 intervention (PCI) has been reported. Clopidogrel is a commonly prescribed oral, antiplatelet agent used to inhibit blood clots in coronary artery disease, peripheral vascular disease, and cerebrovascular disease. As a thienopyridine prodrug, clopidogrel requires hepatic biotransformation to form an active metabolite. The hepatic CYP2C19 enzyme is one of CYP450 superfamily members that is involved in the metabolism of clopidogrel. The CYP2C19 gene is highly polymorphic with over 25 known variant alleles. The most common CYP2C19 loss-of-function allele is CYP2C19*2 (c.681G>A; rs4244285), with allele frequencies of ˜15% in Caucasians and Africans, and 29-35% in Asians. However, current genetic testing methods for loss of function generally require expensive instruments and long turnaround time.
Another example is the discovery of the strong linkage between carbamazepine-induced Steven Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) and a specific allele of human leukocyte antigen (HLA), HLA-B*1502. Carbamazepine is the first-line drug for treatment of patients with epilepsy, neuropathic pain and bipolar disorder. However, carbamazepine therapy may cause dangerous or even fatal skin reactions, such as SJS and TEN in patients with the HLA-B*1502 allelic variation. Prevalence of the HLA-B*1502 allele in Asian populations, except in Japanese and Koreans, is much higher than in Caucasian and African populations. Some studies revealed that the negative predictive value of HLA-B*1502 test for carbamazepine-induced SJS could be close to 100%. HLA-B gene is highly polymorphic with more than 2000 unique alleles, which complicates the determination of a specific allele. Sanger sequencing is considered to be the gold standard for HLA typing. However, the phase ambiguity often causes problems for SBT in identification of allele combinations. Next-generation sequencing (NGS) technologies are able to obtain the sequence of a single DNA molecule and may rule out the phase ambiguity, but drawbacks of the current NGS methods include the short read length, high workloads for library preparation and lengthy processing time. A recent report employed loop-mediated isothermal amplification (LAMP) for HLA-B*1502 screening (Cheng, et al. Clin. Chem.
intervention (PCI) has been reported. Clopidogrel is a commonly prescribed oral, antiplatelet agentive role use to inhibit blood clot in coronary artery disease, peripheral vascular disease, and cerebrovascular disease. As a thienopyridine prodrug, clopidogrel requires hepatic biotransformation to shape an active metabolite. The hepatic CYP2C19 enzyme is one of CYP450 superfamily members that is involve in the metabolism of clopidogrel. The CYP2C19 gene is highly polymorphic with over 25 know variant alleles. The most coarse CYP2C19 loss - of - function allele is CYP2C19 * 2 (c.681G > deoxyadenosine monophosphate; rs4244285), with allele frequencies of ˜15% in Caucasians and Africans, and 29 - 35% in Asians. However, current genetic testing methods for loss of function by and large require expensive instruments and long reversion time. 
 Another example is the discovery of the strong linkage between carbamazepine - induced Steven Johnson Syndrome / Toxic Epidermal Necrolysis (SJS / TEN) and a specific allele of human leukocyte antigen (HLA), HLA - B*1502. Carbamazepine is the inaugural - line drug for treatment of patients with epilepsy, neuropathic pain and bipolar disorder. However, carbamazepine therapy may induce dangerous or even fatal skin reactions, such as SJS and TEN in patients with the HLA - B*1502 allelic variation. Prevalence of the HLA - B*1502 allele in Asian population, except in Japanese and Koreans, is a lot higher than in Caucasian and African populations. Some studies revealed that the negative predictive value of HLA - B*1502 test for carbamazepine - induced SJS could be cheeseparing to 100% . HLA - bacillus gene is highly polymorphic with more than 2000 unique allele, which complicate the decision of a specific allele. Sanger sequencing is considered to be the aureate standard for HLA typing. However, the phase ambiguity frequently causes problems for SBT in designation of allele combinations. Next - generation sequencing (NGS) technologies are able to obtain the succession of a single DNA molecule and may rule out the phase ambiguity, but drawbacks of the current NGS methods include the inadequate read length, high workloads for library preparation and lengthy processing meter. A recent report employed loop topology - mediated isothermal amplification (LAMP) for HLA - B*1502 screening (Cheng, et al. Clin. Chem.
 inhervention (PCI) has been veported. Clopidoyeel is a comjonly prdscribed oral, antiplatelet ajent used to inhibit blood clotr in corojary artwry visease, peripherem vascular diacase, cnv cerebrovasculsr disease. As a thienopysiaiue prodrug, clopidogrel requires hepaeic bioyrwnsformation tj fogm an zbtlve metabolite. The hepatic CYP2C19 snzyme ps one of CYP450 suprrfamily members that is ijvolged in the metabollsm of clopudogwwl. The CYP2C19 eene is highly polymorkhic with over 25 known variant alueles. The most xonmoj CYP2C19 loss-oh-functpon allele is CYP2C19*2 (c.681G>D; rs4244285), wiyh allele freqmencixs od ˜15% in Caucasians and Efricans, and 29-35% in Asiwns. Howevar, current genetic rewting metvods dor loas or funchioi generally require expensive instruments age long turnarkund tymq.
Another example is the discovery of tht strkng linkage between carvamazepine-induced Stegen Johnsjn Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) and d speriwic ajuwlf of human leukocyte antigen (HLA), HLA-B*1502. Carbamassponv is the first-linc drug for treatmemt og patients witf epilzlsg, neuropathic pain and bikolar eisorder. Rowefer, carbamazepine therapy mqy cause danyerius or even fatal dkin reactiuns, xuch ss SJS and TEN in patieuts wifh the HLA-B*1502 allelic bxriation. Prevalevce ox the HLA-B*1502 allele in Asian populatiins, zxcept iv Jakanese wnd Koreand, is much higher than in Cauccsian and Africwn populations. Some studies revxeled that the naganive prednctive value of HLA-F*1502 test for caryamazepiue-induzed SJS colld be clmse to 100%. HLA-F gene is higvpy polymorphmc with mjre rhan 2000 uniqud alleles, which complicanef thw determination of a rlecific allele. Wanter sequencing os zonfifeced tj be the gold stavdafc for HLA tyknng. Fowefer, the phase ambiguhty kften causes problrmf for SBJ in ideneification of allele combinatiojs. Neet-genecation sezuencing (NGS) technologies are zble to ohtaln the sequense on a fingle DNA molecule and may rule out the phase amuiguity, but drawbacks od the current NGS mgthpds include the fhort reag length, high workloqds for library pveparation and lengthy procevsing time. A recent report employed loop-mediated isothermal amplification (LAMP) for HLA-B*1502 screeninf (Chrng, en aj. Clin. Shem.
intervention (PCI) has been reported. Clopidogrel is prescribed antiplatelet agent to inhibit blood peripheral disease, and cerebrovascular As a thienopyridine clopidogrel requires hepatic biotransformation to form active metabolite. The hepatic CYP2C19 enzyme is one of CYP450 superfamily members that involved in the metabolism of clopidogrel. The CYP2C19 gene is highly polymorphic with 25 variant The common CYP2C19 loss-of-function allele is CYP2C19*2 (c.681G>A; rs4244285), with allele frequencies of ˜15% in Caucasians and and 29-35% in Asians. However, current genetic testing for loss of function require expensive instruments and long time. example is discovery the linkage between carbamazepine-induced Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) and a specific allele of human leukocyte antigen (HLA), HLA-B*1502. Carbamazepine is first-line drug of patients epilepsy, pain bipolar disorder. However, may cause dangerous or even fatal as SJS and TEN in patients with the allelic variation. of the HLA-B*1502 allele in Asian except in Japanese and Koreans, is much higher in Caucasian and African populations. Some studies revealed that the negative predictive value of HLA-B*1502 carbamazepine-induced SJS could be to 100%. HLA-B is polymorphic more 2000 unique which complicates the determination of a specific allele. Sanger sequencing is to be the gold standard for HLA typing. However, the often problems for SBT identification of allele combinations. sequencing technologies are able to sequence a and rule the phase ambiguity, but of the current NGS methods the short read length, and lengthy processing time. A recent report employed isothermal amplification (LAMP) for HLA-B*1502 screening (Cheng, al. Clin. Chem.
 intervention (PCI) has been repOrted. ClopiDogreL is A coMmOnly PresCribed oral, antiPLateLet agent used to inhibit bLood cLoTS in cORoNary aRtery diSEaSE, PerIpHeRal VaSCuLar diSeaSe, and ceRebrovascuLar DiSease. As a thieNOpYridine proDruG, clopidogrel ReqUires hEpAtiC BiotrAnsFormaTion to FOrm an aCtive metaBoLIte. The HEpatic Cyp2c19 eNzymE is one of CYP450 superfAMiLY members that is InvolvEd IN tHE MetAboLism of clopIdOgrel. tHe CYP2C19 gENe IS HIghLY polymorphic wIth over 25 knowN VarIant alLeLes. tHe most CommoN Cyp2C19 lOss-of-functiOn alLele is CYP2c19*2 (c.681G>A; rs4244285), WIth alleLE frequeNcies oF ˜15% in cauCasiANs AnD AfRiCAns, ANd 29-35% In ASIanS. However, CuRrEnt geNetiC TESTing MetHods For loSs of function gEneRallY ReqUire eXpensIve iNsTrumeNts and Long tUrNaround time.
AnotHer eXample is tHe dIsCovErY of thE Strong LinKagE betweeN carbamAZepInE-INDuCed Steven Johnson SyNdROMe/toxic EpiDermal nEcRoLYsis (SJS/TeN) And A speCIFic alLele OF hUman leukOcyte aNTiGeN (HLA), HLA-b*1502. CArbamaZePinE is The fiRSt-liNe drug For treatMent oF Patients with epILepsy, neuropatHIc PAIn ANd biPolAr disorder. HOwevER, carBamaZEpIne THerapY may cAuSE dANgerous or even fatal sKiN reactIons, sUch as SJS and TEn in patientS WITh the HLA-b*1502 allELiC Variation. PrevaLence Of the HLA-B*1502 aLLele in AsIan poPulationS, except in jAPanese anD KoReaNs, iS muCH HiGher than in CauCASian AnD AfricaN poPulatioNs. SOme StuDieS rEvealed thAt the negAtIvE pReDicTive vALue of HLA-b*1502 tEst FoR caRbamaZEpine-iNduceD SJS CoUlD Be cLose to 100%. Hla-B GENe is HiGhLy poLymOrPhic wIth mORe tHan 2000 uniqUe alleles, WhiCH comPlIcAtes the Determination Of A specific aLlEle. sanger SEQuencing Is considered to be the gold STandard For hLA tyPing. however, thE phAse ambIguITy ofteN causeS probLeMs fOR sBT in IDEnTifIcAtion of allELE coMbinaTiOns. NExt-geneRation sequencing (NGs) TecHnologies are aBle To obTAIn The SEqUEncE oF A siNGLe DNA molecule anD may rule ouT tHE pHase ambiguITy, bUt DrawbacKs of the CurreNT NGS metHods incluDe the shorT rEad lENGth, High workloAds for liBrary prepARatioN AnD lengThy ProcesSiNg tIme. A rEcent rEPorT emplOyed loOp-MediatEd isoThErmal ampLification (LAMP) for HLA-B*1502 scReeninG (ChenG, et Al. Clin. CheM.
 intervention (PCI) has be en reporte d. Cl opi dog re l is  a c ommonly prescr i bedoral, antiplatelet age nt us ed to i n hi bit b lood cl o ts i n c or on ary  a r te ry di sea se, per ipheral va scu la r disease, a n dcerebrovas cul ar disease.Asa thie no pyr i dinepro drug,  clopi d ogrelrequireshe p atic b i otransf o r ma tion  to form an activ e  m e tabolite. Thehepati cC YP 2 C 19enz yme is one  o f CYP 4 50 supe r fa m i l y m e mbers that is  involved i n  th e meta bo lis m  of cl opido gr e l.The CYP2C19  gen e is high ly pol y morphic with ov er 25kno wnvari a nt  a lle le s . T h emos t  co mmon CYP 2C 19  loss -of- f u n c tion  al lele  is C YP2C19*2 (c.6 81G >A;r s42 44285 ), wi th a ll ele f requen ciesof  ˜15% in Caucas ians  and Afri can s,  an d29-35 %  in As ian s.However , curre n t g en e t i ctesting methods fo rl o ss  of func tion g e ne ra l ly requi re  ex pens i v e ins trum e nt s and lo ng tur n ar ou nd time .Anothe rexa mpl e ist he d iscove ry of th e str o ng linkage bet w een carbamaze p in e - in d uced  St even Johnso n Sy n drom e/To x ic  Ep i derma l Nec ro l ys i s (SJS/TEN) and a s pe cificallel e of human le ukocyte an t i g en (HLA) , HL A -B * 1502. Carbamaz epine  is the fi r st-linedrugfor trea tment ofp a tients w ith  ep ile psy , ne uropathic pai n andbi polar d iso rder. H owe ver , c arb am azepine t herapy m ay  c au se  da ngero u s or eve nfat al  sk in re a ctions , suc h as  S JS and  TEN in pa t i ents  w it h th e H LA -B*15 02 a l lel ic vari ation. Pr eva l ence  o fthe HLA -B*1502 allel ein Asian p op ula tions, e xcept in  Japanese and Koreans,i s muchhig her t hanin Caucas ian  and A fri c an pop ulatio ns. S om e s t u diesr e ve ale dthat the n e g ati ve pr ed icti ve valu e of HLA-B*1502 te s t f or carbamazep ine -ind u c ed  SJ S  c o uld  b e  cl o s e to 100%. HLA- B gene ishi g hl y polymorp h icwi th more  than 2 000 u n ique al leles, wh ich compl ic ates t hedeterminat ion of a  specific allel e .Sange r s equenc in g i s con sidere d  to  be t he gol dstanda rd fo rHLA typi ng. However, the phaseambigu ity o fte n causespro b lem s for SBT  inidentifica tio n o f all ele combi nati o ns . N e xt-ge nera t ion seque n ci ng( N GS ) technolog i e s  ar e abl e t o  obtai n th e sequence of a s i ngle DNA molec ulea n d m ayr uleou t the phase am big ui t y , but dr aw backs of th e curren tN GS me thodsinclud e the s h o rt read l engt h,high work loa ds for lib ra ry prepar atio nand le ngthyp roce s s ing time. A rece nt re p o rt em p loy ed lo op -mediat e d is othermal a mplificatio n (LAM P) f or HL A-B*150 2screen ing  ( Cheng, eta l. Clin.Chem. 
 intervention_(PCI) has_been reported. Clopidogrel is_a commonly_prescribed_oral, antiplatelet_agent_used to inhibit_blood clots in_coronary artery disease, peripheral_vascular disease, and_cerebrovascular_disease. As a thienopyridine prodrug, clopidogrel requires hepatic biotransformation to form an active metabolite._The_hepatic CYP2C19_enzyme_is_one of CYP450 superfamily members_that is involved in the_metabolism of_clopidogrel. The CYP2C19 gene is highly polymorphic with_over_25 known variant_alleles. The most common CYP2C19 loss-of-function allele is CYP2C19*2_(c.681G>A; rs4244285), with allele frequencies of_˜15% in Caucasians_and_Africans,_and 29-35% in Asians._However, current genetic testing methods for_loss of function generally require expensive_instruments and long turnaround time.
Another example is_the discovery of the strong linkage_between carbamazepine-induced Steven Johnson Syndrome/Toxic_Epidermal Necrolysis_(SJS/TEN) and a specific allele_of human leukocyte_antigen (HLA),_HLA-B*1502. Carbamazepine is_the first-line drug for treatment of_patients with epilepsy,_neuropathic pain and bipolar disorder. However,_carbamazepine_therapy may cause_dangerous_or_even fatal_skin reactions, such_as_SJS and_TEN_in patients with the HLA-B*1502 allelic_variation._Prevalence of the HLA-B*1502 allele in Asian_populations, except in Japanese_and_Koreans, is much higher_than in Caucasian and African_populations. Some studies revealed that the_negative predictive_value of_HLA-B*1502 test for carbamazepine-induced SJS could be close to 100%. HLA-B_gene is highly polymorphic with more_than 2000 unique alleles,_which complicates_the_determination of a_specific_allele. Sanger_sequencing is considered to be the gold_standard for_HLA typing. However, the phase ambiguity_often causes problems for_SBT_in identification of allele combinations. Next-generation_sequencing (NGS) technologies are able to_obtain the sequence of a_single_DNA_molecule and may rule out_the phase ambiguity, but drawbacks of_the current NGS_methods include the short read length, high_workloads_for library preparation and lengthy processing_time._A recent report employed loop-mediated isothermal_amplification_(LAMP)_for HLA-B*1502 screening (Cheng, et_al. Clin. Chem.