
A NEW CLOCK IS RUNNING FOR MULTIPLE MYELOMA:
CIRCADIAN CLOCK PROTEIN-PERIOD 3 (PER-3)
POLYMORPHISM Serin I.1,*, Pehlivan S.2, Demir I.3, Oyacı Y.2, Pehlivan M.3 *Corresponding Author: Istemi Serin, M.D., University of Health Sciences, Istanbul Training and
Research Hospital, Department of Hematology, Org. Nafiz GURMAN Cad., Fatih, 34098
tel.: +90 532 3172393, e-mail: serinistemi@hotmail.com page: 37
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MATERIAL AND METHODS
One hundred fifty patients (over 18 years old), diagnosed
with MM in Hematology Clinic of Gaziantep
University between January 2007 - 2009, and 100 healthy
persons were included in this study. Demographic characteristics,
first-line treatments, clinical scores (Durie-Salmon
stages, ISS score, Eastern Cooperative Oncology Group
(ECOG) score), laboratory variables, status of survival
(overall (OS) and progression-free (PFS)) were recorded.
All patients were suitable for ASCT at first evaluation
and following four courses on bortezomib-cyclophosphamide
and dexamethasone (VCD) at partial remission (PR),
ASCT was carried out. Following 24 months, lenalidomide-
dexamethasone (LD) was used as maintenance.
The genotypes of 4R/4R-5R, 5R/5R and alleles of 4R
and 5R on PER-3 gene of patients with ASCT and healthy
controls; were statistically compared before treatment.
In addition, these genotypes, the effects of on PFS and
OS were investigated. Study approval was obtained from
Gaziantep University Ethics Committee (07-2007/40).
Isolation Method
DNA isolation via peripheral blood leukocytes was
measured by the saline precipitation method [10]. Genotypes
of PER-3 gene polymorphism were studied by polymerase
chain reaction- (PCR) and agarose gel electrophoresis
method [11].
Statistical Analysis
According to the Kolmogorov-Smirnov test, quantitative
variables that fit the normal distribution were shown
as mean±standard deviation, but those that did not fit were
shown as median (minimum and maximum). Comparisons
between qualitative measures expressed as numbers and
percentages (%) were made using Chi-square or Fisher’s
exact tests. Post-hoc analysis was evaluated with Bonferroni
correction for intergroup comparisons. Variables
associated with different gene variants were determined
in the multivariate logistic regression model adjusted for
gender and age. Regression results are shown with odds
ratio (OR) and 95% confidence interval (CI). Hardy Weinberg
Equilibrium (HWE) was performed via the De-Finetti
program (online HWE and Association Testing- Institut
für Humangenetik, Munich, Germany). All analyses were
performed with IBM SPSS version v21.0 (IBM Corp,
Armonk, NY, USA), and a p-value less than 0.05 was
considered statistically significant.
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