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Genetic polymorphism of cytokines in patients with keloids
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Sabirov Ulugbek Yusuphanovich, Director of Republican Specialized Science Practical Medical Center of Dermatology & Venereology, Republic of Uzbekistan
Toirov Bobur Akbarovich, Junior researcher Azimova Fatima Vakhidovna, Senior staff scientist E-mail: [email protected]
Genetic polymorphism of cytokines in patients with keloids
Abstract: An ongoing study examined the DNA of an interleukin-6 (IL-6) and interleukin-1 (IL-1) in patients with keloids. The results of the research of gene polymorphisms S3953T gene IL-1B and G-174C gene IL-6 is a marker of increased risk of developing the disease, in particular, is clearly expressed with homozygous genotype polymorphism G-174C IL-6 gene. Distribution of allele frequencies of genes IL-1^ and IL-6, consistent with the law of the expected Hardy-Weinberg equilibrium (P > 0.05). Keywords: Keloids, homozygous genotype, gene polymorphism.
nuclei of lymphocytes was carried out according to the procedure described in the manual Sambrook et al., with some modifications.
Statistical processing of the results of research carried out by the method of variation statistics using Microsoft Office Ex-cel-2003 program.
Results of the study
In order to determine the frequency distribution of genetic variants of the gene mutation G-174C IL-6 gene, we performed a molecular analysis of DNA among relatively healthy donors and patients with keloids [3]. In 25 patients and 20 apparently healthy donors, G allele of IL-6 gene (G-174C) was found 85 % and 96 % of cases, respectively (Table 1). CC allele gene IL-6 (G-174C) were observed respectively in 15 % and 4 % of cases. In assessing the characteristics of the distribution of genotypes and allelic variants of the IL-6 polymorphism (G-174C) in patients with keloid scars it revealed that the differences in the frequency of alleles and genotypes between patients examined men and women were invalid character. A comparative analysis of the
Currently, one of the urgent problems of dermatology are skin diseases associated with impaired collagen synthesis (keloid), and manifesting the development ofvarious degenerative lesions of the skin, reducing the quality of life [1; 2].
Purpose of the study
Carrying out the molecular genetic studies of genotype polymorphism S3953T gene IL-1p and G-174C IL- 6 gene in patients with keloids.
Materials and methods
An ongoing study examined the DNA of an interleukin-6 (IL- 6) and interleukin-1 (IL-1) in 25 patients with keloids and 20 apparently healthy donors (control group). All the subjects resided in the territory of Uzbekistan and had no family ties between them. Comorbidities in patients with keloids was introduced diseases of the gastrointestinal tract (70 %), iron-deficiency anemia (30 %), diffuse goiter of varying degrees (23 %).
In the first stage extraction was carried out from genomic DNA of peripheral blood lymphocytes. Isolation of DNA from
Section 5. Medical science
genotype frequencies of the polymorphism of IL-6 (G-174C) the and C/C (5 %) only among the patients. Heterozygous genotype most significant in the examined groups of men and women were G/C IL-6 gene (G-174C) was observed in the group of patients homozygous genotype G/G (75 % ofpatients and 92 % of normal) (20 %) and in the control group (8 %).
Table 1. - The frequency distribution of alleles and genotypes of polymorphism G-174C IL- 6 gene
The frequency of alleles The frequency distribution of genotypes
Group N G C G/G G/C C/C
n % n % n % n % n %
Core group 20 34 85.0 6 15.0 15 75.0 4 20.0 1 5.0
Control group 25 48 96.0 2 4.0 23 92.0 2 8.0 0 0.0
Alleles: X2 = 3.3; p = 0.06; OR=4.235; 95 % CI 0.8058, 22.26.
Genotypes: G/G: x2 = 2.2; P = 0.1; OR = 0.3; 95 %CI 0.65, 22.3.
G/C + CC: X 2 = 2.4; P = 0.1; OR = 3.833; 95 % CI 0.6569, 22.37.
With regard to the distribution of features allelic variants and polymorphism genotypes S3953T gene IL-1p allele G gene among patients and the control group it was found 87.5 % and 94 % of cases, respectively (Table 2). T allele of the gene IL-1^ (S3953T) was found in 12.5 %, respectively (for patients) and 6 % (including the control group) cases. In assessing the characteristics of the distribution of genotypes and allelic variants of the Table 2. - The frequency distribution of allele
polymorphism IL-1^ (S3953T) in patients with keloid scars it revealed that the differences in the frequency of alleles and genotypes between patients examined men and women were invalid character. A comparative analysis of the genotype frequencies of the polymorphism of IL-6 (G-174C) the most significant in the examined groups of men and women were homozygous genotype G/G (75 % of patients and 92 % of normal) and C/C (5 %) only among the patients. Heterozygous genotype G/C IL-6 gene (G-174C) was observed in the group of patients (20 %) and in the control group (8 %). and genotype polymorphism S3953T gene IL-ip
Group N The frequency of alleles The frequency distribution of genotypes
C T C/C C/T T/T
n % n % n % n % n %
Core group 20 35 87.5 5 12.5 15 75.0 5 25.0 0 0.0
Control group 25 47 94.0 3 6.0 22 88.0 3 12.0 0 0
Total group and control:
Alleles: x2 = 1.3; P = 0.3; OR=2.24; 95 % CI 0.5011, 9.997.
Genotypes: C/C: x2 = 1.2; P = 0.2; OR = 0.4; 95 % CI 0.50, 11.8.
C/T: X2 = 1.3; P = 0.3; OR=2.4; 95 % CI 0.5062, 11.8.
In order to determine the effectiveness of a genetic marker were calculated sensitivity (SE), specificity (SP) and the index of AUC (areaundercurve). Prognostic value was determined as follows: if the index AUC < 0.5, the marker — the occasional qualifier; 0.5 < AUC < 0.6 — bad, 0.6 < AUC < 0.7 — average; 0.7 < AUC < 0.8 — good; AUC > 0.8 — a great qualifier. The results of calculation of the efficiency of the studied loci S3953T Table 3. - Sensitivity (SE), specificity (S
gene IL-1p and G-174C gene IL-6 as an independent marker of collagen remodeling identified statistically insignificant. However, one could note the relatively high level of sensitivity with the index locus rs1800795 SE = 0.92 (95 %, CI: 0.80 -22.26), with SP = 0.25 (Table 3).
By using the Fisher exact test was to check the distribution of polymorphic loci examined for compliance with the Hardy-Wein-berg equilibrium.
Observed races — bution (tab. 4, 5, 6, 7) heterozygous genotypes both loci correspond Augy, Aisne — giving law to the Hardy-Weinberg equilibrium (P > 0.05). component and AUC (area under curve)
Polymorphisms SP SE AUC OR (95 %CI) P
rs1143634 0.25 0.88 0.56 2.2 (0.5011, 9.997) 0.3
rs1800795 0.25 0.92 0.58 4.2 (0.80 -22.26) 0.06
Table 4. - The difference between the expected and observed frequencies of heterozygosity polymorphism among patients S3953T gene IL-ip
Genotypes genotype frequency x2 P
expected observed
C/C 76.56 75.00 0.006 0.5229
C/T 21.88 25.00 0.089
T/T 1.56 0.00 0.313
Total 100.00 100.00 0.408
Table 5. - The difference between the expected and observed frequencies of heterozygosity polymorphism among IL-1B gene controls S3953T
Genotypes genotype frequency x2 P
expected observed
C/C 88.36 88.00 0.000 0.7496
C/T 11.28 12.00 0.011
T/T 0.36 0.00 0.090
Total 100.00 100.00 0.102
Table 6. - The difference between the expected and observed frequencies of heterozygosity polymorphism among patients with G-174C IL-6 gene
Genotypes genotype frequency x2 P
expected observed
G/G 72.25 75.00 0.021 0.3348
G/C 25.50 20.00 0.237
C/C 2.25 5.00 0.672
Total 100.00 100.00 0.930
Table 7. - The difference between the expected and observed heterozygosity polymorphism frequencies among the control group G-174C IL-6 gene
Genotypes genotype frequency x2 P
expected observed
G/G 92.16 92.00 0.000 0.8350
G/A 7.68 8.00 0.003
A/A 0.16 0.00 0.040
Total 100.00 100.00 0.043
The modern principles of surgical treatment in non-organ retroperitoneal tumors
The analysis of DNA polymorphisms distribution of two genes involved in the regulation of the functional activity of cytokines found:
- Frequency distribution of alleles IL-1p and IL- 6, consistent with the law of the expected Hardy-Weinberg equilibrium (P > 0.05);
- Among the examined patients with keloid scars in the presence of genotype-national function allele and genotype polymorphism S3953T gene IL-1p detected in 12.5 % and 25.0 %, respectively, compared with 6.0 % and 12.0 % in the control group, and is associated with a than 2-fold increased risk of diseases associated with collagen remodeling. However, these differences were not significant article cally (x2 = 1.3; P = 0.3; OR=2.4; 95 % CI 0.5062, 11.8); The genotype homozygous for the allele C/C, on the contrary, was protective against such states (x2 = 1.2; P = 0.2; OR = 0.4; 95 % CI 0.50, 8.11). However, its frequency was statistically insig-nificant-telno lower in the group of patients with keloids (75.0 %) than in controls (88.0 %). In the studied group of people with homozygous genotype were found;
- incidence functionally inactive alleles and genotypes of G-174C polymorphism in the gene IL-6 in patients with keloids significantly higher than in control group con (6 % and 25.0 % versus 4.0 % and 8.0 %, respectively).
Heterozygous for the presence of allele G/C in the group of patients with keloids met insignificantly more frequently than in the control group (20.0 % vs. 8.0 %, P > 0.05). A combination of two rare allelic variants not significantly more common also in the group of patients (25.0 %) compared with the control group (2.0 %). According to remodeling odds ratio, risk of collagen remodeling in patients in the presence of genotype — G/C + C/C is increased by more than 3.5 times (x2 = 2.4; P = 0.1; OR = 3.8; 95 % CI 0.6569, 22.37). Conclusion
The association between the polymorphic variants of genes IL-1^ second IL-6 and the development of pathological conditions involving remodeling call gene. According to preliminary results of polymorphisms of genes S3953T gene IL-1^ and G-174C IL-6 gene is a marker of increased risk of disease development, it is clearly expressed with homozygous genotype polymorphism G-174C IL-6 gene. The results reveal some aspects of the genetics of pathological process in keloid scars and indicate the advisability of continuing the first study of polymorphisms of genes involved in the pathogenesis of diseases involving the degeneration of collagen.
References:
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Ulmasov Firdavs Gayratovich, Djuraev Mirjalol Dehkonovich, Yusupbekov Abrorbek Ahmedjanovich, National research center of oncology of Uzbekistan E-mail: [email protected]
The modern principles of surgical treatment in non-organ retroperitoneal tumors
Abstract: The article provides a data of immediate and long term results of surgical treatment in 208 patients with locally spread nonorganic retroperitoneal tumors. Malignant tumors constituted 152 (71.3 %) while benign tumors 56 (26.9 %). Radical operations were performed to 64.8 % of patients, palliative — 26.7 % and in 8.3 % of cases operations were cytoreductive. From these, in 52.8 % of cases operations had combined character. General, Intra- and postoperative complications constituted 16.4 %, meanwhile postoperative lethal outcomes — 2.4 %. 5-year survival rate of patients with benign tumors reached 83.3 %, and malignant — 12.6 %. The same index after radical operation constituted 41,3 %, and after non radical — 9.6 %. Relapses within 5 years after surgery for a malignant tumor occurred in 73.7 %, and after a benign tumor — 26.3 % of patients.
Kaywords: retroperitoneal, non-organ, tumor, operation, radical, surgical, size, combined, anastomosis.
Relevance
Non-organ malignant retroperitoneal tumors according to WHO (2013) is 0.3-0.4 % in the structure of cancer pathology [4].
According National cancer research center (NCRC) of Uzbekistan recorded annually 80-86 cases of retroperitoneal tumors with non-organ origins representing 0.4 % of all cancer.
Statistical analysis of the last 5 years shows that more than 50 % of tumors are locally advanced character that required conducting combined operations [1; 2].
Due to the inaccessibility of the region and since these tumors often give no or non-specific symptoms until they have reached a substantial size, they are usually large at presentation. Sarcomas
comprise a third of retroperitoneal tumors, with two histological subtypes predominating, namely liposarcoma (70 %) and leiomyosarcoma (15 %). Other retroperitoneal neoplasms include primary lymphoproliferative tumors (Hodgkin's and non-Hodgkin lymphoma) and epithelial tumors (renal, adrenal, pancreas) or might represent metastatic disease from known or unknown primary sites (germ cell tumors, carcinomas, melanomas). Benign tumors can cause concern and are often an incidental finding during an investigation for unrelated symptoms [3].
They may be referred on suspicion ofbeing a sarcoma. The most common benign pathologies encountered in the retroperitoneum include benign neurogenic tumors (schwannomas, neurofibromas),
