He aha ka pharmacogenomics: he alakaʻi piha, genes, examples, a me nā hoʻāʻo

I kēia mau makahiki i hala iho nei, ua hoʻololi ka lāʻau lapaʻau mai kahi hoʻokahi-nui-kūpono i nā mea a pau i hoʻoholo pono ʻia, a ʻo ka pharmacogenomics kekahi o nā kumu. Ke aʻo nei kēia aʻo Pehea ka hopena o kā mākou mau ʻano genetic i ka pane i nā lāʻau lapaʻau, me ka manaʻo o ke kuhikuhi ʻana i ka lāʻau kūpono, i ka nui kūpono a i ka manawa kūpono.

ʻO kēia hoʻololi paradigm hiki iā mākou ke haʻalele i ka hoʻāʻo a me ka hewa i ke kuhikuhi ʻana a hōʻemi i nā hopena ʻino. ʻAʻole ia he hana liʻiliʻi: ʻO nā hopena maikaʻi ʻole i nā lāʻau lapaʻau he pilikia olakino lehulehu a he kumu nui o ka halemai a me ka make. Hāʻawi ʻo Pharmacogenomics i nā mea hana e wānana i ka pono a me ka palekana o kahi lapaʻau ma mua o ka hoʻomaka ʻana.

He aha ka pharmacogenomics a no ke aha ia mea?

Hoʻohui ka Pharmacogenomics i ka kauka lāʻau lapaʻau (ke aʻo ʻana i nā lāʻau lapaʻau) a me ka genomics (ke aʻo ʻana i nā genes a me kā lākou hana) e hoʻomaopopo i ka hoʻololi ʻana o kekahi mau ʻano DNA a me kā lākou ʻōlelo i ka pane i nā lāʻau lapaʻau. Hiki i kēia ke hoʻoponopono maikaʻi nā lāʻau lapaʻau a me nā dosis e pili ana i ka genetic profile o kēlā me kēia maʻi.

I ka hoʻomaʻamaʻa ʻana, ʻo ia ka neʻe ʻana mai kahi "hoʻokahi nui kūpono i nā mea āpau" i kahi ala pololei. ʻAʻole hana like ka nui o nā lāʻau lapaʻau no kēlā me kēia kanaka. a hiki i kekahi ke hana i nā mea ʻawaʻawa koʻikoʻi i ka poʻe e lawe ana i nā ʻano like ʻole. Me ka ʻike genetic, hiki i nā kauka ke hōʻemi i nā pilikia a hoʻomaikaʻi i nā hopena.

Mai ka lāʻau lapaʻau hoʻokahi a hiki i ka lāʻau lapaʻau pilikino

ʻO ka lāʻau lapaʻau hou e alualu i "ka lāʻau kūpono, ma ke ʻano kūpono, i ka manawa kūpono." No ka hoʻokō ʻana i kēia, pono mākou e noʻonoʻo i ka ʻokoʻa interindividual nui. ʻO ka pane i nā lāʻau lapaʻau e pili ana i ka genetic, epigenetic a me nā mea pili i ke kaiapuni, a ʻokoʻa ka haʻawina o kēlā me kēia ma muli o ka lāʻau lapaʻau.

ʻO kahi hiʻohiʻona paradigmatic ʻo warfarin: ʻo kona ʻano maikaʻi loa i hoʻopaʻa ʻia e nā genetics (CYP2C9, VKORC1) a ma nā ʻano hoʻololi ʻole genetic e like me ka makahiki, ke kāne, ke kaumaha, ka puhi ʻana, a i ʻole nā ​​pilina. Hoʻohui i kēia mau ʻāpana āpau Hoʻomaikaʻi i ka wānana dose a hōʻemi i nā hanana ʻino.

I kēia lā ʻike mākou i kēlā ʻOi aku ma mua o 90% o ka heluna kanaka e lawe ma ka liʻiliʻi i hoʻokahi ʻano pharmacogenetic hiki ke hana ʻia, a he mau haneli o nā lāʻau me nā manaʻo pharmacogenomic i ʻike ʻia e nā mana hoʻoponopono. Hoʻoikaika kēia i ka pono lapaʻau o ka hoʻokomo ʻana i nā genetics i ke kuhikuhi ʻana.

Ke nānā nei i ka wā e hiki mai ana, ʻo ka pharmacogenomics ke kī i ka hoʻoponopono pilikino i nā wahi e like me cardiology, oncology, neurology a i ʻole pulmonology, a hoʻoikaika i ka hoʻomohala ʻana i nā lāʻau lapaʻau hou, palekana a ʻoi aku ka maikaʻi.

Nā Genes, biomarkers a me nā ala e hoʻoholo ai i ka pane

ʻIke pinepine ʻia ka ʻokoʻa genetic e biomarkers e like me ka nucleotide polymorphisms (SNPs). Hiki i kēia mau ʻokoʻa ke hoʻololi i ka metabolizing enzymes, receptors, a transporters, a pēlā hoʻololi i ka pono a i ʻole ka palekana o ka laau.

I ka metabolism (phase I), ka ʻohana o nā enzymes CYP450 wawahi i ka nui o na laau lapaau. Hoʻokumu ʻia kona nomenclature ma ka ʻohana, subfamily, a me ka enzyme (e laʻa, CYP2E1), a ua hōʻike ʻia nā ʻano like ʻole me ka ʻōnaehana "hōkū" (*1, *2, *3…). Hoʻololi nā hoʻololi i kēia mau genes mea hoʻopāpā phenotypes e hoʻoholo i nā pae plasma a me ka pane lapaʻau.

I ka māhele II, glutathione S-transferases, N-acetyltransferases, kū i waho. CGU, sulfotransferases a me methyltransferases e like me TPMT a i ʻole COMT. Hoʻopili ʻia nā ʻano like ʻole o kēia mau enzyme me nā mea ʻawaʻawa. Inā lohi ka hoʻopau ʻana e nā genetics, kahi lāʻau lapaʻau me kahi ākea therapeutic haiki hiki ke hōʻea i nā manaʻo weliweli.

He mea koʻikoʻi nō hoʻi nā pahuhopu lāʻau: polymorphisms i loko o nā genes i helu ʻia no mea hōʻano hoʻololi i kā lākou hana a hōʻike a hoʻololi i ka naʻau a i ʻole ka pilikia o nā hopena ʻino. Pēlā nō, ʻO nā mea halihali ABC e like me P-gp (ABCB1/MDR1) hoʻololi i ka absorption, ka hāʻawi ʻana a me ka hoʻopau ʻana, e pili ana i ka ʻike a me ka pane.

I ka pōkole, wehewehe ʻia ka pane ʻana i nā lāʻau lapaʻau e ka pilina ma waena pharmacokinetics (ADME) y pharmacodynamics, hoʻololi ʻia e ka genetics o ka mea maʻi a, i kekahi manawa, e ka genome tumor ponoʻī i ka oncology.

Metabolism phenotypes: mai ultra-wikiwiki a lohi

Ma muli o ka hana enzyme aggregate, hiki ke hoʻokaʻawale ʻia ke kanaka ultra-wikiwiki, wikiwiki, maʻamau, waena, a lohi paha ka metabolizerʻAʻole "maikaʻi a maikaʻi ʻole" kēia lepili no kēlā me kēia: pili kona pili i ka lāʻau lapaʻau a inā he hana a i ʻole prodrug.

Inā he kanaka lohi ka metabolizer o kahi ala e hoʻopau ai i ka lāʻau lapaʻau, hiki iā lākou ke hōʻiliʻili i nā pae kiʻekiʻe a hōʻike. ʻawahia. ʻO ka mea ʻē aʻe, inā hoʻāla kēlā ala like i kahi prodrug, ʻoi aku ka liʻiliʻi o ka metabolizer lohi. hāʻule hoʻōla. ʻO ia ke kumu e hoʻoponopono ai nā alakaʻi lapaʻau i nā ʻōlelo paipai e pili ana i ka lāʻau a me ka phenotype.

• Ultrafast: hoʻololi a hoʻopau i ka lāʻau lapaʻau me ka wikiwiki loa; hiki paha ke koi aku i nā doses kiʻekiʻe a i ʻole nā ​​​​mea ʻē aʻe inā nalowale ka hopena.
• Kūwaena/lohi: hoʻonui i ka ʻike ʻana i nā lāʻau lapaʻau ikaika; ka pilikia o nā hanana pōʻino a pono e hōʻemi i ka nui a i ʻole e pale i ka lāʻau.
• Normal: ka hana enzyme i manaʻo ʻia; Hoʻopili pinepine ʻia nā dosis maʻamau, ka nānā ʻana i nā kumu non-genetic.

Ma waho aʻe o ka DNA, hoʻololi ʻia ka pane hope e makahiki, wahine, kaumaha, meaʻai, comorbidities a me polypharmacy, hiki iā ia ke hoʻoulu a keʻakeʻa paha i nā ala metabolic a hoʻololi i nā ʻano lāʻau.

Pehea mākou e noiʻi ai: nā genes moho, GWAS, a me nā panela

ʻElua mau hoʻolālā maʻamau no ka ʻike ʻana i nā hui lāʻau gene. ʻO ka mua ka moho haʻawina gene, ka nānā 'ana i ka metabolism, ka lawe 'ana a i 'ole nā ​​genes i mana'o 'ia, 'oi aku ka waiwai a me ka pololei e hō'oia i ka pilina genotype-phenotype.

ʻO ka lua, ʻo ka ʻO GWAS (genome-wide association studies) hoʻohālikelike i nā moʻoʻōlelo ma waena o nā pūʻulu (nā hihia a me nā mana) a ʻike i nā ʻano like ʻole e pili ana i ka pane, ka pono, a i ʻole ka ʻona. Me ka hāʻule ʻana o nā kumukūʻai hoʻonohonoho, Ua alakaʻi kēia mau haʻawina i nā ʻike ma nā wahi therapeutic he nui.

I loko o ka hale hoʻokolohua lapaʻau, ʻo ka genome sequencing holoʻokoʻa (WGS) ka mea ʻenehana kūpono, akā ma muli o ke kumukūʻai ua hoʻohana mua ʻia i kēia manawa. exome (WES) a me nā panela i kuhikuhi ʻia. Loaʻa i kahi panel maikaʻi loa pharmacokinetic a me pharmacodynamic markers, nā ʻano like ʻole me nā hōʻike hana a me ka nui o ka heluna kanaka pono no nā lāʻau lapaʻau maʻamau.

No ka hoʻohālikelike i ka hana, aia nā alakaʻi a me nā kumu ʻike e hōʻiliʻili ai hōʻike lapaʻau a me nā ʻōlelo paipai a i ʻole ke koho ʻana i nā mea ʻē aʻe e pili ana i ka genotype. He mea maʻalahi kēia mau alakaʻi i ka unuhi ʻana i nā hopena hoʻāʻo i nā hoʻoholo lapaʻau hiki ke hana.

Nā hiʻohiʻona lapaʻau kahi e hoʻololi ai nā genetics

Hoʻokumu paʻa ʻia kekahi mau hiʻohiʻona. No ka laʻana, ka klopidogrel He prodrug nona ka bioactivation ma muli o CYP2C19. Hoʻopili ʻia nā ʻano like ʻole nalowale o ka hana hanauna haʻahaʻa o ka metabolite ikaika a ʻoi aku ka maikaʻi ʻole o ka lāʻau lapaʻau; I kēia mau hihia, ʻōlelo ʻia e hoʻololi i kahi mea antiplatelet ʻē aʻe.

ka nā fluoropyrimidines (5-FU, capecitabine) pili i nā ʻano like ʻole DPYD: ʻO ka hoʻemi ʻana i ka hana enzyme e hoʻonui i ka pilikia o ka ʻawaʻawa koʻikoʻi, ʻo ia ke kumu i manaʻo ʻia ai nā alakaʻi he nui hoʻololi hoʻololi a i ʻole nā ​​​​mea ʻē aʻe i nā mea lawe i nā alleles pilikia.

Me nā opioids, hiki i ka loli i nā ala CYP ke hoʻololi i ka hana o nā metabolites ikaika a hoʻonui i ka pilikia o pilikia hanu Inā kiʻekiʻe a haʻahaʻa paha ka metabolism ma muli o ka lāʻau. Hōʻike kēia i ke ʻano o ka hoʻololi ʻana o ka metabolizing phenotype i ke koena pono-pilikia.

ʻO kekahi hihia ʻo ka myopathy me simvastatin: ʻO nā ʻano like ʻole o nā mea lawe hepatic (e laʻa, SLCO1B1) e hōʻemi i ka lawe ʻana a hoʻonui i kona ʻike plasma, i hoʻopili ʻia me pōʻino ʻiʻo a pono e akahele i ke koho a i ʻole ka dosage.

Nā hui ma waena o kekahi mau HLA a me ʻeha ʻili koʻikoʻi e like me ka maʻi Stevens-Johnson a i ʻole ka epidermal necrolysis, a me ka predisposition i hyperthermia kino me nā lāʻau anesthetic ma nā ʻano genetic kikoʻī.

ʻO ka hoʻāʻo ʻana i ka Pharmacogenomic: he aha kāna e loiloi ai a pehea e hana ʻia ai

Hiki ke hana ʻia kahi hoʻāʻo ma ke kohu, ka waha, a i ʻole ke koko. Lawe ke keʻena hana i ka DNA a nānā i nā ʻano like ʻole e pili ana i nā lāʻau i uhi ʻia e nā alakaʻi lapaʻau. ʻAʻole loli nā hopena i ke ola a pau (e mau ana kāu genotype), ʻoiai ua hoʻonui ʻia ka wehewehe ʻana i ka wā e ulu ana nā hōʻike.

Ma ka hana lapaʻau, hōʻike nā hōʻike i nā genes, genotypes, phenotypes (e.g., mea hoʻopāpā waena) a me nā ʻōlelo paipai: hoʻololi i ka nui, koho i kahi ʻokoʻa, a i ʻole e hoʻomau i ka lāʻau me ka nānā ʻana. He mea koʻikoʻi ka hoʻololi ʻana o ka lāʻau i nā manawa a pau he 'oihana mālama ola kino.

Hāʻawi kekahi mau laboratories i nā panela piha no nā poʻe maʻi e loaʻa ana i ka polypharmacy. ʻAe kēia ʻano pale pale aku i nā ʻōlelo kuhikuhi pilikia mai ka hoʻomaka ʻana o ka mālama ʻana, ma mua o ka pane ʻana ma hope o kahi hanana ʻino.

ʻO nā palena a me nā pilikia e pono ai mākou e lanakila

Ke hoʻomau nei nā pale: nele i nā keʻena keʻena kumu kūʻai, nā kūlana kūpono i wehewehe maikaʻi ʻia nā ʻōlelo aʻoaʻo a me nā hōʻoiaʻiʻo, a me kahi ākea o nā poʻe loea i aʻo ʻia e wehewehe i nā hopena.

ʻO kekahi palena maʻamau ʻo ia ka manawa pane: inā hana ʻia nā hoʻokolohua ma hope o kahi hanana ʻino, nalowale kekahi o kā lākou waiwai pale. No laila ke koi ʻana no preemptive models (preventive genotyping) i hoʻohui ʻia i loko o ka mōʻaukala lapaʻau a me nā ʻōnaehana kākoʻo hoʻoholo.

He paʻakikī hoʻi ka nui o ka ʻikepili: hoʻohui, wehewehe a mālama i ka ʻike genomic me ka palekana a me ka low cost pono e hoʻokomo i ka hoʻokele waiwai a me ka hoʻokele ʻikepili.

ʻO ka hope, pono hou aku aʻo lapaʻau a me nā mea hana maʻalahi. E hōʻiliʻili wikiwiki nā mea hōʻike, akā ʻo ka hoʻololi ʻana i nā hoʻoholo lapaʻau maʻalahi ka hana koʻikoʻi i ka hana ʻana i nā lāʻau lapaʻau.

Pharmacogenomics vs. pharmacogenetics: ʻaʻole like lākou.

La pharmacogenetics pili i ka hopena o nā ʻano genes i ka metabolism a me ka pane ʻana i kahi lāʻau. pharmacogenomics Hoʻonui ia i ka nānā ʻana i ka genome holoʻokoʻa a, me ka hoʻololi ʻana i ka DNA, hoʻokomo i nā ʻano o hōʻike gene e hoʻololi i ka pane pharmacological.

Ma ka palapala, ua hoʻohana like ʻia nā huaʻōlelo ʻelua no nā makahiki, akā ua hoʻohui ʻia ka piʻi ʻana o ka genomics a ʻokoʻa pololei loa: ʻO ka pharmacogenetics kahi ʻāpana o ka pharmacogenomics, ʻaʻole kona ʻano like.

I ka manawa e noi ai i kahi ho'āʻo pharmacogenomic

He mea pono loa ia ma mua o ka hoʻomaka ʻana i nā lāʻau lapaʻau me kiʻekiʻe ka pilikia o ka ʻona pili i nā ʻano like ʻole (e laʻa, thiopurines a me TPMT/NUDT15; fluoropyrimidines a me DPYD; carbamazepine a me HLA), ma therapeutic hāʻule i wehewehe ʻole ʻia a i ka wā i hoʻolālā ʻia ai ka polypharmacy.

He kūpono hoʻi ia i nā maʻi i manaʻo ʻia ka nui o nā lāʻau lapaʻau i ka manawa: Pono ka hopena genetic no ke ola a hiki ke nīnau ʻia i kēlā me kēia manawa i hana ʻia kahi ʻōlelo kuhikuhi..

No ka hoʻonui i ko lākou waiwai, pono e hoʻohui ʻia nā hopena i loko o ka moʻolelo olakino uila me nā makaʻala a me nā lula hoʻoholo, a hele pū me ke aʻo ʻana no ka hui mālama ola.

Pharmacogenomics, hoʻokō maikaʻi ʻia, hana ʻo ia ma ke ʻano he papa o ka palekana e hoʻohui i ka hoʻokolokolo lapaʻau, lāʻau lapaʻau maʻamau a me nā makemake maʻi e alakaʻi i ka koho therapeutic maikaʻi loa.

Ke holomua wikiwiki nei nā hōʻike a me ka ʻenehana, a me lākou ka hiki ke loaʻa i kēlā me kēia kanaka kahi lapaʻau i kūpono i ko lākou biology. Me nā hui i hoʻomaʻamaʻa ʻia, nā alakaʻi akaka, a me nā ʻikepili i hoʻohui ʻia, ʻAʻole ʻokoʻa ka ʻōlelo kuhikuhi pololei e lilo i hana maʻamau.