INFLUENCE OF THE SCN1A IVS5N + 5 G>A
POLYMORPHISM ON THERAPY
WITH CARBAMAZEPINE FOR EPILEPSY
Sterjev Z1,*, Kiteva G2, Cvetkovska E2, Petrov I2, Kuzmanovski I2, Ribarska TJ3,
Nestorovska KA1, Matevska N1,Trajkovik-Jolevska S3, Dimovski AJ1, Suturkova, Lj1
*Corresponding Author: Zoran Sterjev, M. Sei. Pharm Institute of Pharmaceutical Chemistry, Faculty of
Pharmacy, University “St. Cyril and Methodius,” str. Vodnjanska 17, 1000 Skopje, Republic of Macedonia;
Tel./Fax:+38-923-120-229; E-mail: zost@ff.ukim.edu.mk
page: 19
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RESULTS
The genotypes of drug-resistant and drugresponsive
groups and of control group were in
Hardy-Weinberg equilibrium. The genotypic frequencies
of the polymorphism in all patients were
0.20 for GG, 0.52 for AG and 0.28 for the AA genotype,
respectively (Table 3). In the control group,
the distribution was 0.21, 0.49 and 0.29 for GG, AG
and AA, respectively. There were no signifi cant differences
in the allelic frequencies and genotype distribution
between patients and controls (p = 0.94).
Genotype frequencies in the CBZ-responsive
group were 0.23, 0.47 and 0.30, while those in the
CBZ-resistant patients were 0.15, 0.59 and 0.26 for
the GG, GA and AA, respectively. There were no
statistically signifi cant difference between these
two groups (p = 0.55) (Table 3).
Patients with the AA genotype needed a higher average maintenance dose of CBZ (608 273 mg/
day) than patients with the AG and GG genotypes
(542 241 and 468 241 mg/day, respectively)
(Figure 1). The values modes of CBZ doses were:
394 mg/day for GG, 400 mg/ day for AG and 450
mg/day for AA genotypes. These values were interdependent
[2 = 4.965 >2
4;0;30 = 4.878; = 0.30
and k = (3-1)(3-1) = 4) but the differences were
not statistically signifi cant (p = 0.05). We found a
signifi cant statistical difference when we compared
AA+AG vs. GG genotype (z = 1.57073 >z1– =
1.435; = 0.15) (Table 4).
These results indicate that the likelihood of a
positive response to CBZ therapy at an initial dose
of 400 mg is 41.67, 57.89 and 73.68% in patients
with AA, AG and GG genotypes, respectively.
These differences persist only up to a dose of 1000
mg/day, after which there is no difference between
patients with different genotypes (Figure 2). The total
CBZ plasma concentrations and their correlation
with the patients’ genotype showed interdependence
(x2 = 11.610 >2
10;0;32 = 11.5; = 0.32 and k = (6-1)
(3-1) = 10). Distribution of dose ratios (PDD/DDD)
in patients with different genotypes are presented in
Figure 3.
The ratio of daily doses of CBZ divided by plasma
CBZ levels (dose/level) of patients with the AA
genotype was 24.95 11.08, and 22.09 8.45 and
20.62 8.59 for the AG and GG genotypes, respectively.
These results also showed interdependence
(2 = 11.88 >2
10;0;30 =11.781; =0.30 and k = (6-1)
(3-1) = 10), indicating that the differences were primarily
exerted at the level of target responsiveness.
This was further strengthened by the lack of statistically
signifi cant difference in CBZ plasma levels
between patients with different genotypes treated
with the same CBZ dose (Figure 4).
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