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17
Section 1. Clinical medicine
DOI: http://dx.doi.org/10.20534/ELBLS-16-4-14-17
Gulyamova Gulchechekhra Shuhratovna, Mavlyanova Shahnoza Zakirovna, Boboev Abdukadir Tuhtabaevich The Republican Specialized Scientific-practical Medical Center of Dermatology and Venerology of the Ministry of Health of the Republic of Uzbekistan Scientific Research Institute of Hematology and Blood Transfusion of Ministry of Health of the Republic of Uzbekistan E-mail: gulyamova.1971@mail.ru
Clarifying the function of xenobiotic biotransforming of enzymes throughout the gradual development of atopic dermatitis
Abstract: The given article covers the genotypic options of polymorphic genes of xenobiotic biotransformation enzymes by phase II GSTM1 (lp 13.3), GSTT1 (22q 11.2) excretion in the development of atopic dermatitis among patients throughout the population of Uzbekistan. There is a noticeably frequent increase in carriers of deletion of polymorphism genes GSTM 10/0/GSTT 0/0 comparably to those healthy donors on condition. Thus, it is obvious to assume that those are likely to be susceptible to atopic dermatitis with genetic predisposition.
Keywords: Atopic dermatitis, genetics, Polymorphism of GSTM1, GSTT1.
Despite the study conducted on stigmatization and cieties. The meta-analysis results reveal the fact that there the early detection of the disease, laboratory tests still re- are interethnic distinctions about the spread of atopic main insufficient responding to the complexity ofpatho- dermatitis. Thus, it was reported that there is an associa-genesis of atopic dermatitis. The source analysis reveals tion responding to the atopic dermatitis marker among the fact that the causes of the allergic diseases, especially several populates yet other populates hadn't. atopic dermatitis development are regarded by the envi- The recent analysis results enlighten the fact that
ronmental, geographic conditions as well as ethnic spe- there are still controversial issues on connection of cifics of the population, individually to those susceptible polymorphism of GSTT 1, GSTM 1 genes; therefore, genes throughout the society [1; 2; 3; 4; 5; 6]. it is hardly impossible to determine the significance of
According to the results of foreign and national stud- the above genes in the development of atopic dermati-ies, the development of multifactorial diseases, particu- tis. There are still insufficient molecular-genetic stud-larly allergic diseases just as rhinitis, bronchial asthma, ies dedicated to the specific atopic dermatitis diseases atopic dermatitis are mainly associated with several amongst Uzbekistan population, moreover researches polymorphic variant of genes as RANTES, TNF-alpha, on the importance of polymorphism of GSTT 1, GSTM GDTT1, GDTM 1, and CTLA 4 [2; 3; 7; 8; 9]. 1 genes in the atopic dermatitis formation have never
Series of studies were dedicated to the analysis of been conducted in Uzbekistan. polymorphism genes of xenobiotic biotransformation Research targeted to: Evaluate the pathogenic
of enzymes by phase II as GSTT 1, GSTM 1 and their distinction of genotypic variants of xenobiotic bio-relationship to atopic dermatitis throughout various so- transformation of enzyme genes GSTM 1 (1p 13.3),
Clarifying the function of xenobiotic biotransforming of enzymes throughout the gradual development of atopic dermatitis
GSTT 1 (22q 11.2) in the gradual development atopic dermatitis.
Covered sources and experimentation overview:
The atopic dermatitis patients, the DNA samples of sick and healthy donors, glutathione transferases genes of GSTM 1 (lp 13.3), GSTT 1 (22q 11.2) were taken as the object of investigation. The 79 patients aged from 4 up to 50followed in the Republican Specialized Scientific-practical Medical Center of Dermatology and Venerol-ogy of the Ministry of Health of the Republic of Uzbekistan were included and observed in the study. The total amount of patients was subdivided into 41 female and 38 male patients. All the above patients were clinically tested and their diagnosis was verified on the basis of laboratory tests. (SCORAD, dermatologic index identification test). All the patients were examined, forwarded and treated in Dermatology unit of the Medical center. The molecular genetic examination of genetic resources and bio-materials (DNA) were examined in the cellular technology and molecular medicine department of the Scientific Research Institute of Hematology and Blood Transfusion.
As a comparative population analysis elements presented by DNA samples of healthy donors (without any reference to atopic dermatitis) were tested and commissioned by this unit of Hematology and Blood Transfusion Center. The DNA samples were extracted from peripheral blood lymphocytes according to enhanced approach. The concentration and the purity level of DNA patterns were rated by measuring the optical density of DNA contained solutions by means of260 and 280 NM waves against TE using the IR-spectrophotometer Nano-Drop 200 (Produced in the USA).
Evaluating the polymorphic genotype variants of GSTT 1, GSTM 1was carried out through PCR analysis with the help of programmable PCR-thermocyclers CG-1-96 "Corbett Research" (Australia) and 2720 "Applied biosystems" (USA) using the rapid test systems of "MedLab" (Russia) referring to manufacturer's directions.
Statistical processing of the results: The deviation of polymorphic genotypes distribution assessment (extracted from DNA) by the canonical distribution of Hardy Veinberg was conducted using the selected computer program of genetic data analysis "Gene Pop" (Genetics of Population). The genotypes (f) and allele ofpolymor-phic variants were calculated by the given formula:
F=n/2N u f=n/N, where n-is the abundance of the allele or genotype, N-the data extraction
The allele abundance analysis was calculated by p= (2N\+N2)/2N, q= (2N3+N2)/2N, where p=as the allele regularity of A, q as the allele regularity of a, N as the general data extraction of the N=N|+N2+N3, pointing that N|, N2, N3-is respectively the amount of individuals with AA, Aa and aa genotypes a set of statistics calculation program "OpenEpi 2009, Version 2.3" was used for totaling of OR-odds ratio with 95%of confidence interval, X2 and for p-figures.
The relative dissemblance of the expected performance of heterozygosity from the observed one was calculated by
D= (h. - h ) h
v obs exp/ exp
where h , and h are pointing the observed and expect-
obs exp
ed heterozygosity.
The prognostic efficiency (AUC-classifier) of the genetic markers were defined by AUC= (Se+Sp)\2 standard formula where Se and Sp where is the Sensitivity and Specificity of the genetic marker. In the case that AUCA 0,5, is index whereas marker is a random classifier; AUC=0,5-0,6 is unsatisfactory or bad; AUC=0,6-0,7 — average; AUC= 0,7-0,8 satisfactory; AUCA0,8 as the excellent classifier (Hosmer D. W., Lemeshow S. et al., 2000).
The results review and commentary: No distinctive features were found among the expiremented groups and subgroups (PA0,05) during the process of investigation of GSTM 10/0.
During the identification of deletion of polymorphism of GSTM1 0/0 there was a noticeable increase which was found amongst those experimented with an adverse allele (44.3% in comparison to 23,7 within the controlled groups ofpeople; X2=7,5; p=0,006; OR=2,6; 95%CI 1.294, 5.04).
The frequency distribution of combined genotypes of deletion ofpolymorphism genes GSTM1 and GSTT1 throughout the observed groups
As it is known, the study of genotype frequency of GSTM 1 and GSTT1 particularly for each of the enzymes doesn't allow us the whole vision on the formation ofxenobiotics conjugation phenotype with glutathione in vivo (i. e. The comprehensive nature of the entire system of antioxidant organism defense).
Therefore, it was obvious for us to assess the frequency distribution of combined genotypes in prior throughout the groups of atopic dermatitis patients and healthy donors. We priorly examined four gaplotypes; (see the Table 1 for further information).
As can be noted in Table 1, those individuals with functionally defective genotypes.
Table 1.
Observed group The distribution frequency of genotypes
GSTM 0/0 + GSTT0/0 GSTM 0/0 + GSTT «+» GSTT 0/0+ GSTM «+» GSTM «+» GSTT «+»
n % n % n % n %
The primary group n*= 79 7 8.9 17 21.5 28 35.4 27 34.2
Mild forms n*= 31 3 9.7 6 19.3 10 32.3 12 38.7
Average forms n*=26 2 7.7 6 23.1 8 30.8 10 38.5
Severe forms n*=22 2 9.1 5 22.7 10 45.4 5 22.7
Control n*=80 3 3.75 31 38.7 15 18,7 31 38.8
* n amount of observed patients
GSTM 10/0+GSTT 10/0 among atopic dermatitis patients was more frequent through the controlled group as compared: 8,95 and 3,7%. In doing so, it is noticeable to claim that atopic dermatitis development risk is exceptionally higher with GSTT 1 0/0 +GSTM 1 0/0.
However, the given outcome hasn't yet reached the level of statistical significance throughout the observation of combined genotypes of GSTT1 and GSTM1 genes in atopic dermatitis depending on diseases' subtype. It was revealed that GSTT 10/0+ GSTM 10/0 combinations exceeded almost amongst all observed subgroups frequently than controlled group on the whole.
Based on calculated odds ratio it is claimed that GSTM 0/0+GSTT 0/0 bearing indicates to AD development risk of mild forms increases almost 2.7 times higher as well as patients with severe form of AD are relatively more prevalent to GSTT1 0\0+GSTM1 0/0 genotype. (X2=1,0: P=0,3; OR=2,6; 95% CI 0,4014, 16.41). However these results weren't approved statistically, i. e. conjugation phenotype together combined of deletion genotypes of glutathione-S-transpherase, wasn't associated to severity and development of the disease based on investigation. It is most likely to notice that polymorphism deletion genes GSTM 10/0 GSTT 0/0 are less frequent throughout the local population.
The frequent abundance of remained genotypes of GSTM 1 and GSTT1 out of the general group of patients do not differ from the given controlled group. (p 60,05), i. e., probably refers to atopia. The comparative test of the frequency distribution ofstudied genotypes in AD patients with its different forms joined with experimentally healthy patients hasn't identified any differences among patients. (pA0,05). The analysis of illness development progress has also revealed the statistically unreliable outcome of the deviation from normal distribution.
The statistically unreliable facts ofthode comparisons, probably referred to low frequency of deletion of polymorphism combination of GSTM 10/0 GSTT 0\0 through our population.
Outcome: Therefore we found the statistical difference between «zero» genotypes of GSTT1 and GSTM1 genes amongst AD patients and controlled group. Though significant (not statistically approved) frequency of deletion of polymorphism genes GSTM 10\0 GSTT 0\0 among the group of AD patients was identified parallel to healthy donors, i. e., it would be likely to assume about of the existence of genetic component to atopic dermatitis.. Statistical unreliable facts of those experimented comparisons probably refers to low frequency deletion polymorphism of GSTM 10\0 and GSTT 0\0 combination throughout our population.
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"Epigenorm forte" —
Russian parapharmaceuticals for the prevention and complex treatment of oncological diseases
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DOI: http://dx.doi.org/10.20534/ELBLS-16-4-17-21
Kornilov Sergey Ivanovich, "Doctor Kornilov Ltd", Barnaul E-mail: dokskor@list.ru Gaidul Konstantin Valentinovich, Ph. D., Professor, "Institute of fundamental and clinical immunology", Novosibirsk
E-mail: kgaidul@mail.ru
"Epigenorm forte" — Russian parapharmaceuticals for the prevention and complex treatment of oncological diseases
Abstract: This article presents the results of experimental studies of a new parapharmaceutics "Epigenorm forte", reflecting its antitumor, antimetastatic and anti-toxic properties.
Keywords: "Epigenorm forte", adenocarcinoma Lewis, Ehrlich's adenocarcinoma, melanoma B-16, doxorubicin, cyclophosphamide, 5-fluorouracil.
Корнилов Сергей Иванович, Компания «Доктор Корнилов», г. Барнаул E-mail: dokskor@list.ru Гайдуль Константин Валентинович, д. м.н., профессор, «<НИИ фундаментальной и клинической иммунологии», г. Новосибирск E-mail: kgaidul@mail.ru
«Эпигенорм форте» — российский парафармацевтик для профилактики и комплексного лечения онкологических заболеваний
Аннотация: В данной статье представлены результаты экспериментальных исследований нового парафармацевтика «Эпигенорм форте», отражающие его противоопухолевые, антиметастатические и антитоксические свойства.
