462
Title523155901344673106132202
GENETIC15031458018879153232306373416489
POLYMORPHISM20191458018868147214277375455528595681724785883
OF29291458018880153
CYTOCHROME31081458018873140207285358444517596694768
P1-450A239031458018867122159214269324397452
(CYP1A2)43831458018836110177244299373428464
AND48711458018873152232
N-ACETYLTRANSFERASE2-513014580188801171902633374044715386036777508308919641038111111841245131913741410
(NAT2)15031598018837116189251306342
AMONG18691598018873171250330409
EMIRATIS23061598018873171214287360422464526
Faculty5231839013453125196262288321385
Advisor9391839013481154215242290361396
Prof.15031855013861100159194220
Salim17571855013861119144170262
Bastaki20531855013865123172209267322347
Defense5232070013477147178249315363433
Date9872070013477150183253
2615032067013860120
March16582067013884142182232293
201719862067013860120180240
Abstract7504204013481154202235271343414447
Brief15032251013865105130188223
introduction:1760225101382788125164224285346397433459518580619
There24132251013865127185224282
are2729225101385999156
limited2919225101382752144169206264325
studies3278225101385187149210235293342
on36542251013861122
CYP1A238112251013867131191251317377
and42232251013859120181
NAT244392251013874140198258
polymorphisms47312251013862122147202294354394454516541590682731
among54972251013859151211272333
Emiratis.58642251013863156181220276313338387421
Aims:6319225101386792185234273
This15032381013864126151200
study1737238101386299160221276
aims2047238101387196188237
to23192381013849109
determine24622381013874132168226266358384445503
CYP1A229992381013879142203263329389
and34232381013870131192
NAT236502381013886152210270
alleles3954238101387196121179204262311
and43002381013870131192
genotypes45272381013873131192252289343403461510
and50722381013870132193
correlate52992381013863123163202260285343379437
these57712381013849111168217275
genotypes60812381013873131193252289343404462511
with15032511013882107144205
caffeine17432511013861118153188244270331389
metabolism21772511013892150187244305365390415464557
phenotypes27682511013871133190252312348402463521570
among33722511013868161220282343
Emiratis.37492511013872164190229285322347396429
Methods:42132511013895153189251311371420459
After47072511013876111148206245
obtaining49872511013870131167225250312337398459
informed5481251101383596131190229322380440
consent,59562511013861121182231289350387420
five6411251101383969124181
hundred15032641013861123184245285342403
and19402641013858119180
eighty2155264101385883144205242295
one24852641013860121179
non-smoker26982641013862122183223272365424479536576
subjects33082641013849111171203260311348397
were37402641013881139179236
given4011264101386186141198259
300ml43042641013861121181273298
of4637264101386095
caffeinated47662641013851109144178235260321379416474535
soft53352641013849109144181
drink55502641013861101126187242
and58272641013857119180
were60412641013882140179237
asked63122641013858107162219280
to1503277101383796
provide16342771013871111170224249310368
a20362771013868
buccal21392771013871132183233291316
swab24892771013860141198259
and27822771013868130191
a30072771013868
urine31092771013872112137198256
sample33992771013860117210271296354
two37872771013847129188
hours40102771013871131193232281
later.4326277101383593129187227246
TaqMan46062771013874120181266323385
Real50252771013879134192217
Time5277277101387499192250
PCR,55612771013871137205239
PCR-RFLP,58342771013871137205240308366420481499
DNA63672771013885159225
sequencing15032901013849107168229287348399424486546
were20842901013898155195252
performed23712901013877135174209268308400458519
to29242901013853113
determine30712901013877135172230269362387448506
CYP1A236112901013883146207267333393
and40382901013874135196
NAT242692901013889155213273
alleles4577290101387499124182207265314
and49262901013873135196
genotypes.51562901013877135196256293346407465514547
Phenotyping57382901013877138196257317354407468493555616
was63882901013898154204
carried15033031013851108148188213271332
out18693031013876137174
by20773031013878132
analysing22433031013874136194219274323348409470
the27473031013853114172
caffeine29543031013867124159194251276337395
metabolites338330310138109167204261322382407432469527576
using39943031013877126151213274
HPLC43023031013890151206271
analysis.46073031013874136193219273322348397430
Results:50713031013885141190251276313362401
We550730310138115169
found57103031013851110172233294
that60383031013853114172209
1.4%,62813031013877110170277311
16.3%15033161013860120153214321
and18583161013874135196
82.3%20893161013876136169229337
of24603161013876111
the26053161013853114172
recruited28123161013855113163203264289326384445
subjects32923161013865126187218276326363412
were37393161013897155195252
slow,4026316101386590150231261
intermediate43213161013842103140198237330387448473531568626
and49813161013874135196
rapid52123161013855111172197258
CYP1A255043161013882146206266332393
metabolisers,593131610138108166203261321381406432481539578627661
respectively.1503329101384097146207265315352377432489514569593
Only21343291013877139164219
1.4%2387329101386397157264
of2686329101386398
the28183291013840102159
subjects30123291013852114174206263314351400
were34503291013881139179236
homozygotes37213291013864124217276325380440500537594644
for4399329101383897137
CYP1A245703291013870133193254320380
mutant49873291013893154191249310347
alleles5368329101386186112170195253302
while57073291013882143169194252
16.1%59933291013864124157217324
were63553291013882140179237
heterozygotes15033421013861119156214253313362416477536573631680
and22093421013858120180
82.5%24163421013860120153213321
were27633421013881139179236
homozygotes30263421013861121213273322377437497533591640
for3701342101382785125
the3860342101382990148
CYP1A240353421013866129190250316376
wild44373421013882107132193
type4664342101382983143201
genotype.48923421013860118180239276330391449482
Therefore,54003421013864126184223281316374414471505
the5939342101382990148
frequency6121342101382766124185246304365416471
of1503355101386095
the1632355101383899157
wild18243551013882107132193
type2052355101383791152210
genotype22963551013862120181241277331392450
CYP1A2*1A/*1A27803551013867131191251317377437497563605666726792
was36073551013881138187
0.8253829355101386194154214274
followed4137355101383695120146205287345406
by45773551013862116
CYP1A2*1A/*1C47283551013867130191251317377437497563605665725791
and55533551013859120181
CYP1A2*1A/*1K,57693551013866130190250316377437497563605665725789823
with15033681013882107144205
frequencies1743368101383978136196258316377428453511560
of23373681013865100
0.1022471368101386598158218278
and27843681013862123184
0.058,3003368101386498158218278311
respectively.33493681013844101150211269319356381436493519573597
The39803681013869131188
degree42033681013865123184224281339
of45763681013865100
phenotype/genotype471036810138661271852463063433964575155576186767377978348879481006
concordance57503681013856116177228287327387445507557615
was64043681013882139188
81.6%.15033811013860120153214321354
The18923811013878139197
CYP1A2*1C/*1C21233811013880143204264330390450510576618679739805
and29623811013872133194
CYP1A2*3/*331903811013880143204264330390450510552612672
genotypes38973811013874132193253290344405462511
showed44433811013863124184265323384
the48623811013850112169
lowest5066381101383999180238287324
phenotype54243811013875136194256315352406467524
status.5983381101386399157194255304338
With63693811013899124161223
regards1503394101384097158216255315365
to1902394101382989
NAT2,20173941013873139198258291
we23343941013882140
found2508394101382786148209270
that2812394101382990148185
78.5%,30233941013860120154214321355
19.1%34043941013860120153214321
and37513941013858120180
2.4%3958394101386093153261
of4245394101386095
the4374394101382990148
subjects45573941013841102163194252303340389
were49723941013882140179237
slow,5243394101384167126208238
intermediate5515394101381779115173213305363424449507544601
and61433941013858119180
rapid6357394101383288149174235
NAT215034071013873139197257
acetylators,17884071013858109166203257282340377436476525558
respectively,2381407101383390139200258308345370425482507562586
with29944071013882107144206
77.4%32274071013860120146206313
being35684071013860118143205266
homozygote38614071013862121214273322377437497534592
or44804071013860100
heterozygote46074071013862119156214254313362417477537573631
for5273407101382887126
NAT254274071013873139197257
mutant57124071013892154190248310346
alleles6086407101385883108166191249298
and64124071013858119180
18.4%15034201013860120153214321
and18584201013855116177
4.2%2069420101385789149256
were23564201013882140179237
heterozygote26274201013858116153210250309358413473533570628
and32894201013854116177
homozygote35004201013858118210270318373434493530588
for4122420101383290130
the4287420101383394152
NAT244704201013873139197257
wild47584201013882107132193
type4986420101383387147205
genotypes,52264201013857115176236273326387445494527
respectively.5788420101383693142203261312349374429486511566589
The64084201013864126184
most15034331013892152201238
common17754331013847106199291351412
genotypes22174331013861119180240276330391449498
found2749433101383189151212273
were30524331013881139179236
NAT2*5B/*7B,33184331013873139197258318378442484545605669702
NAT2*5B/*6A,40504331013873139197257317377442484544604670703
NAT2*7B/*14B47834331013874140198258318378443485545605665730
and55474331013853115175
NAT2*4/*5B57524331013873139198258318378420480540605
with63864331013882107144206
frequencies1503446101383574131192254312373424449507556
of2084446101386095
0.255,2205446101386093153213273307
0.135,2537446101386094154214274307
0.1052870446101386093153213273
and31694461013858119180
0.09,3374446101386094154214247
respectively.3656446101383088137198255306343368423480505560584
The42654461013864126184
degree44744461013861119180219277335
of4834446101386095
phenotype/genotype495544610138611221802413013383914525105526136717327928298829431001
concordance59904461013842102164214274314374432493544602
was15034591013882138187
equal17254591013861121183241266
to2025459101384099
96.2%.21594591013863123156216324357
The25504591013867129187
NAT2*6A/*6A,27714591013876142200260320380446488549609675708
NAT2*6A/*7B,35134591013876142200261321381447489549609674706
NAT2*7B/*7B,42534591013876142201261321381446488548608672705
NAT2*5A/*5B49924591013876142201261321381447489549609674
and57004591013861122183
NAT2*5A/*5A59174591013876142200260321381447489549609675
genotypes15034721013861119180240277330391449498
were20354721013890148187245
found23144721013843102163224285
to26344721013844104
be27724721013869127
associated29334721013866115164224274299357394452513
with34804721013890115152213
the37274721013845106164
lowest3926472101383392174232281318
5-Acetylamino-6-Formylamino-3-Methyluracil/1Methylxanthine42784721013868108171222280317371396454546571633692732792832889947986107911321158121513081333139414541494155415941679173717731835188819141975201520702121214621722214227415034851013885143179241295320374432493530591617678736
(AFMU/1X)22734851013866132189274346388448512554
ratios.28614851013863119156181241290323
Significant32194851013884109170231257286315366424485522
contributions:37754851013874134195232272297358419456481541602651690
The44994851013888149207
majority474148510138115173204264303328365419
of51954851013883117
the53474851013860121179
studied55614851013872109170231256314375
Emiratis59704851013885178203242298335360409
are64144851013881120178
slow1503498101384974134216
NAT217534981013880146204264
acetylators20514981013864115173210263289346383443482532
with26234981013882107144205
implications28634981013831124185210235286343380405465526576
for34734981013841100139
the36474981013843104162
prescription38444981013867106164213264303328389426451511572
of44514981013866101
medications45924981013893151212237287345382407467528577
that52044981013843104162199
are54374981013864104161
metabolised56394981013892150187245305365390416465523583
by62574981013867122
this64134981013843104130179
enzyme.15035111013858119168223315373406
In1944511101383596
addition,20755111013852113174199236261321382415
a25195111013858
small26115111013844136194219245
percentage28845111013861119159209267328365423483541
of3454511101386095
Emiratis35785111013862154179219275312337386
have39935111013861119173230
slow4257511101384469129210
CYP1A244965111013866130190250316376
enzyme49015111013858120168223316373
activity53095111013852103140165220245282336
which56735111013882143169219281
again59835111013857118176201262
should62805111013843105164226251312
be15035241013861119
taken1656524101384199153210272
into1962524101382990127187
consideration21835241013855115176225250311369409464501526586648
when28695241013881143201262
prescribing31655241013865105162211262301327387413474535
medications37385241013893150211236287345382407467528577
that43495241013841102160197
are45805241013862102159
partially47735241013865123163199224282307333388
metabolised51995241013892150187245305365390416465523583
by58175241013865119
this59715241013840102127176
enzyme.61815241013862123172227319377411
In15035371013841102
Emirati16395371013868161186225281318343
population,20175371013867126187249274332368393453515548
the25995371013843104162
frequency2796537101384180137198260318379430484
of33155371013866101
the34505371013843105163
CYP1A2*1A36475371013872136196256322382442502568
and42505371013864125186
NAT2*544705371013880146204264324384
alleles4889537101386489114172197255304
were52345371013882139179236
the55055371013843104162
highest5702537101386792153215272321358
relative60955371013845103128186223248302359
to64895371013843103
other1503550101386096158216255
alleles1793550101385883108166191249298
frequencies.2126550101383574131192253311372423448506555589
Moreover,27495501013885145184242301355412452471
Individuals32545501013841102163188243268329390448473522
who38105501013882143203
carried40475501013851109148188213271332
NAT2*6A/*6A,44135501013874140198258318378444486546606672705
NAT2*6A/*7B,51535501013873139197257317377443485545605670703
NAT2*7B/*7B,58905501013873139197257318378442484544605669702
NAT2*5A/*5B,15035631013873139197257318378444486546606671703
NAT2*5A/*5A,22315631013874140198258318378444486546606672705
CYP1A2*1C/*1C29625631013866129190250316376436496562604664724790
or3778563101385999
CYP1A2*3/*339035631013866129190250316376436496538598658
genotypes46215631013852110171231267321382440489
might51355631013893118179240277
be54375631013861119
at5581563101385895
high5701563101386287148209
risk5945563101383055104159
of6130563101385994
toxicity6259563101382887141166217242279333
with15035761013882107144205
some17435761013863123216273
drugs20515761013875115176237286
and23725761013872134195
some26015761013864123216274
diseases29095761013876101150208266315373422
compared33655761013866125218279336376433494
to38945761013851111
others40395761013875112173231270319
as43935761013873122
these45495761013852113171220278
genotypes48615761013876134195255292345406464513
are54085761013873113170
associated56125761013873122171231282307365401459520
with61665761013897122159220
the64215761013851113171
slowest1503589101384974134216273323359
phenotype18975891013858119177238298335388449507
status.2439589101384682140177238287321
Consequently,27915891013866126188237294355417475536573598653676
genetic35025891013858115177235271297347
testing3884589101383491140177202264325
is4243589101382271
recommended4349589101383694145204297389447508569627688
prior5071589101385898123183222
to5328589101383493
prescribing5456589101385897155204254294319380405467527
medications60155891013892150211236287345381407466528577
that1503602101383798156193
are1730602101385696153
largely1917602101382482121181239264319
metabolized22696021013892150187245305365390416464522583
by28866021013859114
CYP1A230326021013866130190250316376
or3443602101385897
NAT2.35736021013873139197257291
Gap38966021013874131192
filled:412360210138275682107165226265
This44226021013863124149198
is4655602101382372
the4762602101383596154
first495060210138285797146182
detailed51676021013859117154211237262320381
study5582602101384784145206261
of5877602101385893
CYP1A260036021013866129190250316376
and64146021013855117178
NAT215036151013873139197257
alleles1795615101386287112170196253302
and21326151013862123184
genotypes23506151013865123185244281335396454503
among28876151013862154214276336
Emiratis.32586151013866158183223279315341390423
Dissertation4821288017098132193255344389431524566599689773
MOHAMMAD690416024318034848463281299211401280
MAJED20264160243180328424528668
AL-AHMAD275041602431482363204686047849321072
Department690656014684161240319358394506583655691
of1415656014677110
Pharmacology1559656014667139218257369449525602631708787857
and2449656014679151231
therapeutics2713656014636108185223303382459531567595672725
College690816014694170199228305384461
of1184816014677111
Medicine13288160146108185264293370399471548
and1909816014679151231
Health2173816014682159238267303375
Sciences2581816014663139168245317394471523