I kēia mau lā aku nei, ua paʻi ka British Journal of Clinical Pharmacology i ke alakaʻi lapaʻau mua i hoʻomohala ʻia e ka UK Center of Excellence for Regulatory Science and Innovation in Pharmacogenomics (CERSI PGx), i kapa ʻia ʻo "CYP2C19 genotype testing for clopidogrel: He alakaʻi i hoʻomohala ʻia e ka UK Center of Excellence for regulatory science and innovation in pharmacogenomics (CERSI PGx)". Ke kālele nei kēia palapala milestone i ka waiwai lapaʻau o ka CYP2C19 genotyping i ke alakaʻi ʻana i ka lāʻau clopidogrel.
E pili ana iā CERSI PGx
ʻO CERSI PGx kekahi o nā kikowaena ʻepekema hoʻoponopono a me nā hana hou ʻehiku i kākoʻo ʻia e ke aupuni UK i hoʻomaka ʻia i Ianuali 2025. I alakaʻi ʻia e ke Kulanui o Liverpool, ua kākoʻo pū ʻia e Innovate UK, ka Medical Research Council (MRC), ka Medicines and Healthcare products Regulatory Agency (MHRA), a me ke Keʻena no nā ʻEpekema Ola (OLS). Manaʻo ke kikowaena e hoʻolalelale i ka hoʻohui palekana a me ka pono o ka pharmacogenomics (PGx) i loko o ka National Health Service (NHS) ma o ka hoʻoponopono ʻana i nā pale hoʻokō koʻikoʻi. ʻO kēia alakaʻi ka alakaʻi lapaʻau mua loa i hoʻopuka ʻia mai ka hoʻokumu ʻia ʻana o CERSI PGx.
No ke aha he mea nui ai ʻo CYP2C19 no Clopidogrel
He lālā koʻikoʻi ʻo CYP2C19 o ka ʻohana enzyme cytochrome P450, kuleana no ka hoʻāla ʻana i ka metabolic a i ʻole ka hoʻopau ʻana i nā lāʻau he nui. ʻO nā polymorphisms genetic i CYP2C19 e alakaʻi i nā ʻokoʻa koʻikoʻi ma waena o kēlā me kēia kanaka i ka metabolism lāʻau, e hoʻopilikia ana i ka pono a me ka palekana.
He mea hoʻohana nui ʻia ʻo Clopidogrel no ka pale ʻana i nā hanana thrombotic i loko o ka maʻi artery coronary, ka hahau ischaemic, ka maʻi artery peripheral, a me ka atrial fibrillation. Ma ke ʻano he prodrug, pono ka clopidogrel i ka hoʻāla metabolic e CYP2C19. Hoʻokaʻawale ke alakaʻi i nā kānaka i nā metabolisers ultrarapid, rapid, normal, intermediate, a me nā metabolisers maikaʻi ʻole e pili ana i ka genotype CYP2C19. ʻAʻole hiki i nā mea lawe o ka nalowale o ka hana alleles (e laʻa, CYP2C192 a me *3*) - nā metabolisers waena a me nā metabolisers maikaʻi ʻole - ke hoʻāla pono i ka clopidogrel, e alakaʻi ana i ka lawa ʻole o ka pale ʻana o ka platelet a me ka hoʻonui ʻia o ka pilikia o ka thrombosis hou.
ʻO ke alapine (pinepine) o ka allele CYP2C192 ma kahi o 15% i nā poʻe ʻEulopa, 30% i nā poʻe ʻAsia Hema, a hiki i ka 60% i nā heluna kanaka ʻōiwi o ke Kai.
Manaʻo Koʻikoʻi: Hoʻāʻo CYP2C19 āpau no Clopidogrel
Ua ʻōlelo ke alakaʻi, me ka nānā ʻole i ka hōʻailona, pono nā maʻi āpau e noʻonoʻo ʻia ai ka clopidogrel e lawe i ka lāʻau lapaʻau.CYP2C19ke kālailai ʻana i nā genotype.Ma muli o nā hopena, pono e hoʻomaikaʻi ʻia ka lāʻau antiplatelet:
-Nā mea hoʻoheheʻe maikaʻi ʻolepono e pale i ka clopidogrel a hoʻohana mua i nā lāʻau lapaʻau ʻē aʻe i hilinaʻi ʻole ʻia i ka metabolism CYP2C19, e like me ticagrelor a i ʻole prasugrel.
-Nā mea hoʻoheheʻe waenapono e noʻonoʻo i nā mea hana ʻē aʻe a i ʻole nā ʻano hana i hoʻoponopono ʻia ma mua o ka hoʻonui wale ʻana i ka nui o ka clopidogrel.
Ma UK, ua ʻae ʻia ka clopidogrel no ka pale ʻana i nā hanana atherothrombotic, no ka hoʻouka kaua ischaemic transient (TIA) a i ʻole ka hahau ischaemic ʻoluʻolu, a no ka pale ʻana i nā hanana atherothrombotic a me thromboembolic i ka atrial fibrillation.
Ma waho aʻe o Clopidogrel: Nā lāʻau lapaʻau ʻē aʻe kahi e koʻikoʻi ai ka CYP2C19 Genotyping
ʻOi aku ka waiwai o ka genotyping CYP2C19 ma mua o clopidogrel. Ma ke ʻano he enzyme metabolizing lāʻau nui, he kuleana koʻikoʻi ko CYP2C19 i ka metabolism o voriconazole, kekahi mau antidepressants, a me nā proton pump inhibitors (PPIs). Paipai nā alakaʻi honua a me nā aupuni he nui i ka genotype i alakaʻi ʻia no kēia mau lāʻau.
1. Nā Lāʻau Hoʻēmi i ka Manaʻo Hoʻohaʻahaʻa (SSRIs)
ʻO nā mea hoʻopaʻa serotonin reuptake koho (SSRIs) - e like me sertraline, citalopram, a me escitalopram - nā mea hana mua no ke kaumaha a ua hoʻopili nui ʻia e CYP2C19. Hoʻoholo pololei ka hana enzyme CYP2C19 i ka nui o kēia mau lāʻau lapaʻau i ka plasma. Loaʻa i nā metabolisers maikaʻi ʻole ka emi ʻana o 30% -60% i ka hoʻomaʻemaʻe lāʻau, kahi e hoʻopilikia ai iā lākou i nā hopena maikaʻi ʻole e like me ka hoʻolōʻihi ʻana o ka manawa QT a me ka hoʻomaha ʻana. Loaʻa pinepine i nā metabolisers Ultrarapid nā nui o ka plasma subtherapeutic, e alakaʻi ana i ka pane lapaʻau lohi a me ka hoʻonui ʻia o ka pilikia o ka hoʻopau ʻana i ka lāʻau.
ʻŌlelo ke alakaʻi o ka 2023 Clinical Pharmacogenetics Implementation Consortium (CPIC) he kiʻekiʻe ka pilikia o ka hoʻolōʻihi ʻana o QT i nā mea hoʻoheheʻe momona maikaʻi ʻole e lawe ana i ka citalopram a i ʻole escitalopram a paipai i ka hōʻemi ʻana o ka nui o ka lāʻau lapaʻau he 50%. ʻŌlelo ke alakaʻi o ka 2021 Dutch Pharmacogenetics Working Group (DPWG) e pono i nā mea hoʻoheheʻe momona maikaʻi ʻole ke loaʻa i ka nui o ka lāʻau lapaʻau escitalopram i hōʻemi ʻia e 50%, a pono i nā mea hoʻoheheʻe momona ultrarapid ke pale aku i ka escitalopram. No ka sertraline, paipai ka DPWG i kahi lāʻau lapaʻau i kēlā me kēia lā ʻaʻole i ʻoi aku ma mua o 75 mg i nā mea hoʻoheheʻe momona maikaʻi ʻole.
ʻO ka mea nui, ʻo ka Chinese Expert Consensus on Pharmacogenomic Testing in Psychiatry (2025) i paʻi ʻia nei - i hoʻomohala ʻia e ka Precision Medicine Collaboration Group o ka Chinese Society of Psychiatry - e hoʻokomo pono ana i nā ʻōlelo paipai no ka genotyping CYP2C19. Hoʻomaopopo ka ʻōlelo kuikahi e hiki ke kuhikuhi ʻia nā ʻōlelo paipai hoʻoponopono dosis mai nā alakaʻi honua e like me CPIC a me DPWG no nā enzymes metabolizing lāʻau (me CYP2C19) no nā heluna kanaka Kina. No laila, ʻo ka genotyping CYP2C19 ma mua o ka hoʻomaka ʻana i ka lāʻau lapaʻau SSRI (e laʻa, escitalopram) e hiki ai ke hoʻonui i ka dosis a i ʻole ke hoʻololi ʻana i nā lāʻau ʻē aʻe i metabolized ʻole ʻia e CYP2C19, no laila e hoʻokō ai i ka mālama pololei, hoʻomaikaʻi i nā helu pane, a me ka hōʻemi ʻana i nā hanana maikaʻi ʻole.
2. Nā mea pale o ka pamu proton (PPI)
Hoʻohana nui ʻia nā mea hoʻopaʻa pamu proton - me ka omeprazole, lansoprazole, a me ka pantoprazole - no nā maʻi e pili ana i ka waikawa e like me ka maʻi reflux gastroesophageal a me nā ʻōpū peptic. Hilinaʻi nui ʻia kā lākou metabolism ma CYP2C19. Hōʻike nā mea maʻi me nā genotypes CYP2C19 like ʻole i ka loli nui i ka pane ʻana i nā PPI. ʻO nā mea lawe o ka nalowale o ka hana alleles (*2, *3) ua hoʻonui nui ʻia ka hōʻike ʻana i ka lāʻau, kahi e hoʻonui ai i ka hoʻopau ʻana i ka waikawa akā hoʻonui pū i ka pilikia o nā hopena maikaʻi ʻole. I ka hoʻohālikelike ʻana, ʻoi aku ka haʻahaʻa o nā metabolisers maʻamau i nā plasma concentrations a hiki ke ʻike i ka hoʻopau ʻana i ka waikawa nāwaliwali, ʻoiai ke mau nei ka loli ma waena o kēlā me kēia kanaka.
ʻŌlelo aʻo ke alakaʻi CPIC 2020 no nā PPI e hoʻopili koke nā mea hoʻoheheʻe ultrarapid e lawe ana i ka omeprazole a i ʻole nā lāʻau like i ka lāʻau lapaʻau, e hopena ana i ka lawa ʻole o ka plasma a me ka hoʻopau ʻana i ka waikawa maikaʻi ʻole. I kēia mau maʻi, pono e hoʻonui ʻia ka nui a nānā ʻia ka pane therapeutic. No nā mea hoʻoheheʻe maikaʻi ʻole, lohi ka hoʻomaʻemaʻe ʻana o ka lāʻau a hiki ke hoʻokiʻekiʻe ʻia nā nui plasma; ʻoiai ʻoi aku ka maikaʻi o ka pono, hoʻonui ʻia ka hiki ke loaʻa ka ʻawaʻawa o ka lāʻau. He mau mea kūpono ka hoʻemi ʻana i ka nui a me ka nānā ʻana i ka pane. No laila, no nā maʻi e hoʻomaka ana i ka lāʻau PPI a i ʻole ka poʻe e ʻike nei i ka pane maikaʻi ʻole a i ʻole nā hopena maikaʻi ʻole, ua ʻōlelo ʻia ka genotyping CYP2C19 e alakaʻi i ka dosing pilikino, hoʻomaikaʻi i ka pono, a hoʻemi i nā hanana maikaʻi ʻole.
3. Voriconazole
He mea hoʻohana antifungal ākea ka Voriconazole i hoʻohana ʻia e mālama i nā maʻi fungal koʻikoʻi e like me ka aspergillosis invasive. He puka makani therapeutic haiki kona: ʻo ka nui o nā plasma kiʻekiʻe e hoʻonui i ka pilikia o ka hepatotoxicity a me nā pilikia ʻike, ʻoiai ʻo nā haʻahaʻa haʻahaʻa e hopena i ka hāʻule ʻana o ka lāʻau. Hoʻopili nui ʻia ka metabolism o voriconazole e CYP2C19, a he hopena koʻikoʻi nā polymorphisms genetic i kona plasma concentration.
Ua paʻi ka CPIC i kahi alakaʻi i hoʻolaʻa ʻia no CYP2C19 a me voriconazole i ka makahiki 2016. Ua ʻōlelo ʻia ua hōʻemi nā metabolisers ultrarapid i nā nui o ka voriconazole a pinepine ʻaʻole hiki ke hoʻokō i nā pae therapeutic i manaʻo ʻia. Loaʻa i nā metabolisers maikaʻi ʻole nā nui o ka trough a me ka nui o ka pilikia o nā hopena maikaʻi ʻole. Hāʻawi ke alakaʻi CPIC i nā ʻōlelo aʻoaʻo dosage kikoʻī e pili ana i ka genotype. No ka laʻana, pono e loaʻa i nā metabolisers ultrarapid makua nā mea hana laina mua ʻē aʻe ʻaʻole i hilinaʻi i ka metabolism CYP2C19, e like me isavuconazole, liposomal amphotericin B, a i ʻole posaconazole. No laila, ʻo ka genotyping CYP2C19 ma mua o ka lāʻau voriconazole e hiki ai i ka dosing pilikino a hoʻemi i ka nui o nā hanana maikaʻi ʻole e pili ana i ka lāʻau.
Ke Koʻikoʻi o ka Lapaʻau: Ke Hoʻolilo nei i ka Lāʻau Lapaʻau i ʻOi aku ka Hilinaʻi
Ke kau hou nei ke alakaʻi i hoʻokuʻu ʻia nei i ka genotyping CYP2C19 ma ke alo o ka lāʻau lapaʻau pololei. Eia nō naʻe, he mea nui e hoʻomaopopo he ʻoi aku ka nui o nā noi lapaʻau o ka genotyping CYP2C19 ma mua o clopidogrel - mai voriconazole (antifungal) a me SSRIs (antidepressants) a hiki i nā mea hoʻopaʻa proton pump no ka hoʻopau ʻana i ka waikawa. Hana ka genotype CYP2C19 ma ke ʻano he "compass" no ka lāʻau lapaʻau.
I ka loaʻa ʻana o ka ʻae ākea ʻia o ka lāʻau lapaʻau pololei, ke hoʻohui nei ka nui o nā alakaʻi mana i ka genotyping CYP2C19 i nā kahe hana lāʻau maʻamau. No nā maʻi, ʻo ka ʻike ʻana i kā lākou genotype CYP2C19 ponoʻī e kōkua iā lākou e hoʻomaopopo i kā lākou ʻano pane lāʻau ponoʻī a hiki ke hoʻoholo like me kā lākou kauka e hoʻomohala i kahi hoʻolālā lapaʻau kūpono. No nā kauka lapaʻau, ʻo ka hoʻohui ʻana i nā hopena hoʻāʻo genetic objective i nā hoʻoholo kuhikuhi he ala ikaika ia e hoʻomaikaʻi ai i ka maikaʻi o ka lāʻau a hōʻoia i ka palekana o ka mea maʻi.
Hoʻāʻo Macro & Micro'sHoʻonā Genotyping CYP2C19
Hāʻawi ʻo Macro & Micro Test i kahi pahu genotyping CYP2C19 e pili ana i kahi ʻōnaehana hoʻololi refractory amplification i hoʻomaikaʻi ʻia (ARMS) i hui pū ʻia me nā probes Taqman me nā hiʻohiʻona aʻe:
-Ka uhi ʻana o ka allele piha- ʻikeCYP2C192, *3, a me *17me ka ʻole o ka nalo ʻana o nā ʻano koʻikoʻi.
-Ka mana maikaʻi paʻa- hoʻokomo pū i nā kaohi maikaʻi ʻole/maikaʻi, kahi kaohi kūloko, a me ka enzyme UDG no ka kaohi maikaʻi ʻehā pae e hōʻoia i nā hopena pololei.
-Ka unuhi ʻakomi– kūlike me ka mea hoʻokaʻawale waikawa nucleic piha piha o Macro & Micro-Test, e hoʻomaikaʻi ana i ka pono o ke kahe hana.
-Hoʻohālikelike ākea- hana pū me nā mea hana PCR manawa maoli ma ka mākeke, me ka ABI 7500 Hongshi SLAN 96P.
-Ka wehewehe ʻana i ka hopena hana aunoa- hiki i ka polokalamu loiloi i hoʻolaʻa ʻia (ma ABI 7500, SLAN 96P, a me nā mea ʻē aʻe) ke wehewehe ponoʻī i nā hopena, e hoʻonui ana i ka pono.
-Hana aunoa mākaukau POCT– Hiki i ka HWTS AIO800 Fully Automated Nucleic Acid Amplification Analyzer ke hana "laʻana i loko, hopena i waho".
Me ka holomua mau o ka pharmacogenomics, manaʻo ʻia ka genotyping CYP2C19 e pōmaikaʻi i ka nui o nā maʻi, e hoʻoneʻe ana i ka lāʻau lapaʻau pololei mai ka manaʻo i ka hana lapaʻau maʻamau. Hoʻoikaika ka alakaʻi CERSI PGx i paʻi hou ʻia i ke kuleana koʻikoʻi o ka hoʻāʻo ʻana o CYP2C19 ʻaʻole wale no clopidogrel akā no ka papa inoa e ulu ana o nā lāʻau lapaʻau, me nā antidepressants, nā mea hoʻopaʻa proton pump, a me voriconazole. No ka hoʻomaʻamaʻa ʻana i ka hoʻohana nui ʻana i ke kuhikuhi ʻana i alakaʻi ʻia e ka genotype, he mea nui nā hoʻonā hoʻāʻo hilinaʻi a maʻalahi hoʻi e hoʻohana. ʻO ka waihona hoʻāʻo pharmacogenomic a Macro & Micro-Test, e hōʻike ana i ka uhi allele piha, ka mana maikaʻi paʻa, a me nā kahua mākaukau automation, e manaʻo e kākoʻo i nā mea lawelawe olakino i ka hoʻokō ʻana i ka lāʻau lapaʻau pololei a me ka palekana hope loa i ke olakino o ka mea maʻi.
Nā Huahana Pili:
Nā Kuhikuhi:
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2.Lee CR, Luzum JA, Sangkuhl K, et al. Ke Alakaʻi Hoʻohui Hoʻokō ʻana o ka Pharmacogenetics Clinical no ka CYP2C19 Genotype a me ka Clopidogrel Therapy: 2022 Update. Clin Pharmacol Ther. 2022. doi:10.1002/cpt.25261.
3.National Institute for Health and Care Excellence (NICE). Ka hoʻāʻo ʻana o ka genotype CYP2C19 e alakaʻi i ka hoʻohana ʻana o clopidogrel ma hope o ka hahau ischemic a i ʻole ka hoʻouka kaua ischemic transient. Alakaʻi Diagnostics DG59. Paʻi ʻia: 31 Iulai 2024.
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6.Moriyama B, ʻOwusu Obeng A, Barbarino J, et al. Nā Alakaʻi Hoʻokō ʻana o ka Clinical Pharmacogenetics (CPIC) no ka CYP2C19 a me ka Voriconazole Ther. Clin Pharmacol Ther. 2017;102(1):45-51. doi:10.1002/cpt.595.
7.Bousman CA, Stevenson JM, Ramsey LB, et al. Ke Alakaʻi Hoʻokō ʻana o ka Clinical Pharmacogenetics (CPIC) no nā Genotypes CYP2D6, CYP2C19, CYP2B6, SLC6A4, a me HTR2A a me nā Antidepressants Serotonin Reuptake Inhibitor. Clin Pharmacol Ther. 2023;114(1):51-68. doi:10.1002/cpt.2903.
8.Brouwer JMJL, Nijenhuis M, Soree B, et al. Ke alakaʻi ʻana o ka Dutch Pharmacogenetics Working Group (DPWG) no ka pilina gene-lāʻau lapaʻau ma waena o CYP2C19 a me CYP2D6 a me SSRIs. Eur J Hum Genet. 2021. doi:10.1038/s41431-021-00894-2.
Ka manawa hoʻouna: ʻApelila-22-2026