INFLUENCE OF POTENTIAL GENE POLYMORPHISMS
ON PROPOFOL DOSAGE REGIMEN IN PATIENTS
UNDERGOING ABDOMINAL HYSTERECTOMY
Ivanov E, Sterjev Z, Budic I, Nojkov J, Karadzova D, Sivevski A
*Corresponding Author: Emilija Ivanov, Prim. M.Med., University Clinic for Gynecology and Obstetrics,
University “Ss Cyril and Methodius” Medical Faculty, Mother Theresa, Skopje, Republic of North
Macedonia. Tel./Fax: +389-(0)-23-228-440. E-mail: emilijaivanov@gmail.com
page: 41
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RESULTS
The frequencies of the individual genotypes for each
of the polymorphisms examined are given in Table 1. The
distribution of all three genetic variants was within the
Hardy-Weinberg equilibrium. There was no significant difference
(p >0.05) in the allelic frequencies of the CYB2B6,
GABRA1 and ABCB1 gene variants and genotype distributions
between adult and older patients and between patients
of different ethnicities. Statistically significant differences
were not found in the doses of propofol needed for both
the induction in anesthesia (p = 0.8) and for the additional
doses of propofol needed during the anesthesia (p = 0.46)
among patients with different CYP2B6 (c.516G>A) genotypes.
The doses of propofol used for the induction of
anesthesia were 144.7, 140.6 and 132 mg, respectively,
while additional doses of propofol administered during
the anesthesia were 129.3, 146.7 and 123.3 mg, for patients
with the GG, GA, and AA genotypes, respectively
(Table 2). The results of our study showed no statistically significant difference on the induction time (p = 0.59) and
awakening time (p = 0.06) between patients with different
CYP2B6 (c.516G>A) genotypes, although there was a
trend of shorter time for both parameters in patients with
an A allele. The longest induction and awakening times
were recorded in patients with GG genotype (96.7 and
15.4 seconds, respectively), followed by patients with GA
(73.75 and 12.6 seconds, respectively) and AA genotypes
(54.0 and 11.0 seconds, respectively) (Figure 1).
The results on the possible influence of the GABRA1
(c.1059+15G>A) polymorphism on the doses for induction
and maintenance of anesthesia and times for induction and
awakening showed no statistically significant difference (p
>0.05 for all comparisons). On average, patients with the
GG genotype received 141 mg of propofol, whereas the
average doses for patients with the AG and AA genotype
were 138.9 and 152.2 mg, respectively (p = 0.45) (Table 2).
No statistically significant differences were observed
in the doses of propofol on induction and awakening times
between patients with different GABRA1 (c.1059+15G>A)
genotypes (p = 0.54 and p = 0.7, respectively) (Figure
2). Regarding the ABCB1 (c.3435T>C) polymorphism,
it was observed that the doses of propofol used for the
intravenous anesthesia in patients with the TT genotype
(134.0 mg) were lower than the doses administered to
patients with CC and CT genotypes (143.2 and 146.7 mg,
respectively). However, this difference did not reach a statistical
significance (p = 0.56) (Table 2). There were also
no statistically significant differences both in the number
of patients who needed additional doses of propofol [12
(52.2%), 10 (45.45%) and 24 (53.3%) patients with TT,
CC and CT genotypes, respectively] and in the doses administered
as intraoperative supplementation [126.7, 130
and 140.4 mg in patients with CC, CT and TT genotypes,
respectively (p = 0.8)]. No differences were observed in
the induction (p = 0.16) and awakening (p = 0.86) times
between patients with different ABCB1 genotypes (60.0,
and 89.5 and 97.8 seconds for induction and 13.7, 14.3
and 14.3 seconds for awakening for patients with TT, CT
and CC genotypes, respectively) (Figure 3).
The most common side effects associated with the use
of propofol in our study group were nausea, vomiting and
level of sedation. We did not find statistically significant
differences among these side effects and different genotypes
for the examined polymorphisms. The frequencies
of these side effects correlated with the different genotypes
as shown in Table 3.
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