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POPULATION FREQUENCIES AND ASSESSMENT OF THE CONTRIBUTION
OF THE RS1800469 POLYMORPHISM OF THE
TGFВ1 GENE
TO THE
PATHOGENETIC MECHANISM OF MYOPIA AMONG THE POPULATION OF
THE FERGANA VALLEY
Otabek Azizbekovich Ikramov
https://orcid.org/0000-0001-8220-3378
Associate Professor of the Department of Ophthalmology of the Andijan State Medical
Institute, PhD
Azizbek Fazilovich Ikramov
https://orcid.org/0000-0001-8540-7931
Head of the Department of Ophthalmology of the Andijan State Medical Institute, Doctor of
Medical Sciences, Professor
Key words:
Myopia, schoolchildren, genetic factors, polymorphism, population frequencies,
visual acuity.
Relevance of the problem.
In Western and East-West Asia, there is an increase in axial
hyperopia among the young population in the last three decades. Which is caused by
hereditary factors or pregnancy defects.
The genetic determination of myopia was noted in the three-factor theory of Avetisov E.S.
(1995), according to which refractive anomalies are formed with the participation of
environmental factors, conditions of visual activity and hereditary factors. Various studies
have shown that myopia can be inherited in both autosomal dominant and autosomal
recessive patterns. In the former case, the disease manifests itself mainly in adolescence with
a milder clinical course. In the autosomal recessive pattern of inheritance, myopia often
develops at an early age and tends to progress with complications.
Numerous scientific works by ophthalmologists have proven that myopia develops in the
case of a number of genetic diseases accompanied by connective tissue dysplasia, such as
Marfan syndrome, Ehlers-Danlos syndrome, Cohen syndrome, Knobloch syndrome, etc.
And also , in addition to connective tissue pathology, there are a large number of genetic
determinants that determine the predisposition to the development of myopia. For example,
changes in the
ACTC1 gene,
involved in the formation of contractile cells - scleral
myofibroblasts, the
GJD2 gene
associated with the regulation of eyeball growth, the
GRIA4
gene
associated with retinoic acid metabolism, the decrease in
MMP
-
2 expression observed
in myopia
significantly suppresses the decrease in the accumulation of the Iα1 collagen
chain in the sclera [Markosyan G.A., Tarutta E.P., 2016; Zhao F , Zhou Q , 2018; Sun Y ,
Sha Y , 2024] etc. Currently, the search for decisive genetic factors that determine hereditary
predisposition to myopia continues to be a pressing scientific task.
It is known that the formation of biologically active molecules is controlled by genetic
mechanisms underlying the regulation of the expression of the genes encoding them. Gene
expression occurs in the process of implementing the information encoded in the DNA
structure with the formation of an mRNA molecule, then an amino acid sequence of a
protein molecule that performs its intended function.
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In this research, to assess the contribution of genetic predisposition to the development and
course of myopia, we studied Population frequencies and assessment of the contribution of
the rs1800469 polymorphism of the
TGFB1 gene
to the pathogenetic mechanism of myopia
among the population of the Fergana Valley.
The data obtained in the study on the frequency of occurrence of alleles and genotypes of the
rs 1800469 ( C 509 T ) polymorphism of the
TGFB 1 gene,
as well as their distribution
among patients with myopia of varying degrees and among conditionally healthy individuals
of the population sample (control) are presented in the table we compiled.
Table of frequencies of alleles and genotypes of polymorphism
rs 1800469 ( C 509 T ) of the
TGFB 1 gene
in the groups of patients with myopia and
controls
No.
Group
Allele frequency
Genotype frequency
C
T
C/C
C/T
T/T
n
%
n
%
n
%
n
%
n
%
1
Main group
(n = 130)
189 72.69 71
27.31 71
54.62 47
36.15 12
9.23
2
Mild
myopia
(n = 30)
46
76.67 14
23.33 18
60
10
33,33 2
6.67
3
Moderate
myopia
(n = 34)
50
73.53 18
26.47 19
55.88 12
35.29 3
8.82
4
High
myopia
(n = 66)
93
70.45 39
29.55 34
51,52 25
37.88 7
10.61
5
Control
(n=110)
177 80.45 43
19.55 73
66.36 31
28.18 6
5.45
It is known that the frequency of occurrence of polymorphic variants of genes has
population differences [Abdulfattah SY, Salman Alagely H, 2024; Kumar P, Kumar A,
2016]. According to some researchers, the heterozygous genotype "T/C" of the rs1800469
(C509T) polymorphism of the TGFB gene occurs in 43% of the subjects, and the
homozygous genotype "T/T" - in 8% [Grossberg AJ, Lei X, 2018], according to others, the
frequency of the genotypes "C/T" and "T/T" is 47.8% and 19.9%, respectively [Cao H, Zhou
Q, 2014].
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We have shown that the population frequency of occurrence of variant genotypes “C/ T ”
(28.2%) and “T/T” (5.5%) of the rs1800469 ( C 509 T ) polymorphism of the
TGFB gene
in
the Uzbek population is lower than existing estimates of its prevalence among individuals of
Asian and other populations .
Our study showed that the frequency of occurrence of the “wild” allele “C” of the rs1800469
( C 509 T ) polymorphism of the
TGFВ1 gene
among the population of the Fergana Valley
without vision pathology was 80.5% , and the frequency of the mutant allele " T " was
19.5%. In the main group of patients with myopia, the frequency of the mutant allele "T"
was 27.3% and significantly exceeded the control indicator ( χ
2
= 4.0; P = 0.05; OR = 1.5 ).
The intergroup difference in the frequency of the "wild" allele "C" was also reliable (main
group - 72.7%; control group - 80.5%; χ
2
= 4.0; P = 0.05 ). (
Appendix 3.1. A
) .
When assessing the frequency of occurrence of the “T” allele among patients with different
clinical variants of myopia, it was found that in the subgroup of patients with high myopia,
the variant allele was more common (29.5%) than in mild (23.3%) and moderate myopia
(26.5%), but the difference between the subgroups was insignificant (subgroups A and B – χ
2
= 0.2; P = 0.7; OR = 0.8; subgroups A and B – χ
2
= 0.8; P = 0.4; OR = 0.7; subgroups B
and C – χ
2
= 0.2; P = 0.7; OR = 0.9 ) (Tables 3.4, 3.5, 3.6) . The frequency of the “T” allele
in the subgroups of patients with mild and moderate myopia also did not have a reliable
difference with the control group (subgroup A and control – χ
2
= 0.4; P = 0.6; subgroup B
and control – χ
2
= 1.5; P = 0.3), whereas in the subgroup of patients with severe myopia and
the control, a reliable difference in the studied indicator was revealed – χ
2
= 4.6; P = 0.05;
OR = 1.7 ).
Thus, the data from the study of the frequency of occurrence of the variant allele of the
polymorphic
TGFB1
gene ( C 509 T ) in samples of patients with visual impairment and
conditionally healthy individuals indicate an association of the functionally unfavorable
allele “T” with the risk of developing high myopia.
Analysis of the distribution of genotypic variants of the rs1800469 ( C 509 T )
polymorphism of the
TGFВ1 gene
revealed the prevalence of the “C/C” genotype both in
the population control sample (66.4%) and in the group of patients with myopia (54.6%).
The frequency of the “C/C” genotype in the group of patients with myopia was lower than
the control value, but the reliability of this difference was at the trend level (χ
2
= 3.4; P = 0.1;
OR = 0.6).
An indeterminate difference in the frequency of the genotype "C/C" was found between
subgroups of patients with myopia of varying degrees (subgroup A and B – 60.0% and
55.9%; χ
2
= 0.1; P = 0.8; OR = 1.2; subgroup A and B – 60.0% and 51.5%; χ
2
= 0.6; P = 0.5;
OR = 1.2; subgroup B and B – 55.9% and 51.5%; χ
2
= 0.2; P = 0.7; OR = 1.1).
LIST OF USED LITERATURE
1.
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Markosyan G.A., Tarutta E.P., Iomdina E.N., et al. Clinical, functional and
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serum level of TGF-B1 and its genetic polymorphisms (C509T and T869C) with Ischemic
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Gichkun OE, Shevchenko OP, Kurabekova RM, Mozheiko NP, Shevchenko AO.
The rs1800470 Polymorphism of the TGFB1 Gene Is Associated with Myocardial Fibrosis
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10.32607/actanaturae.11469.
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Tereffe W, Schlembach PJ, Woodward WA, Buchholz TA, Smith BD. Association of
Transforming Growth Factor β Polymorphism C-509T With Radiation-Induced Fibrosis
Among Patients With Early-Stage Breast Cancer: A Secondary Analysis of a Randomized
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