PATHOGENETIC ROLE OF ENDOTELIN-1 AND POLYMORPHISM OF ITS RECEPTORS IN DIABETES MELLITUS TYPE 2
S.V. Ziablytsev1, O.P. Chernobrytsev1, D.S. Ziablytsev2, O.O. Starodubska1, Ts.B. Abdriakhimova1
- O.O.Bogomoletz Institute of Physiology of the National Academy of Sciences of Ukraine, Kyiv, Ukraine
- Private Higher Education Establishment Kyiv Medical University, Ukraine
DOI: https://doi.org/10.15407/fz65.02.022
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Abstract
The aim of the study was to determine the pathogenetic role
of endothelin-1 (ET1) and the connection of the rs6842241
polymorphisms of the EDNRA gene and rs5351 of the EDNRB
gene with diabetes mellitus type 2 (DM2T) and its
complications in the cohort of Ukrainian patients. Surveyed
152 patients aged 53.9±8.4 years and 95 people in the control
group. Genetic polymorphisms were determined by real-time
polymerase chain reaction (TaqMan Mutation Detection
Assays Life-Technology; USA). The presence of an association
of elevated blood levels of ET1 (3.7-4.7 times) and NO
(1.4-1.5 times) with disease progression has been shown. The
increase in ET1 level was associated with the development of
retinopathy, nephropathy, determined by microalbuminuria
and glomerular filtration rate, sensory polyneuropathy and
arterial hypertension, and NO – with arterial hypertension and
lower limb macroangiopathy. Endothelin receptor gene polymorphisms
were associated with the development of DM2T:
for rs6842241, an increased risk was associated with a minor
allele A (odds ratio 1.87; 95% confidence interval 1.20-2.92;
P=0.005), for rs5351 with ancestral allele C (odds ratio 1.54;
95% confidence interval 1.05-2.25; P=0.026). The presence of
these alleles was associated with a higher blood level of ET1.
Risk A allele rs6842241 contributed to higher body mass index,
systolic and diastolic pressure and triglyceride level in blood
compared to allele C. Carriers of rs5351 risk allele C were ill
for three years longer, they had higher blood levels of urea and
creatinine, microalbuminuria, as well as a lower glomerular
filtration rate than T allele carriers. Thus, directly influencing
the clinical and laboratory parameters and the development of
complications, the rs6842241 and rs5351 endothelin receptor
genes reduced the severity of DM2T.
Keywords:
diabetes mellitus type 2; complications; endothelin-1; rs6842241 EDNRA gene and rs5351 EDNRB gene.
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