Vuba aha, Ikinyamakuru cy’Ubwongereza cy’Imiti y’Ubuvuzi cyasohoye amabwiriza ya mbere y’ubuvuzi yateguwe n’Ikigo cy’Ubwongereza cy’Ubuhanga mu by’Ubumenyi n’Udushya mu by’Imiti (CERSI PGx), cyitwa “Isuzuma rya CYP2C19 ry’ubwoko bwa clopidogrel: Ubuyobozi bwateguwe n’Ikigo cy’Ubwongereza cy’Ubuhanga mu by’Ubumenyi n’Udushya mu by’Imiti (CERSI PGx)”. Iyi nyandiko y’ingenzi yibanda ku kamaro k’ubuvuzi ka CYP2C19 mu kuvura clopidogrel.
Ku bijyanye na CERSI PGx
CERSI PGx ni imwe mu bigo birindwi by’ubumenyi n’udushya bishyigikiwe na leta y’Ubwongereza byatangijwe muri Mutarama 2025. Iyobowe na Kaminuza ya Liverpool, iterwa inkunga na Innovate UK, Inama y’Ubushakashatsi ku Buganga (MRC), Ikigo gishinzwe kugenzura imiti n’ibicuruzwa by’ubuzima (MHRA), n’Ibiro bishinzwe Ubumenyi bw’Ubuzima (OLS). Iki kigo kigamije kwihutisha uburyo bwo guhuza pharmacogenomics (PGx) mu buryo bwizewe kandi bunoze na Serivisi y’Igihugu y’Ubuzima (NHS) binyuze mu gukemura inzitizi z’ingenzi zishyirwa mu bikorwa. Aya mabwiriza ni yo mabwiriza ya mbere y’ubuvuzi yatanzwe kuva CERSI PGx yashingwa.
Impamvu CYP2C19 ari ingenzi kuri Clopidogrel
CYP2C19 ni ingenzi mu muryango wa enzymes za cytochrome P450, ishinzwe gukora cyangwa guhagarika imikorere y'imiti myinshi. Polymorphisms za genetiki muri CYP2C19 zitera itandukaniro rikomeye hagati y’abantu mu mikorere y’imiti, bigira ingaruka ku musaruro n’umutekano.
Clopidogrel ni umuti ukoreshwa cyane mu gukumira indwara zo mu mitsi itera thrombosis mu mitsi y'umutima, indwara yo gucika kw'imitsi itera ischemic, indwara y'imitsi yo mu gice cy'imbere, no mu mitsi itera atrial fibrillation. Nk'umuti utera imbere, clopidogrel isaba ko CYP2C19 ikora neza. Iri tegeko rishyira abantu mu byiciro by'imashini zikora vuba cyane, zikora vuba, zisanzwe, ziciriritse, n'izikora nabi hashingiwe ku bwoko bwa CYP2C19. Imashini zifata alleles zitakaza imikorere (urugero: CYP2C192 na *3*) - izikora neza zitera thrombosis hagati n'izikora nabi - ntizishobora gukora neza clopidogrel, bigatuma habaho kugabanya bihagije platelet mu maraso no kwiyongera kw'ibyago byo kugabanuka kw'imitsi.
Inshuro ya allele ya CYP2C192 ni hafi 15% mu Banyaburayi, 30% mu Banyaziya y'Amajyepfo, naho 60% mu baturage kavukire bo mu Nyanja ya Ositaraliya.
Inama y'ingenzi: Gupima CYP2C19 kuri Clopidogrel
Amabwiriza avuga ko, uko byagenda kose, abarwayi bose basuzumwa na clopidogrel bagomba guhabwaCYP2C19gukora isesengura ry'imiterere y'ibinyabuzima.Hashingiwe ku bisubizo, uburyo bwo kuvura indwara zifata amaraso mu mitsi bugomba kunozwa:
-Ibikoresho bibi byo gutunganya imikorere y'umubiribagomba kwirinda clopidogrel kandi bagahitamo gukoresha indi miti idashingiye ku mikorere ya CYP2C19, nka ticagrelor cyangwa prasugrel.
-Ibikoresho byo mu rwego rwo hagati mu gutunganya imikorere y'umubiribagomba kandi gutekereza ku bindi biyobyabwenge cyangwa uburyo bwo kuvura bwahinduwe aho kongera gusa igipimo cya clopidogrel.
Mu Bwongereza, clopidogrel yemewe mu gukumira indwara za atherothrombotic, ku ndwara ya ischemic igenda igabanuka kugeza ku ntera iri hagati y’ibitero by’isukari (TIA) cyangwa indwara y’imitsi yo mu bwonko ya ischemic, no mu gukumira indwara za atherothrombotic na thromboembolic mu ndwara za atrial fibrillation.
Uretse Clopidogrel: Indi miti aho CYP2C19 Genotype ari ingenzi cyane
Akamaro ka CYP2C19 genotyping karenze kure clopidogrel. Nk'umuti ukomeye uhindura imikorere y'imiti, CYP2C19 inagira uruhare runini mu mikorere ya voriconazole, imiti myinshi igabanya ubukana bw'imiti, hamwe n'imiti igabanya ubukana bwa proton pump inhibitors (PPIs). Amabwiriza menshi mpuzamahanga n'ay'igihugu atanga inama yo gukoresha iyi miti hifashishijwe ikoranabuhanga.
1. Imiti igabanya ubukana bw'indwara zo kwiheba (SSRIs)
Imiti igabanya ubukana bwa serotonin reuptake inhibitors (SSRIs) – nka sertraline, citalopram, na escitalopram – ni yo miti ya mbere itera kwiheba kandi ahanini ikoreshwa na CYP2C19. Imikorere ya enzyme ya CYP2C19 igena neza ingano y’iyi miti mu maraso. Imiti igabanya ubukana bw’imiti igabanukaho 30%–60%, ibi bikaba byayitera ingaruka mbi nko gutinda kwa QT no kuruhuka. Imiti igabanya ubukana bwa Ultrapid ikunze kugira ingano ya plasma idafite ubuvuzi, bigatuma umuti utinda kuvurwa kandi bikagabanya ibyago byo guhagarika imiti.
Amabwiriza ya Clinical Pharmacogenetics Implementation Consortium (CPIC) yo mu 2023 avuga ko abantu banduye bafata citalopram cyangwa escitalopram bafite ibyago byinshi byo kongera igihe cya QT kandi bagasaba kugabanya dose ya 50%. Amabwiriza ya 2021 Dutch Pharmacogenetics Working Group (DPWG) agira inama ko abantu banduye bagomba kugabanya dose ya escitalopram ku kigero cya 50%, kandi ko abantu bavura vuba cyane bagomba kwirinda escitalopram burundu. Kuri sertraline, DPWG itanga inama ku gipimo cya buri munsi kitarenze 75 mg ku bantu banduye.
Icy'ingenzi ni uko ikinyamakuru cy’Abashinwa cy’impuguke ku isuzuma rya farumasi mu ndwara zo mu mutwe (2025) giherutse gusohoka – cyateguwe n’itsinda ry’ubufatanye mu buvuzi rya Precision Medicine ryo mu muryango w’Abashinwa w’indwara zo mu mutwe – gikubiyemo neza inama zo gusuzuma genotike ya CYP2C19. Itangazo ry’ubwumvikane rivuga ko inama zo guhindura urugero rw’ibipimo ziturutse ku mabwiriza mpuzamahanga nka CPIC na DPWG ku misemburo ihindura imiti (harimo na CYP2C19) zishobora kwifashishwa mu baturage b’Abashinwa. Kubwibyo, gusuzuma genotike ya CYP2C19 mbere yo gutangira ubuvuzi bwa SSRI (urugero, escitalopram) bituma habaho gukoresha neza urugero cyangwa guhindura imiti isanzwe idakoreshejwe na CYP2C19, bityo bigatuma habaho ubuvuzi bunoze, kunoza uburyo bwo gusubiza, no kugabanya ingaruka mbi.
2. Ibikoresho bigabanya ubukana bwa pompe ya protoni (PPI)
Indabyo zigabanya umuvuduko wa proton pump – harimo omeprazole, lansoprazole, na pantoprazole – zikoreshwa cyane mu ndwara ziterwa na aside nka reflux y’igifu n’ibisebe byo mu gifu. Ingufu zikoreshwa mu mikorere yazo zishingiye cyane kuri CYP2C19. Abarwayi bafite ubwoko butandukanye bwa CYP2C19 bagaragaza impinduka zikomeye mu gusubiza PPI. Abafite alleles zo kubura imikorere (*2, *3) bafite ubwiyongere bugaragara bw’imiti, bishobora kongera igabanuka rya aside ariko bikongera ibyago byo kugira ingaruka mbi. Mu buryo bunyuranye, ingirabuzimafatizo zisanzwe zifite ingano ntoya mu maraso kandi zishobora kugira igabanuka rito rya aside, nubwo itandukaniro hagati y’abantu rikomeje kuba rinini.
Amabwiriza ya CPIC yo mu 2020 yerekeye PPI agira inama ko abakoresha imiti igabanya ubukana bw’imiti bafata omeprazole cyangwa indi miti isa nayo bahindura umuti vuba cyane, bigatuma igipimo cy’imiti mu maraso kidahagije kandi aside igabanuka. Muri aba barwayi, igipimo kigomba kongerwa kandi hagakurikiranwa uburyo bwo kuvura. Ku bakoresha imiti igabanya ubukana bw’imiti, isukurwa ry’imiti rigenda buhoro kandi igipimo cy’imiti mu maraso gishobora kwiyongera; mu gihe ubushobozi bwo kuyikoresha bushobora kuba bwiza, ubushobozi bwo kuyikoresha burushaho kwiyongera. Kugabanya igipimo no gukurikirana uburyo imiti ifatwa ni ibintu bikwiye kwitabwaho. Kubwibyo, ku barwayi batangira imiti ya PPI cyangwa abagira ingaruka mbi cyangwa mbi, CYP2C19 genotyping irasabwa kugira ngo iyobore uburyo umuntu akoresha imiti ku giti cye, irusheho kugira akamaro, kandi igabanye ingaruka mbi.
3. Voriconazole
Voriconazole ni umuti urwanya udukoko mu buryo bwagutse ukoreshwa mu kuvura indwara zikomeye z’ibihumyo nka aspergillosis. Ifite uburyo bwo kuvura buto: ubwinshi bukabije bw’ibinure mu maraso byongera ibyago byo kwangirika mu maraso no mu kutabona neza, mu gihe ubwinshi buto butuma umuntu ananirwa kuvura. Ihinduka ry’ibinure mu maraso rya voriconazole ahanini riterwa na CYP2C19, kandi ubwinshi bw’ibinure mu maraso bugira ingaruka zikomeye ku bwinshi bw’ibinure mu maraso.
CPIC yasohoye amabwiriza yihariye kuri CYP2C19 na voriconazole mu 2016. Ivuga ko imiti igabanya ubukana bwa voriconazole mu buryo bwihuse cyane yagabanyije urugero rw’imiti ikoreshwa mu kuvura kandi akenshi ntigera ku rwego rw’ubuvuzi bwihariye. Imiti igabanya ubukana bwayo ifite urugero rw’imiti ikoreshwa mu kuvura kandi ibyago byo kugira ingaruka mbi byiyongera cyane. Ubuyobozi bwa CPIC butanga inama zihariye zo gutanga imiti hashingiwe ku bwoko bw’imiti. Urugero, imiti igabanya ubukana bwa ultrapid mu buryo bwihuse cyane ku bantu bakuru igomba guhabwa indi miti ya mbere idashingiye ku mikorere ya CYP2C19, nka isavuconazole, liposomal amphotericin B, cyangwa posaconazole. Kubwibyo, gukoresha CYP2C19 mu kuvura voriconazole bituma umuntu ahabwa imiti ku giti cye kandi bikagabanya ingaruka mbi ziterwa n’imiti.
Akamaro k'ubuvuzi: Gutuma imiti irushaho kuba iy'ukuri
Amabwiriza mashya yasohotse yongeye gushyira CYP2C19 mu kugena imiterere y’uturemangingo mu buryo bunoze. Ariko, ni ngombwa kumenya ko ikoreshwa rya CYP2C19 mu kuvura rirenza clopidogrel - kuva kuri voriconazole (antifungal) na SSRI (antidepressants) kugeza ku mikorere ya proton pump inhibitors mu kugabanya aside. CYP2C19 mu kuvura imiterere y’uturemangingo ikora nk' "icyitegererezo" mu kuvura imiti.
Uko imiti ivura neza igenda yemerwa cyane, amabwiriza menshi yemewe arimo gushyiramo CYP2C19 mu mikorere isanzwe y'imiti. Ku barwayi, kumenya CYP2C19 yabo bwite bibafasha gusobanukirwa imiterere yabo bwite y'imiti kandi bigatuma bafata ibyemezo hamwe n'umuganga wabo kugira ngo bakore gahunda ikwiye yo kuvura. Ku baganga, gushyira ibisubizo by'ibizamini bya genetiki mu byemezo byo gutanga imiti ni uburyo bukomeye bwo kunoza ireme ry'ubuvuzi no kwemeza umutekano w'umurwayi.
Isuzuma rya Macro na Micro'sIgisubizo cyo Gupima Genotipu ya CYP2C19
Ikizamini cya Macro & Micro gitanga ibikoresho byo gupima imiterere y’umubiri bya CYP2C19 bishingiye ku buryo bwiza bwo kongera imbaraga mu guhindura imiterere y’umubiri (ARMS) hamwe n’ibikoresho bya Taqman bifite ibi bikurikira:
-Uburyo bwose bwo gupima allele- iratahuraCYP2C192, *3, na *17hatabayeho kubura ubwoko bw'ingenzi.
-Igenzura ry’ubuziranenge rihamye– ikubiyemo uburyo bwo kugenzura nabi/bwiza, uburyo bwo kugenzura imbere, na enzyme ya UDG yo kugenzura ubuziranenge bw’urwego rune kugira ngo haboneke ibisubizo nyabyo.
-Gukuramo ibikoresho byikora– ikorana na Macro & Micro-Test's byuzuye automated nucleic acid extractor, ikongera imikorere myiza.
-Guhuza byagutse– ikorana n'ibikoresho bya PCR bigezweho ku isoko, harimo na ABI 7500 Hongshi SLAN 96P.
-Gusobanura ibisubizo byikora– porogaramu yihariye yo gusesengura (kuri ABI 7500, SLAN 96P, nibindi) ituma habaho gusobanura ibisubizo mu buryo bwikora, bikongera imikorere myiza.
-POCT yiteguye gukora ikoranabuhanga– HWTS AIO800 Fully automated Nucleic Acid Amplification Analyser ituma "icyitegererezo cyo kwinjira no gusohora" gikorwa.
Bitewe n’iterambere rihoraho rya pharmacogenomics, CYP2C19 genotype yitezweho gufasha umubare munini w’abarwayi, bigatuma imiti ivura neza iva ku gitekerezo ijya ku ivuriro risanzwe. Amabwiriza mashya ya CERSI PGx ashimangira uruhare runini rwo gupima CYP2C19 atari gusa kuri clopidogrel ahubwo no ku rutonde rw’imiti igenda ikura, harimo imiti igabanya ubukana, imiti igabanya ubukana bwa proton pump, na voriconazole. Kugira ngo horoherezwe gukoresha imiti ikoreshwa mu gutanga imiti hifashishijwe ikoranabuhanga, ibisubizo byizewe kandi byoroshye gukoresha ni ngombwa. Porogaramu yo gupima pharmacogenomic ya Macro & Micro-Test, ifite uburyo bwose bwo gupima allele, kugenzura ubuziranenge bukomeye, hamwe n’uburyo bwo kwitegura gukora, igamije gufasha abatanga serivisi z’ubuvuzi gushyira mu bikorwa imiti ivura neza no kurinda ubuzima bw’abarwayi.
Ibicuruzwa bifitanye isano:
Amareferensi:
1. Lima JJ, Thomas CD, Barbarino J, n'abandi. Ubuyobozi bwa Clinical Pharmacogenetics Implementation Consortium (CPIC) ku gipimo cya CYP2C19 na Proton Pump Inhibitor. Clin Pharmacol Ther. 2020. doi:10.1002/cpt.20151.
2.Lee CR, Luzum JA, Sangkuhl K, n'abandi. Ubuyobozi bw'Ishyirwa mu Bikorwa rya Clinical Pharmacogenetics Consortium kuri CYP2C19 Genotype na Clopidogrel Therapy: Ivugurura rya 2022. Clin Pharmacol Ther. 2022. doi:10.1002/cpt.25261.
3. Ikigo cy'Igihugu cy'Ubuzima n'Ubuvuzi Bwiza (NICE). Isuzuma rya CYP2C19 ryerekana ikoreshwa rya clopidogrel nyuma yo gucika intege mu bwonko cyangwa indwara y'imisemburo y'igihe gito. Ubuyobozi bwo gusuzuma DG59. Byasohotse: 31 Nyakanga 2024.
4. Itsinda ry’Ubushakashatsi ku Buvuzi Bwiza ry’Umuryango w’Abashinwa wita ku Buvuzi bw’Indwara zo mu Mutwe. Impuguke zihuriweho ku isuzuma rya farumasi mu buvuzi bw’indwara zo mu mutwe (2025) [Zhonghua Jing Shen Ke Za Zhi].Ikinyamakuru cy'Abashinwa cy'Ubuvuzi bw'Indwara z'Ubwenge. 2025;58(6):434-445. doi:10.3760/cma.j.cn11366120240611-00181
5.Dello Russo C, Frater I, Kuruvilla R, n'abandi. Gupima ubwoko bwa CYP2C19 kuri clopidogrel: Ubuyobozi bwashyizweho n'Ikigo cy'Ubwongereza cy'Ubuhanga mu kugenzura siyansi n'udushya mu bijyanye n'imiti (CERSI-PGx). Br J Clin Pharmacol. 2025. DOI: 10.1093/bjcp/…
6.Moriyama B, Owusu Obeng A, Barbarino J, n'abandi. Amabwiriza agenga ishyirwa mu bikorwa rya Clinical Pharmacogenetics Consortium (CPIC) kuri CYP2C19 na Voriconazole Ther. Clin Pharmacol Ther. 2017;102(1):45-51. doi:10.1002/cpt.595.
7.Bousman CA, Stevenson JM, Ramsey LB, n'abandi. Ubuyobozi bwa Clinical Pharmacogenetics Implementation Consortium (CPIC) kuri CYP2D6, CYP2C19, CYP2B6, SLC6A4, na HTR2A Genotypes hamwe na Serotonin Reuptake Inhibitor Inhibitor Antidepressants. Clin Pharmacol Ther. 2023;114(1):51-68. doi:10.1002/cpt.2903.
8.Brouwer JMJL, Nijenhuis M, Soree B, n'abandi. Ubuyobozi bw'Itsinda ry'Abadage rishinzwe Pharmacogenetics (DPWG) ku mikoranire y'uturemangingo n'imiti hagati ya CYP2C19 na CYP2D6 na SSRIs. Eur J Hum Genet. 2021. doi:10.1038/s41431-021-00894-2.
Igihe cyo kohereza: 22 Mata 2026