579
KLINICKÁ341804001074588109168189242288347
FARMAKOLOGIE709804001074291138211265312372415474533554598
A13288040010753
FARMACIE1403804001074191138210265316336380
/18298040010732
Klin190680400107446583131
Farmakol2057804001074278105179220258305325
Farm.2402804001074178104179195
2026;40(3):176-1802617804001074487128170185229275299342363377414451491521559598643
/33058040010732
www.klinickafarmakologie.cz4568804001076513320121425327329234035839843647950254457164568672477179183988990895196610061045
1761348020012657109164
PŘEHLEDOVÉ341200012660124182256312369444520587645
ČLÁNKY1008200012660115187259327395
Korelace34136001063372108140172214247279
genotypu63636001063768110151181220256296
a948360010638
fenotypu100236001062860102143173212248288
CYP2C19:130636001063271106139172203233249
fenokonverze,157036001062860102143179217259297329365400432449
populační203436001063273109149180222255297314
specifika23643600106316597131149179197233274
a2654360010638
moderní270836001065292132164200241259
sekvenační29823600106316298138170212252285326344
přístupy33423600106326885118150192226263
v3621360010636
personalizované367336001063264100134175216256287305338377414450492523
farmakoterapii421236001062967102157197233272302334370412446464481
Korelace3397800298147279369494560685791915
genotypu130278002981412664065426297589011040
a23907800298127
fenotypu2566780029881207347483570699842981
CYP2C19:359579002971402784105336687889044500780029862
fenokonverze,3391040029882207347484612746885100611271217133014551516
populační1904104002981432814235616267518579971060
specifika301310400298104246372479544626693821948
a33913000298127
moderní51413000298207344486611702840904
sekvenační14671300029810422935949161275287798211221186
přístupy270213000298143233296398485624766886
v33915600298127
personalizované51515600298143269360463600739864928991110312401362148616251750
farmakoterapii23131560029882207296500625753887974109911891313145415191583
Jan3391960013745103167
Soukop,5291960013759123187246309374402
Marek9531960013793152194252312
Pecha,12881960013764120170235293322
Pavel16321960013764121177234264
Anzenbacher19191960013772136188246311376435484549607649
Ústav3392120013371113150203254
farmakologie616212001333285121212265316374400460522547602
Fakultní12422120013353101152213238274334359
nemocnice16242120013362117208268318378403452505
Olomouc21532120013375102162254314374424
a26002120013353
Lékařské26762120013352106158212247291341394
fakulty3094212001333285136197222258312
Univerzity34302120013371131156208262297346371407462
Palackého39152120013359110135188237287341401462
v44002120013353
Olomouci44762120013376102163254315375424449
Cytochrom339255001215797133186230284315369451
P450806255001215399148197
2C1910202550012150105152196
(CYP2C19)123325500121281258255001215510615520125329833915962550012128
hraje1641255001215486133156205
klíčovou186325500121467193136188235287341
roli2221255001213286109131
v23692550012147
metabolismu24332550012182132164212267322345367405486540
mnoha29902550012182136190244291
běžně32982550012156106148202251
užívaných35662550012154961191662133392690012155100144199
léčiv,555269001212474119142190205
včetně778269001214891140173228278
klopidogrelu,1073269001214772126183207263317374406455479534554
antidepresiv16452690012148103135157213263320353402441464512
či2175269001214467
inhibitorů2259269001212479134156213236269322355410
protonové2687269001215689143176229285339386435
pumpy.31392690012157112195251297314
Ačkoli34702690012161104150203227250
je3738269001212474
genotypizace3392830012155104158212243292348371412461504552
genu9082830012155103158211
CYP2C1911362830012155106155200252297338
užitečným1490283001215496118150198242296340423
nástrojem19292830012155101139172203256279328410
personalizované23552830012156106138177231285332354376418471517564618667
medicíny,30382830012182132187210253275329373388
v34432830012147
klinické350728300121467092146168211256304
praxi339297001215688136182205
často561297001214492130163216
naráží7942970012154101133180223245
na10562970012155102
fenomén1175297001212878132186268318372
fenokonverze,1564297001212978133186233285340385433465509558577
kdy21582970012146100147
reálný2322297001213281128150204249
fenotyp2588297001212978132186218267323
(enzymatická2928297001212874129171220303350381404447493541
aktivita)3486297001214793128150198221253301326
pacienta3393110012157105150173223278311359
neodpovídá7163110012156106162219275331378402458506
genetickému12403110012155106161211245268312359407491545
předpokladu.1803311001215790139196253309356381428485539560
Tento2381311001215093149181235
jev2634311001212474122
je2774311001212474
nejčastěji28663110012155106129174222261295344368391
způsoben32743110012143100155194249306357412
lékovými3704311001212474339324001214699146196279301
interakcemi658324001212377109157190237283326374457480
mezi11553240012182132175198
induktory1370324001212377133187233268321354403
a17903240012148
inhibitory1855324001212478132155211234266319352401
CYP22743240012157112165
nebo24563240012155105161216
komorbiditami26893240012147100182237269325348404427459507589612
pacienta.33183240012156104149171220275307355376
Ve37113240012155101
středoevropské339338001213972103152208261311358390443499537582630
populaci9863380012156111166220243290333356
je1358338001212473
distribuce1448338001215678116148180203258312356404
alel1869338001214770119142
charakterizována2028338001214498144176223269303352383406448501547594648695
podprůměrnou27403380012156111166222254308389438470525579632
prevalencí3389338001215688137183231253302357400423
loss-of-function339352001212378116155184241270298327382437481516538592647
alely1004352001214770120143190
*21211352001214190
(cca1319352001212869112159
7–81496352001215095148
%)16563520012178103
a17763520012148
nadprůměrnou18413520012155102158214246301383433465520574628
prevalencí2487352001215688137184232255304359403426
gain-of-function29303520012155103125180211268296325354409464508543565619674
alely3621352001214871120144191
*17339366001214190134
(cca495366001212870114162
296803660012151101
%),7943660012179104123
což939366001214599141
zvyšuje1102366001214394144184238262312
riziko143736600121325699122169222
chybné16823660012145100145203258309
interpretace2013366001212479111160193250283333367416460509
farmakogenetických2545366001212978110194242289343399450505556589612657703754798853
výsledků.3420366001214899138161212269316371391
Konvenční3393800012154106161206255309353407430
PCR7863800012152109161
metody9643800012183132165218274321
detekují13023800012156105138186232287310332
pouze16513800012157112166208257
předem1925380001215688137193243325
definované22673800012156105134160214268314362416466
varianty2750380001214795126149196250282331
a30983800012148
neumožňují31633800012154104158240294336390443467489
tzv.3669380001213377127142
haplotype3393940012154101156179232263312367417
phasing.7723940012156110156194216269323343
Sekvenování1131394001214897143192240294347392439493515
nové16623940012154107153200
generace18783940012155104158207238285328376
(NGS)2270394001212790153200226
a25133940012147
sekvenování2576394001213987133182230284337383429483505
exomu3097394001214995147228281
(WES)33943940012128112160208234
tyto3644394001213280115168
limity339408001212446129152185235
překonávají,591408001215790139186239295343389437461484504
avšak1113408001214894133181228
za1358408001214393
cenu1468408001214594149204
vyšší1689408001214899138176199
interpretační1906408001212378110159192249282331365413458512535
a24594080012148
organizační2525408001215487143190245268311360405459482
náročnosti.30254080012155103135190235290344383417440460
Znalost35034080012155110158181236275308
lokálních339422001212479126175198253276321376
populačních7334220012157113170225249297341396419464519
specifik1270422001213996147193215245271317
a16054220012149
rizik167242200121325699122168
fenokonverze1858422001213080135190238291347393442475520570
je2446422001212474
nezbytným25384220012156106149206253289344390474
předpokladem3030422001215790139196253309356381429486536619
pro3667422001215790145
bezpečnou3394360012157108151208259305360415471
individualizaci831436001212378135158206230287341390413436479528573596
farmakoterapie.1448436001213079111195243290343376425458507563587637657
Klíčová339452001246290118163221273326
slova:692452001244472130183236261
CYP2C19,980453001215610915920525930534813254530012121
farmakogenetika,1374453001212978111195243290344401451507558591614661711732
genotyp,21344530012156107162218251300358378
fenotyp,2540453001213080136191224274332351
fenokonverze,2920453001212979135190238292348394443476521571591
lékové3540453001212374121175222272
interakce,339467001212379111160193242288332381401
sekvenování761467001214090137188238293348396444499522
nové13054670012155110157206
generace,15334670012155106162212245293338387407
personalizovaná19614670012157108141182237293341364387430484531580635683
medicína.26654670012184134192215260282338386407
Genotype-phenotype3394910012468122182240277332392446481542601654714772809863924978
correlation13374910012445103141179233261314351379437496
of1854491001245792
CYP2C19:1966491001245811717322528333438423514910012426
phenoconversion,23974910012460119172232290336393452504555594638666724783810
population-specific3395040012460118178237265318355383441500534578638692738766801830875
characteristics,12345040012445105158196249294333386425452496533561607651678
and19325040012453112172
modern21245040012486144205258297356
sequencing2500504001244396157216269328374402461520
approaches30405040012453113173211270323368428481525
in339518001242786
personalised4465180012459113152196254313366394422465519579
pharmacotherapy10455180012460119172211297350395453490550603642694754806
Cytochrome339535001215899136190235290323377461512
P4508775350012153101150201
2C1911045350012152108156202
(CYP2C19)133253500121291358535001215510815820525930434717045350012128
plays1759535001215781129175214
a20005350012148
key2075535001214796142
role2244535001213387111162
in2432535001212479
the2538535001213388138
metabolism27035350012184134168216273329353376415498
of3228535001215484
many33385350012184132187233
commonly35975350012145991823395490012185141198222271
used639549001215696148206
medicines,8745490012185137195219265289345397437459
including1362549001212480126150206264288344402
clopidogrel,1793549001214569126184208266323381414465490511
antidepressants23335490012149105139162220272330364415455495545602635676
and30395490012149105163
proton3231549001215892148181236293
pump35545490012157114199257
inhibitors.339563001212379134157214237270324357398419
Although785563001216184117173228283339394
CYP2C1912065630012155108158205259304347
genotyping15805630012156106162217250300357381436492
is2099563001212463
a21895630012148
useful2264563001215594144174230253
tool2544563001213387143167
in2738563001212479
personalised28445630012157108141181236292340363386425476533
medicine,34045630012183134191214259282337388407
its33957700121235697
clinical45357700121456891146169213262285
application7555770012149105162186209253301334357411467
is1240577001212361
often1319577001215584120169224
complicated1561577001214598182238262285329378410459516
by20955770012157103
the2216577001213387138
phenomenon23715770012157113163218273357407462517573
of2961577001215584
phenoconversion,30635770012156112162218273318371427473522555595617672728748
in339590001212379
which4385900012173129152197252
the710590001213388139
patient’s8695900012157106138161211267299324360
actual1249590001214893128183231255
phenotype15245900012157113163219274307356414465
(enzymatic2010590001212875131174224308356389412456
activity)2487590001214893128151199223256306333
does28405900012156111162202
not30625900012155111143
correspond3226590001214498131164214253310366421478
to3724590001213387
the339604001213387137
genetically4936040012155105160210242265309357380402449
predicted959604001215789138194217261296344401
phenotype.13776040012156111161216270302351408459478
This18736040012149104127165
phenomenon20556040012157112161216271353403458512567
is2639604001212361
most27186040012182137175209
commonly2944604001214497180262316371394441
caused3402604001214492146184234290
by37106040012156102
drug-drug339618001215688142198229287319373429
interactions785618001212378109158190238282317339393448486
involving1288618001212478124177200248271325381
CYP16866180012157113165
inducers1869618001212377133187231279312351
and22386180012147102157
inhibitors2413618001212377132154210233266319351391
or2821618001215487
by29256180012156102
patient30446180012156105136159208263295
comorbidities.3356618001214597180234267323346402424339632001213356106146167
In534632001212479
Central6416320012158107163195228276300
European9696320012149102135189246298346401
populations,13986320012157113170225249297329352407463502523
the1949632001213388138
distribution2115632001215780119152185208265321354377432487
of2630632001215584
alleles274263200121487295145169220259
is3029632001212462
characterised31196320012145100148180229274309358391415454504561
by37086320012157104
a3396460012148
below-average4046460012156106129184255286333379427459507562611
prevalence1032646001215688137184231254304358402450
of1499646001215583
the1599646001213387136
loss-of-function1752646001212478116155184241269298327381436480514537591645
allele241464600121487193143166215
*22646646001214191
(approximately2754646001212872127184216269314337419466497546569616
7–8%)3387646001215095148225250
and36546460012148102158
an3396600012148103
above-average4626600012148105161208257290338385434467515571622
prevalence1103660001215790140187236259309365410459
of1581660001215584
the1684660001213489139
gain-of-function18426600012156104127183215272301331360416472517552575630686
allele254766000121487195145169219
*172785660001214291134
(approximately2938660001212974130188221275320344427475508557581629
29%),35866600012151101181207226
increasing339674001212379124156206254293316371427
the793674001213388139
risk95967400121325695141
of1127674001215584
misinterpretation12386740012183106145168223256305338395428478511560593616671726
of1991674001215584
pharmacogenetic21026740012157113161193277325370424480531586637670693738
findings.2867674001212955110167190245302340362
Conventional32566740012158111167213262318350373428484532555
PCR3396880012153111164
methods5256880012183134167222278335374
detect9216880012156106140189235270
only12136880012155111134181
predefined1416688001215790140197248277303359409466
variants1904688001214897129153201256288329
and22556880012148103160
do24376880012156111
not25706880012156111143
allow273568800121497295150223
so-called2980688001214095128176224248271321378
haplotype33806880012156104160185240273322380431
phasing.3397020012157114162202225281338359
Next-generation7277020012166117165202230289340396447481530563586642698
sequencing1454702001214091148204255311357380436493
(NGS)1975702001212994160209237
and22417020012148104161
whole-exome24317020012174131186211262295349397451535586
sequencing3046702001214091149204255312357380436493
(WES)35687020012128116166216244
overcome3397160012155102151184228282366416
these777716001213388138178228
limitations,1027716001212346130153186235267290345401440461
albeit1509716001214972129180203236
at1767716001214881
the1869716001213388139
cost2029716001214599138172
of2222716001215584
greater2328716001215688138186219268301
interpretative2650716001212479111161193251284334367416448471520569
and32407160012149104160
organisational3422716001215588143191247270308357339729001213356111166214237
complexity.594729001214598181238262312359383416465482
Knowledge10937290012154111166238262312369425475
of1586729001215584
local1688729001212378123172195
population-specific19017290012157112169224248296328351405461493533589640685708737763808
characteristics27267290012145100148180228273308357390413452485508553593
and33377290012148103160
the3514729001213388138
risk367072900121335695141
of339743001215584
phenoconversion4447430012157113163219274320373429476525557598621676731
is1197743001212362
essential1280743001215090129179235267290338361
for1663743001212984117
the1801743001213388139
safe1961743001213988117168
individualisation2150743001212378135158206230287342390413436475524556579634690
of2861743001215584
pharmacotherapy.29667430012157113161194277325370424457512562595644700747763
Key3397600012462113165
words:5317600012476133171232276302
CYP2C19,861760001215610915920525930534712057600012121
pharmacogenetics,12547600012157113161194278326371425481532588638672695740781802
genotype,20847600012156107162218251300358410430
phenotype,25427600012157113164219275307357415467487
phenoconversion,30577600012157113163219274320374430476526559599622677733754
drug339774001215689144200
interactions,561774001212378111160193241286321344399455494515
next-generation10977740012156106153189217276326382432465514546569624680
sequencing,1798774001214090147202252308353376431487508
personalised23277740012157108141182237293341364387426476533
medicine.28827740012183134191214259282337387408
DECLARATIONS:4068257008648871301662142563043393604124625014570257008514
Declaration406827100874987120141179206244271291333375
of445727100874066
originality:45372710087406888130150192230251271298337356
The406828200853473109
manuscript418828200855891130168195227249266306329
is452828200851744
original45832820085386178117133172205222
and481628200853472112
has49392820085387299
not50502820085387699
been516128200853975110149
published532228200853977117134150177216251291
or406829300853862
submitted414529300852867108167184208234269310
elsewhere.44702930085355381117169209245269305320
Ethical406830600873764107127160198218
principles43003060087427090132165185228249287319
compliance:463330600873173134177197218256298330368387
The406831800853678116
authors420531800853475100142183208238
attest44643180085356087124153179
that466431800852465101126
their481131800852465103121146
study49783180085295595138173
was517331800855389118
approved531231800853577120145186221258301
by406832900854073
the41583290085236399
local42743290085175689124141
Ethical44323290085345898115147182199
Committee464832900854179139198215239265300337
and500232900853373113
is513232900851745
in519432900851656
compliance526732900853169129169187204239278311346
with40683400085537298140
human423634000854081143180221
studies44863400085285596139157195226
and474034000853577119
animal48883400085347695156193212
welfare512834000855391110133170196234
regulations53903400085236110414516420140683510085234080120148
of423535100853960
the43153510085236399
authors’44343510085347397136176200229244
institutions46983510085165684109126150189213231270310338
as505635100853462
well513835100855187104122
as527935100853462
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