DETEKSI VARIASI GENETIK GEN PENYANDI ENZIM PEMETABOLISME ASAM VALPROAT UGT1A6 rs2070959 A>G PADA RESPONDEN SEHAT SUKU JAWA DI INDONESIA
Abstract
Epilepsy is a seizure disease which has a risk of death three times higher in
patients of epilepsy compared to normal people and also has the risk Sudden
Unexpected Death in Epilepsy (SUDEP), which causing sudden death due to
epilepsy. As many as 70% of people with epilepsy can be controlled with an
Antiepileptic drugs (OAE). One of the first line OAE agents in epilepsy theraphy
is Valproic Acid (VA). Valproate monitoring is indispensable for its variability
occurance as the result of drug level taken and drug dosing between each
individual; also monitoring for variability occurance happens by gender, age, and
their genetics. The occurence of polymorphism genetic in metabolizing gene of
Valproic Acid (UGT1A6) as a gene encoding the glucoronidase enzyme is
resulting different drug level in plasma which may effect therapeutic results. This
study aimed to determine the frequency of genetic variations in the UGT1A6
rs207959 A>G in Javanese population. The sample used in this study were stored
as DNA speciment from 100 healthy respondent who included the inclusion
criteria. The analysis was using by Polymerase Chain Reaction-Restriction
Fragment Length Polymorphism (PCR-RFLP) method with forward primary 5’CTT
TAA
GGA
GAG
CAA
GTT
TGA
TG-3’
and
reverse
primary
5’-CCA
CTC
GTT
GGG
AAA
AAG
TC-3’.
The
DNA
from
PCR
amplification
digested
by
NsiI
enzyme
which
cut
on
ATGCA|T
sequences
from
the
DNA
template
resulted
wild
type
AA
(128
and
87
bp)
of
genotypic
variant.
Frequency
variant
of
UGT1A6
gene
rs2070959
A>G
can
not
be
shown
in
this
research.
Some
trials
had
been
executed
for
optimizing
the
cutting
by
increasing
amount
of
enzyme,
time
and
temperature
of
incubation, also DNA concentration. The failure of digestion process in
optimizing PCR-RFLP was confirmed by Direct Sequencing method on two
random samples. Sequencing result showed that there were samples that had
genotype variants of AG (heteroziygous mutants) which had the results of cuts,
128, 87 and 215 bp. Therefore, further research is needed related to the detection
of variations of the UGT1A6 gene rs2070959 A>G using restriction enzymes
other then NsiI in Javanese population.
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