ASSOCIATION BETWEEN THE POLYMORPHISM OF ANGIOTENSIN-CONVERTING ENZYME GENE AND INTERLEUKIN-1 BETA GENE AND THE RESPONSE TO ERYTHROPOIETIN THERAPY IN DIALYSIS PATIENTS WITH ANEMIA
Dzekova-Vidimliski P, Eftimovska-Otovikj N, Nikolov I G, Selim Gj, Rambabova-Bushljetik I, Pushevski V, Karanfilovski V, Matevska-Geshovska N, Dimovski A
*Corresponding Author: Assoc. Prof. Pavlina Dzekova-Vidimliski, MD, PhD, University Hospital for Nephrology, Mother Theresa str 17, 1000 Skopje, R. North Macedonia, Email address: pavlinadzekova@yahoo.com
page: 27
|
|
INTRODUCTION
Recombinant human erythropoietin (rHuEPO) has
been used as a treatment for anemia in patients with chronic
kidney disease for more than 30 years. Chronic kidney
disease is characterized by decreased secretion of endog-
enous erythropoietin from kidneys (1-3). The treatment of
anemia with rHuEPO in dialysis patients lowers the blood
transfusions, increases the patient’s quality of life, and
reduces the risk of cardiovascular morbidity and mortality
(4-7). Based on current recommendations, the treatment of
anemia with rHuEPO in patients on hemodialysis begins
when the value of hemoglobin is lower than 100 g/l (6).
On average, 85% of dialysis patients receive rHuEPO for correction of anemia to achieve a target value of hemoglo-
bin up to 110-120 g/l (8, 9). The initial dose of rHuEPO
is 50-100 IU/kg body weight/three times per week, with
subcutaneous or intravenous administration.
Resistance or reduced response to treatment with
rHuEPO in dialysis patients might be caused by several
factors, such as iron deficiency, vitamin B12/folic acid
deficiency, hypothyroidism, infection-inflammation, in-
adequate dialysis, hyperparathyroidism, malnutrition,
bleeding, and malignancy. Irreversible factors are hemo-
globinopathies and bone marrow diseases (8). The eryth-
ropoiesis resistance index (ERI) evaluates the rHuEPO
responsiveness and is calculated as the weekly rHuEPO
dose per kg of body weight, divided by the hemoglobin
(Hb) concentration in g/dl (10). Resistance to human
erythropoietin is encountered in 5-10% of patients on
hemodialysis (11).
The polymorphism of certain genes could be associ-
ated with erythropoietin resistance during the treatment of
anemia in patients on dialysis (12, 13). Every polymor-
phism has a rsID number (“rs” followed by a number), a
unique label used by researchers and databases to identify a
specific polymorphism. Polymorphism (rs1799752) of the
angiotensin-converting enzyme (ACE) gene is character-
ized by the presence (insertion, I) or absence (deletion, D)
of a 287-bp sequence of DNA (ACE I/D) in intron 16 of
the ACE gene located on the chromosome 17 (17q23) (14).
The angiotensin-converting enzyme is a key enzyme in
the creation of angiotensin II. Additionally, angiotensin II
stimulates the proliferation of erythroid precursors, which
is proven by in vitro models, i.e. it affects erythropoiesis
(15, 16). The genetic cluster for interleukin 1 (IL-1), lo-
cated on chromosome 2 (2q14.1), is presented with IL-1a,
IL-1b, and IL-1RN genes that provide genetic information
on the synthesis of cytokines IL-1alpha, IL-1beta, and
endogenous receptor antagonist IL-1 (17). IL-1beta sup-
presses the endogenous secretion of erythropoietin (18).
The polymorphism of the IL-1b gene is IL-1B-511 C/T
(rs 1143627) (19).
|
|
|
|
 |
Number 27
VOL. 27 (2), 2024 |
Number 27
VOL. 27 (1), 2024 |
Number 26
Number 26 VOL. 26(2), 2023 All in one |
Number 26
VOL. 26(2), 2023 |
Number 26
VOL. 26, 2023 Supplement |
Number 26
VOL. 26(1), 2023 |
Number 25
VOL. 25(2), 2022 |
Number 25
VOL. 25 (1), 2022 |
Number 24
VOL. 24(2), 2021 |
Number 24
VOL. 24(1), 2021 |
Number 23
VOL. 23(2), 2020 |
Number 22
VOL. 22(2), 2019 |
Number 22
VOL. 22(1), 2019 |
Number 22
VOL. 22, 2019 Supplement |
Number 21
VOL. 21(2), 2018 |
Number 21
VOL. 21 (1), 2018 |
Number 21
VOL. 21, 2018 Supplement |
Number 20
VOL. 20 (2), 2017 |
Number 20
VOL. 20 (1), 2017 |
Number 19
VOL. 19 (2), 2016 |
Number 19
VOL. 19 (1), 2016 |
Number 18
VOL. 18 (2), 2015 |
Number 18
VOL. 18 (1), 2015 |
Number 17
VOL. 17 (2), 2014 |
Number 17
VOL. 17 (1), 2014 |
Number 16
VOL. 16 (2), 2013 |
Number 16
VOL. 16 (1), 2013 |
Number 15
VOL. 15 (2), 2012 |
Number 15
VOL. 15, 2012 Supplement |
Number 15
Vol. 15 (1), 2012 |
Number 14
14 - Vol. 14 (2), 2011 |
Number 14
The 9th Balkan Congress of Medical Genetics |
Number 14
14 - Vol. 14 (1), 2011 |
Number 13
Vol. 13 (2), 2010 |
Number 13
Vol.13 (1), 2010 |
Number 12
Vol.12 (2), 2009 |
Number 12
Vol.12 (1), 2009 |
Number 11
Vol.11 (2),2008 |
Number 11
Vol.11 (1),2008 |
Number 10
Vol.10 (2), 2007 |
Number 10
10 (1),2007 |
Number 9
1&2, 2006 |
Number 9
3&4, 2006 |
Number 8
1&2, 2005 |
Number 8
3&4, 2004 |
Number 7
1&2, 2004 |
Number 6
3&4, 2003 |
Number 6
1&2, 2003 |
Number 5
3&4, 2002 |
Number 5
1&2, 2002 |
Number 4
Vol.3 (4), 2000 |
Number 4
Vol.2 (4), 1999 |
Number 4
Vol.1 (4), 1998 |
Number 4
3&4, 2001 |
Number 4
1&2, 2001 |
Number 3
Vol.3 (3), 2000 |
Number 3
Vol.2 (3), 1999 |
Number 3
Vol.1 (3), 1998 |
Number 2
Vol.3(2), 2000 |
Number 2
Vol.1 (2), 1998 |
Number 2
Vol.2 (2), 1999 |
Number 1
Vol.3 (1), 2000 |
Number 1
Vol.2 (1), 1999 |
Number 1
Vol.1 (1), 1998 |
|
|
