwezviitiko zvakashata zvine chekuita nemishonga.
Kukosha Kwekiriniki: Kuita Kuti Mishonga Ive Yakavimbika Zvikuru
Gwaro idzva rakaburitswa rinoisa zvakare CYP2C19 genotyping pamberi pemishonga chaiyo. Zvisinei, zvakakosha kuziva kuti kushandiswa kweCYP2C19 genotyping kunopfuura clopidogrel - kubva kuvoriconazole (antifungal) uye SSRIs (antidepressants) kusvika kuproton pump inhibitors yekudzvinyirira acid. CYP2C19 genotype inoshanda se "compass" yekurapa nemishonga.
Sezvo mishonga chaiyo ichigamuchirwa zvakanyanya, huwandu huri kuramba huchiwedzera hwemitemo ine simba iri kusanganisira CYP2C19 genotyping mumashandiro enguva dzose emishonga. Kune varwere, kuziva CYP2C19 genotype yavo kunovabatsira kunzwisisa maitiro avo ega ega emishonga uye kunoita kuti vagone kuita sarudzo pamwe chete nachiremba wavo kuti vagadzire hurongwa hwekurapa hwakakodzera. Kune vanachiremba, kubatanidza mhedzisiro yebvunzo dzemajini muzvisarudzo zvekunyora mishonga inzira ine simba yekuvandudza mhando yekurapa uye kuona kuchengetedzeka kwemurwere.
Macro & Micro-Test'sMhinduro yeCYP2C19 Genotyping
Macro & Micro Test inopa kit yeCYP2C19 genotyping yakavakirwa pahurongwa hwakavandudzwa hwe amplification refractory mutation system (ARMS) yakasanganiswa neTaqman probes ine zvinotevera:
-Kufukidzwa kwakazara kweallele- inoonaCYP2C192, *3, uye *17pasina kupotsa makiyi akasiyana.
-Kudzora kwemhando yakasimba- inosanganisira kudzora kwakaipa/kwakanaka, kudzora kwemukati, uye enzyme yeUDG yekudzora mhando yemazinga mana kuti ive nechokwadi chekuti mhinduro dzakarurama.
-Kubvisa otomatiki- inoenderana neMacro & Micro-Test's fully automated nucleic acid extractor, zvichivandudza mashandiro ebasa.
-Kuenderana kwakafara- inoshanda nemidziyo yePCR inoshanda panguva chaiyo pamusika, kusanganisira ABI 7500 Hongshi SLAN 96P.
-Dudziro yemhedzisiro otomatiki- software yakatsaurirwa yekuongorora (paABI 7500, SLAN 96P, nezvimwewo) inobvumira kududzira otomatiki mhedzisiro, zvichiwedzera kushanda zvakanaka.
-otomatiki yakagadzirira yePOCT- HWTS AIO800 Inoongorora Zvizere zveNucleic Acid Amplification Analyzer inogonesa kushanda kwe "sample in, result out".
Nekufambira mberi kuri kuramba kuchiita pharmacogenomics, CYP2C19 genotyping inotarisirwa kubatsira varwere vakawanda, ichichinja mushonga chaiwo kubva papfungwa kuenda kumabasa ekurapa akajairika. Gwaro idzva reCERSI PGx rinosimbisa basa rakakosha rekuongororwa kweCYP2C19 kwete chete kweclopidogrel asiwo kune runyorwa rwemishonga iri kukura, kusanganisira mishonga inorwisa kushushikana, proton pump inhibitors, uye voriconazole. Kuti zvive nyore kushandisa mishonga inotungamirirwa negenotype, mhinduro dzekuongorora dzakavimbika uye dziri nyore kushandisa dzakakosha. Macro & Micro-Test's pharmacogenomic testing portfolio, ine ruzivo rwakakwana rweallele, kutonga kwakasimba kwemhando, uye mapuratifomu akagadzirira otomatiki, ine chinangwa chekutsigira vanopa hutano mukushandisa mushonga chaiwo uye pakupedzisira kuchengetedza hutano hwevarwere.
Zvigadzirwa Zvakafanana:
Mareferensi:
1. Lima JJ, Thomas CD, Barbarino J, nevamwe. Clinical Pharmacogenetics Implementation Consortium (CPIC) Gwaro reCYP2C19 neProton Pump Inhibitor Dosing. Clin Pharmacol Ther. 2020. doi:10.1002/cpt.20151.
2.Lee CR, Luzum JA, Sangkuhl K, nevamwe. Clinical Pharmacogenetics Implementation Consortium Guideline yeCYP2C19 Genotype uye Clopidogrel Therapy: 2022 Update. Clin Pharmacol Ther. 2022. doi:10.1002/cpt.25261.
3.National Institute for Health and Care Excellence (NICE). Kuongororwa kweCYP2C19 genotype kutungamira kushandiswa kweclopidogrel mushure mekurwara ne ischemic stroke kana kurwiswa kwe ischemic kwenguva pfupi. Gwaro rekuongorora chirwere DG59. Rakaburitswa: 31 Chikunguru 2024.
4. Boka rePrecision Medicine Research Collaboration reChinese Society of Psychiatry. Kubvumirana kwenyanzvi pamusoro pekuongororwa kwemishonga mukurapa kwepfungwa (2025) [Zhonghua Jing Shen Ke Za Zhi].Chinyorwa cheChinese chePsychiatry. 2025;58(6):434-445. doi:10.3760/cma.j.cn11366120240611-00181
5.Dello Russo C, Frater I, Kuruvilla R, nevamwe. Kuyedzwa kweClopidogrel neCYP2C19 genotype: Gwaro rakagadzirwa neUK Centre of Excellence yesainzi yekutonga uye hunyanzvi mu pharmacogenomics (CERSI-PGx). Br J Clin Pharmacol. 2025. DOI: 10.1093/bjcp/…
6.Moriyama B, Owusu Obeng A, Barbarino J, nevamwe. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines yeCYP2C19 neVoriconazole Therapy. Clin Pharmacol Ther. 2017;102(1):45-51. doi:10.1002/cpt.595.
7.Bousman CA, Stevenson JM, Ramsey LB, nevamwe. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline yeCYP2D6, CYP2C19, CYP2B6, SLC6A4, uye HTR2A Genotypes uye Serotonin Reuptake Inhibitor Antidepressants. Clin Pharmacol Ther. 2023;114(1):51-68. doi:10.1002/cpt.2903.
8.Brouwer JMJL, Nijenhuis M, Soree B, nevamwe. Dutch Pharmacogenetics Working Group (DPWG) gwara rekudyidzana kwemajini nemushonga pakati peCYP2C19 neCYP2D6 neSSRIs. Eur J Hum Genet. 2021. doi:10.1038/s41431-021-00894-2.
Nguva yekutumira: Kubvumbi-22-2026