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ABSTRACT
This article discusses the significance of the TLR6 gene in the complications of myeloma, a malignant tumor disease
that develops from bone marrow plasma cells. Studies have shown that increased TLR6 gene expression in myeloma
patients is associated with more severe complications and a worse disease prognosis. This may be due to increased
inflammation in the div and increased activation of the immune system. Understanding the role of the TLR6 gene
may help develop new approaches to the diagnosis, treatment and prevention of myeloma.
KEYWORDS
TLR6 gene, myeloma, complications, prognosis, inflammation, activation of the immune system, diagnosis, treatment,
prevention.
INTRODUCTION
Myeloma is a malignant tumor that develops from
plasma cells in the bone marrow. Complications of
myeloma can include various health problems such as
a weakened immune system, osteoporosis, kidney
damage and others.
Today, multiple myeloma is considered an incurable
disease with inevitable relapses. As a rule, relapses
develop within a year after treatment for myeloma,
each subsequent remission being shorter than the
previous one.
Research Article
SIGNIFICANCE OF TLR6 GENE IN COMPLICATIONS OF MYELOMA
DISEASE
Submission Date:
November 10, 2023,
Accepted Date:
November 15, 2023,
Published Date:
November 20, 2023
Crossref doi:
https://doi.org/10.37547/ijmscr/Volume03Issue11-06
Kakhkharova N.Kh.
Republican Specialized Scientific And Practical Medical Center Of Hematology, Uzbekistan
Kayumov A.A.
Republican Specialized Scientific And Practical Medical Center Of Hematology, Uzbekistan
Journal
Website:
https://theusajournals.
com/index.php/ijmscr
Copyright:
Original
content from this work
may be used under the
terms of the creative
commons
attributes
4.0 licence.
Volume 03 Issue 11-2023
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The survival prognosis depends on the stage at which
multiple myeloma is diagnosed and its type. When
detected at stages I and II, the average life expectancy
is 4-4.5 years, at stage IIIA - about 2.5 years.
The most unfavorable prognosis for multiple myeloma
detected at stage IIIB, the life expectancy of patients is
about 15 months. With primary resistance to
chemotherapy, survival is less than a year.
The TLR6 gene plays an important role in the
development
and
progression
of
myeloma
complications. Multiple studies have shown that the
TLR6 gene is associated with various aspects of the
pathogenesis and complications of myeloma.
One of the main functions of the TLR6 gene is to
regulate the div's immune system. It encodes a
receptor called toll-like receptor 6, which plays a key
role in pathogen recognition and activation of the
immune system. Due to this, the TLR6 gene influences
the development and progression of myeloma.
Some studies have shown that mutations or
polymorphisms of the TLR6 gene may be associated
with an increased risk of developing myeloma
complications. For example, one study found an
association between the presence of certain TLR6
gene variants and more aggressive myeloma.
In addition, the TLR6 gene may influence the
interaction of the tumor with components of the
microenvironment. Some studies indicate that
activation of TLR6 may promote the proliferation and
invasion of myeloma tumor cells, as well as their ability
to suppress the immune response.
More detailed research in this area will help to better
understand the role of the TLR6 gene in myeloma
complications and possible ways to develop new
therapeutic approaches.
The Ser249Pro mutation in the TLR6 gene may be
associated with various diseases, including myeloma.
184 patients with multiple myeloma were examined.
Among them, in the main group n = 94, of which
patients with grade I neuropathy n = 22, grade II
neuropathy n = 44, grade III neuropathy n = 28, in the
control group n = 90. We examined allele frequencies
and genotype frequency distributions. The results are
shown in Table 1.
Num
Group
Allele frequency
Genotype distribution frequency
S
P
S/S
S/P
P/P
n
%
n
%
n
%
n
%
n
%
1
Main group (n =
94)
26
13,8
162
86,2
3
3,19
20
21,3
71
75,5
Volume 03 Issue 11-2023
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5.
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2
Neuropathy
stage I (n = 22)
12
27,3
32
72,7
3
13,6
6
27,3
13
59,1
3
Neuropathy
stage II (n = 44)
8
9,09
80
90,9
0
0
8
18,2
36
81,8
4
Neuropathy
grade III (n = 28)
6
10,7
50
89,3
0
0
6
21,4
22
78,6
5
Control group (n
= 90)
27
15
153
85
4
4,44
19
21,1
67
74,4
Table 1. Frequency of distribution of alleles and genotypes among patients with multiple myeloma
Also in the same study, we examined differences in the
frequency of allelic and genotypic variants of the
Ser249Pro polymorphism in the TLR6 gene in patient
groups. The distribution of genotypes across the
studied polymorphic loci was checked for compliance
with the Hardy
–
Weinberg equilibrium using Fisher's
exact test. Pearson's χ test with Yate’s correction for
continuity was used to compare allele frequencies
between different groups. The results of the study are
shown in Table 2.
Alleles
и
Genotypes
Number of alleles and genotypes
examined
χ2
p
RR
95%CI
OR
95%C
I
Main group
Control group
n
%
n
%
S
26
13,8
27
15,0
0,1
0,80
0,9
0,52 - 1,64
0,9
0,51
- 1,63
P
162
86,2
153
85,0
0,1
0,80
1,1
0,62 - 1,91
1,1
0,61
- 1,97
S/S
3
3,2
4
4,4
0,2
0,70
0,7
0,13 - 3,93
0,7
0,16
- 3,24
S/P
20
21,3
19
21,1
0,0
0,99
1,0
0,51 - 1,98
1,0
0,5 -
2,05
P/P
71
75,5
67
74,4
0,0
0,90
1,0
0,53 - 1,94
1,1
0,54
- 2,07
Volume 03 Issue 11-2023
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SJIF
I
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(2021:
5.
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(2022:
5.
893
)
(2023:
6.
184
)
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–
1121105677
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Alleles
и
Genotypes
Number of alleles and genotypes
examined
χ2
p
RR
95%CI
OR
95%C
I
Neuropathy stage
I
Neuropathy stage
II
n
%
n
%
S
12
27,3
8
9,1
7,5
0,01
3,0
1,21 - 7,42
3,8
1,46
- 9,63
P
32
72,7
80
90,9
7,5
0,01
0,3
0,11 - 0,98
0,3
0,1 -
0,68
S/P
6
27,3
8
18,2
0,7
0,40
1,5
0,36 - 6,26
1,7
0,51
- 5,63
P/P
13
59,1
36
81,8
4,0
0,05
0,7
0,2 - 2,56
0,3
0,1 -
0,98
Alleles
и
Genotypes
Number of alleles and genotypes
examined
χ2
p
RR
95%CI
OR
95%C
I
Neuropathy stage
I
Neuropathy
grade III
n
%
n
%
S
12
27,3
6
10,7
4,6
0,05
2,5
1,11 - 5,84
3,1
1,1 -
8,88
P
32
72,7
50
89,3
4,6
0,05
0,4
0,1 - 1,48
0,3
0,11
- 0,91
S/P
6
27,3
6
21,4
0,2
0,70
1,3
0,34 - 4,8
1,4
0,37
- 5,04
P/P
13
59,1
22
78,6
2,2
0,20
0,8
0,23 - 2,42
0,4
0,12
- 1,34
Alleles
и
Genotypes
Number of alleles and genotypes
examined
χ2
p
RR
95%CI
OR
95%C
I
Neuropathy stage
I
Control group
n
%
n
%
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03
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SJIF
I
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(2021:
5.
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)
(2022:
5.
893
)
(2023:
6.
184
)
OCLC
–
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S
12
27,3
27
15,0
3,7
0,10
1,8
0,6 - 5,52
2,1
0,99
- 4,58
P
32
72,7
153
85,0
3,7
0,10
0,6
0,36 - 0,85
0,5
0,22
- 1,01
S/S
3
13,6
4
4,4
2,5
0,20
3,1
0,48 - 19,64
3,4
0,76
-
15,22
S/P
6
27,3
19
21,1
0,4
0,60
1,3
0,26 - 6,52
1,4
0,48
- 4,06
P/P
13
59,1
67
74,4
2,0
0,20
0,8
0,18 - 3,41
0,5
0,19
- 1,3
Alleles
и
Genotypes
Number of alleles and genotypes
examined
χ2
p
RR
95%CI
OR
95%C
I
Neuropathy stage
II
Neuropathy
grade III
n
%
n
%
S
8
9,1
6
10,7
0,1
0,80
0,8
0,34 - 2,15
0,8
0,27
- 2,54
P
80
90,9
50
89,3
0,1
0,80
1,2
0,33 - 4,15
1,2
0,39
- 3,66
S/P
8
18,2
6
21,4
0,1
0,80
0,8
0,32 - 2,24
0,8
0,25
- 2,66
P/P
36
81,8
22
78,6
0,1
0,80
1,0
0,39 - 2,75
1,2
0,38
- 4,01
Alleles
и
Genotypes
Number of alleles and genotypes
examined
χ2
p
RR
95%CI
OR
95%C
I
Neuropathy stage
II
Control group
n
%
n
%
S
8
9,1
27
15,0
1,8
0,20
0,6
0,17 - 2,1
0,6
0,25
- 1,29
Volume 03 Issue 11-2023
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03
ISSUE
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(2023:
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184
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P
80
90,9
153
85,0
1,8
0,20
1,7
1,11 - 2,46
1,8
0,77
- 4,03
S/P
8
18,2
19
21,1
0,2
0,70
0,9
0,25 - 3,01
0,8
0,33
- 2,08
P/P
36
81,8
67
74,4
0,9
0,40
1,1
0,31 - 3,95
1,5
0,63
- 3,79
Alleles
и
Genotypes
Number of alleles and genotypes
examined
χ2
p
RR
95%CI
OR
95%C
I
Neuropathy
grade III
Control group
n
%
n
%
S
6
10,7
27
15,0
0,7
0,50
0,7
0,16 - 3,18
0,7
0,27
- 1,73
P
50
89,3
153
85,0
0,7
0,50
1,4
0,99 - 1,99
1,5
0,58
- 3,75
S/P
6
21,4
19
21,1
0,0
0,98
1,0
0,22 - 4,75
1,0
0,36
- 2,87
P/P
22
78,6
67
74,4
0,2
0,70
1,1
0,22 - 5,06
1,3
0,45
- 3,48
Alleles
и
Genotypes
Number of alleles and genotypes
examined
χ2
p
RR
95%CI
OR
95%C
I
Neuropathy stage
I
Neuropathy stage
II
n
%
n
%
S
12
27,3
8
9,1
7,5
0,01
3,0
1,21 - 7,42
3,8
1,46
- 9,63
P
32
72,7
80
90,9
7,5
0,01
0,3
0,11 - 0,98
0,3
0,1 -
0,68
S/P
6
27,3
8
18,2
0,7
0,40
1,5
0,36 - 6,26
1,7
0,51
- 5,63
P/P
13
59,1
36
81,8
4,0
0,05
0,7
0,2 - 2,56
0,3
0,1 -
0,98
Volume 03 Issue 11-2023
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International Journal of Medical Sciences And Clinical Research
(ISSN
–
2771-2265)
VOLUME
03
ISSUE
11
P
AGES
:
38-52
SJIF
I
MPACT
FACTOR
(2021:
5.
694
)
(2022:
5.
893
)
(2023:
6.
184
)
OCLC
–
1121105677
Publisher:
Oscar Publishing Services
Servi
Alleles
и
Genotypes
Number of alleles and genotypes
examined
χ2
p
RR
95%CI
OR
95%C
I
Neuropathy stage
I
Neuropathy
grade III
n
%
n
%
S
12
27,3
6
10,7
4,6
0,05
2,5
1,11 - 5,84
3,1
1,1 -
8,88
P
32
72,7
50
89,3
4,6
0,05
0,4
0,1 - 1,48
0,3
0,11
- 0,91
S/P
6
27,3
6
21,4
0,2
0,70
1,3
0,34 - 4,8
1,4
0,37
- 5,04
P/P
13
59,1
22
78,6
2,2
0,20
0,8
0,23 - 2,42
0,4
0,12
- 1,34
Alleles
и
Genotypes
Number of alleles and genotypes
examined
χ2
p
RR
95%CI
OR
95%C
I
Neuropathy stage
II
Neuropathy
grade III
n
%
n
%
S
8
9,1
6
10,7
0,1
0,80
0,8
0,34 - 2,15
0,8
0,27
- 2,54
P
80
90,9
50
89,3
0,1
0,80
1,2
0,33 - 4,15
1,2
0,39
- 3,66
S/P
8
18,2
6
21,4
0,1
0,80
0,8
0,32 - 2,24
0,8
0,25
- 2,66
P/P
36
81,8
22
78,6
0,1
0,80
1,0
0,39 - 2,75
1,2
0,38
- 4,01
Table 2. Differences in the frequency of allelic and genotypic variants of the Ser249Pro polymorphism in the TLR6
gene in patient groups
Mutations in TLR genes are believed to act as a
prognostic marker for tumor progression. A SNP in a
DNA sequence is a single nucleotide substitution.
Almost all typical SNPs have only two alleles. SNPs are
found in the coding sequences of genes, noncoding
regions of genes, or intergenic regions. SNPs in the
Volume 03 Issue 11-2023
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:
38-52
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(2021:
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(2023:
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coding sequence are synonymous without changing
the amino acid sequence of the protein or
nonsynonymous, resulting in a different polypeptide.
SNPs in noncoding regions are reflected in changes in
gene splicing, binding of transcription factors, or in the
sequence of noncoding RNA. It has been shown that
SNPs in TLR genes lead to changes in a person's
susceptibility to infectious or inflammatory diseases
due to the inability to respond to the corresponding
ligands.
Factor
Groups
SE
SP
AUC
OR
95%CI
p
S
Main group // Control
group
0,14
0,85
0,5
0,91
0,51 - 1,62
0,51
Neuropathy stage I //
Control group
0,27
0,85
0,56
2,13
0,99 - 4,6
0,17
Neuropathy stage II //
Control group
0,09
0,85
0,47
0,57
0,25 - 1,29
0,34
Neuropathy grade III //
Control group
0,11
0,85
0,48
0,68
0,27 - 1,73
0,25
Neuropathy stage I //
Neuropathy stage II
0,27
0,91
0,59
3,75
1,46 - 9,63
0,29
Neuropathy stage I //
Neuropathy grade III
0,27
0,89
0,58
3,13
1,1 - 8,9
0,39
Neuropathy stage II //
Neuropathy grade III
0,09
0,89
0,49
0,83
0,27 - 2,59
0,62
Factor
Groups
SE
SP
AUC
OR
95%CI
p
P
Main group // Control
group
0,15
0,86
0,51
1,1
0,61 - 1,97
0,49
Neuropathy stage I //
Control group
0,15
0,73
0,44
0,47
0,22 - 1,01
0,83
Neuropathy stage II //
Control group
0,15
0,91
0,53
1,76
0,77 - 4
0,66
Volume 03 Issue 11-2023
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ISSUE
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P
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:
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SJIF
I
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FACTOR
(2021:
5.
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(2022:
5.
893
)
(2023:
6.
184
)
OCLC
–
1121105677
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Neuropathy grade III //
Control group
0,15
0,89
0,52
1,47
0,58 - 3,74
0,75
Neuropathy stage I //
Neuropathy stage II
0,09
0,73
0,41
0,27
0,11 - 0,69
0,71
Neuropathy stage I //
Neuropathy grade III
0,11
0,73
0,42
0,32
0,11 - 0,91
0,61
Neuropathy stage II //
Neuropathy grade III
0,11
0,91
0,51
1,2
0,39 - 3,66
0,38
Factor
Groups
SE
SP
AUC
OR
95%CI
p
S/S
Main group // Control
group
0,03
0,96
0,5
0,71
0,16 - 3,22
0,51
Neuropathy stage I //
Control group
0,14
0,96
0,55
3,39
0,76 - 15,17
0,18
Factor
Groups
SE
SP
AUC
OR
95%CI
p
S/P
Main group // Control
group
0,21
0,79
0,5
1,01
0,5 - 2,06
0,51
Neuropathy stage I //
Control group
0,27
0,79
0,53
1,4
0,49 - 4,04
0,18
Neuropathy stage II //
Control group
0,18
0,79
0,49
0,83
0,33 - 2,08
0,34
Neuropathy grade III //
Control group
0,21
0,79
0,5
1,02
0,35 - 3,01
0,24
Neuropathy stage I //
Neuropathy stage II
0,27
0,82
0,55
1,69
0,51 - 5,65
0,31
Neuropathy stage I //
Neuropathy grade III
0,27
0,79
0,53
1,38
0,37 - 5,14
0,42
Volume 03 Issue 11-2023
47
International Journal of Medical Sciences And Clinical Research
(ISSN
–
2771-2265)
VOLUME
03
ISSUE
11
P
AGES
:
38-52
SJIF
I
MPACT
FACTOR
(2021:
5.
694
)
(2022:
5.
893
)
(2023:
6.
184
)
OCLC
–
1121105677
Publisher:
Oscar Publishing Services
Servi
Neuropathy stage II //
Neuropathy grade III
0,18
0,79
0,49
0,81
0,24 - 2,74
0,62
Factor
Groups
SE
SP
AUC
OR
95%CI
p
P/P
Main group // Control
group
0,76
0,26
0,51
1,06
0,54 - 2,07
0,5
Neuropathy stage I //
Control group
0,59
0,26
0,43
0,5
0,19 - 1,29
0,28
Neuropathy stage II //
Control group
0,82
0,26
0,54
1,54
0,63 - 3,75
0,26
Neuropathy grade III //
Control group
0,79
0,26
0,53
1,26
0,45 - 3,5
0,21
Neuropathy stage I //
Neuropathy stage II
0,59
0,18
0,39
0,32
0,1 - 0,98
0,53
Neuropathy stage I //
Neuropathy grade III
0,1
0,21
0,16
0,03
0 - 0,18
0,6
Neuropathy stage II //
Neuropathy grade III
0,82
0,21
0,52
1,23
0,37 - 4,07
0,57
Table 3. Prognostic effectiveness of the studied genetic markers (Ser249Pro polymorphism in the TLR6 gene)
We carried out a statistical analysis of the expected and
observed frequencies of the distribution of genotypes
of the locus for RHV (Ser249Pro polymorphism in the
TLR6 gene) and the data are shown in Table 4.
Main group
Alleles
Allele frequency
S
0,14
P
0,86
Genotypes
Genotype frequency
χ2
p
df
observable
expected
S/S
0,03
0,02
0,8
Volume 03 Issue 11-2023
48
International Journal of Medical Sciences And Clinical Research
(ISSN
–
2771-2265)
VOLUME
03
ISSUE
11
P
AGES
:
38-52
SJIF
I
MPACT
FACTOR
(2021:
5.
694
)
(2022:
5.
893
)
(2023:
6.
184
)
OCLC
–
1121105677
Publisher:
Oscar Publishing Services
Servi
S/P
0,21
0,24
0,26
P/P
0,76
0,74
0,02
Total
1
1
1,08
0,284
1
Control group
Alleles
Allele frequency
S
0,15
P
0,85
Genotypes
Genotype frequency
χ2
p
df
observable
expected
S/S
0,04
0,02
1,93
S/P
0,21
0,26
0,68
P/P
0,74
0,72
0,06
Total
1
1
2,67
0,099
1
Groups
Ho
He
D*
Main group
0,21
0,24
-0,11
Control group
0,21
0,26
-0,17
Note: D = (Ho - He)/He
Expected and observed frequencies of distribution of genotypes of the locus for RHV
(Ser249Pro polymorphism in the TLR6 gene)
Neuropathy stage I
Alleles
Allele frequency
S
0,27
P
0,73
Genotypes
Genotype frequency
χ2
p
df
observable
expected
Volume 03 Issue 11-2023
49
International Journal of Medical Sciences And Clinical Research
(ISSN
–
2771-2265)
VOLUME
03
ISSUE
11
P
AGES
:
38-52
SJIF
I
MPACT
FACTOR
(2021:
5.
694
)
(2022:
5.
893
)
(2023:
6.
184
)
OCLC
–
1121105677
Publisher:
Oscar Publishing Services
Servi
S/S
0,14
0,07
1,14
S/P
0,27
0,4
0,85
P/P
0,59
0,53
0,16
Total
1
1
2,15
0,145
1
Control group
Alleles
Allele frequency
S
0,15
P
0,85
Genotypes
Genotype frequency
χ2
p
df
observable
expected
S/S
0,04
0,02
1,93
S/P
0,21
0,26
0,68
P/P
0,74
0,72
0,06
Total
1
1
2,67
0,099
1
Groups
Ho
He
D*
Neuropathy stage I
0,27
0,4
-0,31
Control group
0,21
0,26
-0,17
Note: D = (Ho - He)/He
Expected and observed frequencies of distribution of genotypes of the locus for RHV
(Ser249Pro polymorphism in the TLR6 gene)
Neuropathy stage II
Alleles
Allele frequency
S
0,09
P
0,91
Genotypes
Genotype frequency
χ2
p
Volume 03 Issue 11-2023
50
International Journal of Medical Sciences And Clinical Research
(ISSN
–
2771-2265)
VOLUME
03
ISSUE
11
P
AGES
:
38-52
SJIF
I
MPACT
FACTOR
(2021:
5.
694
)
(2022:
5.
893
)
(2023:
6.
184
)
OCLC
–
1121105677
Publisher:
Oscar Publishing Services
Servi
observable
expected
df
S/S
0
0,01
0,36
S/P
0,18
0,17
0,07
P/P
0,82
0,83
0
Total
1
1
0,44
0,483
1
Control group
Alleles
Allele frequency
S
0,15
P
0,85
Genotypes
Genotype frequency
χ2
p
df
observable
expected
S/S
0,04
0,02
1,93
S/P
0,21
0,26
0,68
P/P
0,74
0,72
0,06
Total
1
1
2,67
0,099
1
Groups
Ho
He
D*
Neuropathy stage II
0,18
0,17
0,1
Control group
0,21
0,26
-0,17
Note:D = (Ho - He)/He
Expected and observed frequencies of distribution of genotypes of the locus for RHV
(Ser249Pro polymorphism in the TLR6 gene)
Neuropathy grade III
Alleles
Allele frequency
S
0,11
Volume 03 Issue 11-2023
51
International Journal of Medical Sciences And Clinical Research
(ISSN
–
2771-2265)
VOLUME
03
ISSUE
11
P
AGES
:
38-52
SJIF
I
MPACT
FACTOR
(2021:
5.
694
)
(2022:
5.
893
)
(2023:
6.
184
)
OCLC
–
1121105677
Publisher:
Oscar Publishing Services
Servi
P
0,89
Genotypes
Genotype frequency
χ2
p
df
observable
expected
S/S
0
0,01
0,32
S/P
0,21
0,19
0,08
P/P
0,79
0,8
0
Total
1
1
0,4
0,502
1
Control group
Alleles
Allele frequency
S
0,15
P
0,85
Genotypes
Genotype frequency
χ2
p
df
observable
expected
S/S
0,04
0,02
1,93
S/P
0,21
0,26
0,68
P/P
0,74
0,72
0,06
Total
1
1
2,67
0,099
1
Groups
Ho
He
D*
Neuropathy grade III
0,21
0,19
0,12
Control group
0,21
0,26
-0,17
Note: D = (Ho - He)/He
Таблица 4. Expected and observed frequen
cies of distribution of genotypes of the locus for RHV (Ser249Pro
polymorphism in the TLR6 gene)
Thus, the TLR6 gene has a significant impact on the
development
and
progression
of
myeloma
complications. Its role is associated with the regulation
of the immune response and the interaction of tumor
cells with the microenvironment. Mutations and
polymorphisms of the TLR6 gene may be associated
with an increased risk of developing more aggressive
variants of myeloma. Further research in this area will
Volume 03 Issue 11-2023
52
International Journal of Medical Sciences And Clinical Research
(ISSN
–
2771-2265)
VOLUME
03
ISSUE
11
P
AGES
:
38-52
SJIF
I
MPACT
FACTOR
(2021:
5.
694
)
(2022:
5.
893
)
(2023:
6.
184
)
OCLC
–
1121105677
Publisher:
Oscar Publishing Services
Servi
allow us to better understand the molecular
mechanisms associated with the TLR6 gene and
develop new therapeutic approaches to prevent and
treat complications of myeloma.
REFERENCES
1.
Bohnert V, Schäfer C, Müller-Tidow C, et al. Toll-like
receptors in normal and malignant hematopoiesis.
Curr
Pharm
Des.
2006;12(32):4219-4232.
doi:10.2174/138161206779010392
2.
Vacca A, Ribatti D, Presta M, et al. Bone marrow
neovascularization,
plasma
cell
angiogenic
potential,
and
matrix
metalloproteinase-2
secretion parallel progression of human multiple
myeloma. Blood. 1999;93(9):3064-3073.
3.
Kawai T, Akira S. The role of pattern-recognition
receptors in innate immunity: update on Toll-like
receptors. Nat Immunol. 2010;11(5):373-384.
doi:10.1038/ni.1863
4.
Vacca A, Ria R, Reale A, et al. TLR gene expression
profile in human multiple myeloma cells: down-
regulation of TLR3 expression. Cancer Immunol
Immunother.
2006;55(7):910-920.
doi:10.1007/s00262-005-0079-1
5.
Botta C, Gulla A, Correale P, Tagliaferri P, Tassone
P. Myeloma cells suppress osteoblasts through
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