Rs1800629 Polymorphism Research Articles

Stat4 rs7574865 polymorphism promotes the occurrence and progression of hepatocellular carcinoma via the Stat4/CYP2E1/FGL2 pathway

Although there are many studies on the relationship between genetic polymorphisms and the incidence of diseases, mechanisms are rarely known. We report the mechanism by which signal transducer and activator of transcription 4 (stat4) rs7574865 promotes the occurrence and progression of hepatocellular carcinoma (HCC). We found that the GG genotype at stat4 rs7574865 was a risk genotype, and STAT4 levels in serum and peritumoral tissue from HCC patients with the GG genotype were significantly higher than those found in TT or TG carriers. Furthermore, HCC patients with the GG genotype or elevated STAT4 levels had poor prognoses. In vitro experiments demonstrated that STAT4 silencing promoted apoptosis and inhibited the invasion and migration of HepG2 and L02 cells. Proteomic analysis of HCC peritumors identified 273 proteins related to STAT4, of which CYP2E1 activity and FGL2 content exhibited the highest positive correlation. The relationship between CYP2E1 and FGL2 was also confirmed in cyp2e1−/− mice and in CYP2E1 inhibitor-treated mice. In conclusion, this study elucidates the mechanism by which the stat4 rs7574865 polymorphism promotes the occurrence and progression of HCC via the Stat4/CYP2E1/FGL2 pathway.

Association of Genetic Variants in IL6 Gene (rs1800795) with the Concentration of Inflammatory Markers (IL-6, hs-CRP) and Superoxide Dismutase in the Blood of Patients with Acute Pancreatitis-Preliminary Findings.

In the course of acute pancreatitis, interleukin-6 plays an important role as a mediator in the inflammatory response. The course of inflammatory disease is associated with intensive oxidative stress, which may activate transcription factors leading to gene-expression changes. Isoenzymes of superoxide dismutase are involved in the defense against free radicals. This study aimed to evaluate changes in IL-6 concentration and the concentration/activity of superoxide dismutase isoenzymes (SOD1, SOD2, and SOD3) in the blood of patients with acute pancreatitis (AP) in terms of rs1800795 polymorphism in the IL6 gene. In the smoking AP patients group with the GC and GG genotypes, the plasma SOD1 concentration was significantly higher (p = 0.0146 and p = 0.0250, respectively) than in patients with CC genotype for SNP rs1800795 in the IL6 gene. An increase in SOD1 concentration in erythrocytes of AP patients with GC genotypes was also demonstrated compared to the individuals from the group with GG genotype (p = 0.0408). Furthermore, a positive correlation between IL-6 and SOD1 concentrations in the plasma of AP patients with GC genotype for SNP rs1800795 was shown. These results indicate that SOD1 may play a protective role against oxidative damage induced by inflammation in the group of AP patients with GC genotype.

Effect of vitamin D receptor gene polymorphism on lipid profile in Egyptian children with juvenile idiopathic arthritis

Aim of the workTo assess the effect of vitamin D receptor (VDR) polymorphism on lipid profile in patients with juvenile idiopathic arthritis (JIA) and study its relation to disease characteristics. Patients and methodsThe study included 55 JIA children and 55 matched controls. The lipid profile including cholesterol, high and low-density lipoprotein (HDL and LDL), and triglycerides was assessed. The single nucleotide polymorphism (SNP) VDR gene (rs2228570) polymorphism was assayed by real-time polymerase chain reaction (PCR) in patients and control. Results:55 JIA patients were 36 girls and 19 boys (F:M 1.9:1) and with a mean of age 8.4 ± 3.1 years (3–13 years) and disease duration 1.8 ± 1.4 years (2 months −8 years). Cholesterol, LDL, and triglycerides were significantly higher (175.4 ± 12.9 mg/dl vs 140.4 ± 7.3 mg/dl, 95.9 ± 9.3 mg/dl vs 71.4 ± 8.1 mg/dl, 95.4 ± 8.3 mg/dl vs 89.3 ± 9.1 mg/dl respectively) while the HDL was significantly lower (52.6 ± 4.5 mg/dl vs 54.9 ± 2.2 mg/dl)(p < 0.001) among JIA children as compared to control. The FF genotype was significantly more frequent in JIA (n = 35; 63.6%) than control(n = 19; 34.5%)(p < 0.001)(Odds ratio 3.3; CI 95% 1.5–7.2) while the Ff genotype was more in the control (n = 29; 52.7% vs n = 5; 9.1%)(p < 0.001). There were no significant variations in the lipid profile across VDR genotypes (p greater than 0.05).There was a significant association of FF genotype (n = 35; 100%) with the oligoarticular subtype of JIA and Ff (n = 3; 60%), ff (n = 9; 60%) with the polyarticular subtype of JIA (p < 0.001). ConclusionVDR FF genotype is associated with three folds risk for JIA and VDR polymorphism is not associated with dyslipidemia in JIA.

Associations of CXCL12 polymorphisms with clinicopathological features in breast cancer: a case-control study

BackgroundPrevious studies suggested that CXCL12 was involved in the development, metastasis, and invasion of breast cancer, and genetic variants were associated with the diagnosis and prognosis of patients with breast cancer. The present study was aimed to assess the relationships between CXCL12 polymorphisms (rs1801157, rs2297630, and rs2839693) and susceptibility and clinicopathological features of breast cancer.MethodsA case-control study was conducted in 434 breast cancer patients and 450 health controls. Student t-test and chi-square test were used to analyze the differences of age distribution and genotype frequencies between the two groups. Correlations between polymorphisms and clinical parameters were also assessed by chi-square test. The potential effects of the three polymorphisms on CXCL12 were investigated by the public database.ResultsA statistical association was found between CXCL12 rs1801157 polymorphism and breast cancer risk, possibility of metastasis, and estrogen receptor status. Patients with rs2839693 C/T or C/T-T/T genotypes were more likely to be progesterone receptor-negative. However, no associations of rs2297630 polymorphism with breast cancer risk or any clinicopathological characteristics were observed. In addition, rs2297630 affected the splicing quantitative trait loci of CXCL12 in the subcutaneous fat, rs2839693 polymorphism affected the splicing quantitative trait loci of CXCL12 in the human breast mammary tissues.ConclusionsThose results indicated that CXCL12 polymorphisms might be potential diagnostic indicators, and more investigation is needed in the future.

The association of dietary fibre intake and the IL13 rs20541 polymorphism with the risk of gastric cancer: a case-control study in Korea.

The beneficial effect of fibre intake on reducing the risk of gastric cancer (GC) has been emphasized in recent years; however, the findings from the existing literature have been ambiguous. Fibre and anti-inflammatory cytokines are associated with GC through inflammation. We investigated whether a higher fibre intake reduces GC risk and whether the IL13 rs20541 single-nucleotide polymorphism interacts with fibre intake to modify GC risk. In this case-control study, 377 cases and 756 controls were included to assess the effects of fibre intake and the IL13 rs20541-fibre interaction on GC risk. We collected information on fibre consumption by using a semi-quantitative food frequency questionnaire. The presence of IL13 rs20541 was determined through genetic analysis. A negative association between fibre intake and GC risk was observed (odds ratio (OR) = 0.37, 95% confidence interval (CI) = 0.24-0.57, P for trend < 0.001). However, the significant association seemed to be limited to males (OR = 0.28, 95% CI = 0.16-0.50, p for trend < 0.001). Although a non-significant association between IL13 rs20541 and GC risk was found (OR = 0.95, 95% CI = 0.71-1.26), we identified that individuals with a minor allele of IL13 rs20541 (AA/AG) and higher fibre intake had a lower GC risk than those with a minor allele and lower fibre intake (OR (95% CI) was 0.24 (0.12-0.45), P interaction = 0.024). Our findings suggested a protective effect of fibre against GC carcinogenesis. However, fibre intake seemed to have a greater effect in individuals with a minor allele of IL13 rs20541 (AA/AG).

Interleukin10 rs1800896 and interleukin1B rs16944 polymorphisms and the risk of cervical cancer.

The purpose of this study was to evaluate the relationships between interleukin10 (IL10) (rs1800896) and interleukin1B (IL1B) (rs16944) genetic polymorphisms and the risk for cervical cancer in acohort of women from Croatia. Acase-control study of 81patients with cervical cancer and 80age-matched healthy controls was performed. We collected peripheral blood samples, extracted deoxiribonucleic acid (DNA), and analyzed two single-nucleotide polymorphisms (SNPs) rs1800896 and rs16944 using TaqMan assays (Fa. Thermo Fisher Scientific, Waltham, MA, USA) and real-time polymerase chain reaction (PCR). We investigated apossible association between two cytokine genetic polymorphisms and the occurrence of cervical cancer. Our results showed no significant difference in the frequency of IL10 (rs1800896) and IL1B (rs16944) genotypes between the patients and the controls (χ2 test, P < 0.05). In this study, no association was found between IL10 rs1800896 and IL1B rs16944 polymorphisms and cervical cancer development.

DBP rs7041 and DHCR7 rs3829251 are Linked to CD4+ Recovery in HIV Patients on Antiretroviral Therapy.

Background: The lack of the recovery of CD4+ T-cells (CD4+ recovery) among immunodeficiency virus (HIV)-infected patients on antiretroviral therapy (ART) is not well known. We aimed to analyze the association between single nucleotide polymorphisms (SNPs) underlying vitamin D metabolism and the CD4+ recovery in naïve HIV-infected patients who started ART with low baseline CD4+. Methods: We conducted a retrospective study in 411 naïve individuals with plasma HIV load >200 copies/mL and CD4+ <200 cells/mm3. During 24 months of follow-up, all patients had plasma HIV load <50 copies/mL. DNA genotyping was performed using the Sequenom MassARRAY platform. The outcome variable was the change in CD4+ during the study. Results: CD4+ recovery was higher in patients carrying DBP rs7041 AA genotype (AA versus CC/AC) and DHCR7 rs3829251 AA genotype (AA versus GG/AG) (p-value < 0.05). DBP rs7041 AA genotype was linked to increase in CD4+ (adjusted arithmetic mean ratio (aAMR) = 1.22; q-value = 0.011), increase in CD4+ ≥P75th [adjusted odds ratio (aOR) = 2.31; q-value = 0.005], slope of CD4+ recovery (aAMR = 1.25; q-value = 0.008), slope of CD4+ recovery ≥ P75th (aOR = 2.55; q-value = 0.005) and achievement of CD4+ ≥500 cells/mm3 (aOR = 1.89; q-value = 0.023). Besides, DHCR7 rs3829251 AA genotype was related to increase in CD4+ (aAMR = 1.43; q-value = 0.031), increase in CD4+ ≥P75th (aOR = 3.92; q-value = 0.030), slope of CD4+ recovery (aAMR = 1.40; q-value = 0.036), slope of CD4+ recovery ≥ P75th (aOR = 3.42; q-value = 0.031) and achievement of CD4+ ≥500 cells/mm3 (aOR = 5.68; q-value = 0.015). Conclusion: In summary, DHCR7 rs3829251 and DBP rs7041 polymorphisms were associated with CD4+ recovery in HIV-infected patients who started cART with low CD4+ T-cell counts.

Pb and Cd exposure linked with Il-10 and Il-13 gene polymorphisms in asthma risk relevant immunomodulation in children

Genetic variants and environmental factor of heavy metal exposure accelerate the risk of immune-mediated respiratory diseases, including asthma in children. This study aims to investigate the effects and interaction of Pb, Cd exposure from e-waste and interleukin (IL)-10, IL-13 gene polymorphisms on interleukin expressions in children. Pb, Cd levels, Il-10 (rs1800871, rs1800872, rs1800896) and Il-13 (rs20541, rs1800925) polymorphisms were determined in blood or urine of 155 children (75 from e-waste-exposed area, Guiyu and 80 from reference area, Haojiang). Blood Pb and urine Cd levels of e-waste-exposed children were both higher (mean: 5.89 vs. 3.35 μg/dL; 6.04 vs. 1.82 μg/g, both P < 0.05). Exposed children had a larger proportion of high blood Pb level (> 5.00 μg/dL) (66.67% vs. 4.11%, P < 0.001), but they had no statistically different proportion of high urine Cd level (> 1.00 μg/g creatinine). Median levels of IL-13 decreased (3.674 vs. 4.410 ng/L, P < 0.01), but of IL-10 did not vary in serum of exposed children. The analyses revealed no significant associations of Pb or Cd with Il-10 or Il-13 gene polymorphisms. The high blood Pb and urine Cd level were respectively associated with the low IL-13 ( < 3.696 ng/L) and low IL-10 ( < 0.361 ng/L) level, after adjustment for children's age, gender, and BMI (both P ≤ 0.05). Children homozygous carrying major allele for Il-13 (rs20541 and rs1800925) had additive interactions with high blood Pb level on low IL-13 expression (OR = 5.37, 95% CI: 1.96, 14.73 and OR = 8.45, 95% CI: 2.61, 27.32; both P ≤ 0.001). In contrast, no interaction was observed amongst Pb or Cd with Il-10 gene polymorphisms on its expression. Our findings suggest that Pb exposure interacting with Il-13 gene polymorphisms negatively regulates IL-13 expression, which may pose a risk to abnormal asthma-relevant immunomodulation in preschool children.

Rs7041 and rs4588 Polymorphisms in Vitamin D Binding Protein Gene (VDBP) and the Risk of Diseases

The purpose of the study was to investigate the role of vitamin D binding protein (VDBP, DBP) and its polymorphism in the vitamin D pathway and human health. This narrative review shows the latest literature on the most popular diseases that have previously been linked to VDBP. Vitamin D plays a crucial role in human metabolism, controlling phosphorus and calcium homeostasis. Vitamin D binding protein bonds vitamin D and its metabolites and transports them to target tissues. The most common polymorphisms in the VDBP gene are rs4588 and rs7041, which are located in exon 11 in domain III of the VDBP gene. rs4588 and rs7041 may be correlated with differences not only in vitamin D status in serum but also with vitamin D metabolites. This review supports the role of single nucleotide polymorphisms (SNPs) in the VDBP gene and presents the latest data showing correlations between VDBP variants with important human diseases such as obesity, diabetes mellitus, tuberculosis, chronic obstructive pulmonary disease, and others. In this review, we aim to systematize the knowledge regarding the occurrence of diseases and their relationship with vitamin D deficiencies, which may be caused by polymorphisms in the VDBP gene. Further research is required on the possible influence of SNPs, modifications in the structure of the binding protein, and their influence on the organism. It is also important to mention that most studies do not have a specific time of year to measure accurate vitamin D metabolite levels, which can be misleading in conclusions due to the seasonal nature of vitamin D.

Gene polymorphism associated with FOXP3, CTLA-4 and susceptibility to pre-eclampsia: a meta-analysis and trial sequential analysis

Previous studies have detected the correlation of polymorphisms in regulatory T cells associated genes FOXP3 and CTLA-4 with pre-eclampsia (PE) risk, but the results are inconsistent among studies. Eligible studies were retrieved in several database. Odds ratios (ORs) with 95% confidence intervals (CIs) were utilised to evaluate the relationship between FOXP3 rs3761548, FOXP3 rs2232365, CTLA-4 rs231775 polymorphisms, and PE susceptibility in the genetic models. The subgroup analysis and trial sequential analysis were performed. Twelve studies with a total of 4658 participants were included. There was a statistically significant association between FOXP3 rs3761548 polymorphism and PE within the recessive model in Asian (OR = 0.54, 95% CI = 0.34–0.86). Trial sequential analysis indicated sufficient proof of such association in the Asian population. This meta-analysis provides sufficient statistical evidence indicating an association between FOXP3 rs3761548 polymorphism and PE risk in Asian. IMPACT STATEMENT What is already known on this subject? FOXP3 and CTLA4 are markers of regulatory T cells which play a crucial role during a preeclamptic pregnancy. What do the results of this study add? Eleven studies with a total of 4658 participants were included. There was a statistically significant association between FOXP3 rs3761548 polymorphism and pre-eclampsia (PE) within the recessive model in Asian (OR = 0.54, 95% CI = 0.34–0.86). Trial sequential analysis indicated sufficient proof of such association in the Asian population. However, there was no enough evidence could proof significant association between FOXP3 rs2232365 or CTLA-4 rs231775 polymorphism and PE. What are the implications of these findings for clinical practice and/or further research? This meta-analysis provides sufficient statistical evidence indicating an association between FOXP3 rs3761548 polymorphism and PE risk in Asian. The findings in this study may provide a basis for the further study on FOXP3 rs3761548 polymorphism in future research.

Analysis of Association between Interleukin-6 (&amp;lt;i&amp;gt;IL&amp;lt;/i&amp;gt;6), Interleukin-13 (&amp;lt;i&amp;gt;IL&amp;lt;/i&amp;gt;13) and Tumor Necrosis Factor-Alpha (&amp;lt;i&amp;gt;TNF-alpha&amp;lt;/i&amp;gt;) Gene Polymorphisms and Genetic Susceptibility of Rheumatoid Arthritis in Kuwaiti Arab

Background: Rheumatoid arthritis (RA) is a common autoimmune disease in which a combination of risk alleles from different susceptibility genes predisposes the patients to develop clinical symptoms following exposure to environmental factors. RA is a chronic and progressive disease characterized by synovial inflammation that results in destruction in the affected joints and severe problems in individual’s mobility. Several immune-related risk factors have been associated with RA, these include single nucleotide polymorphisms (SNPs) in cytokine genes. The impact of these cytokine gene polymorphisms is due to their association either with elevated serum levels and/or variations in their serum levels are associated with disease-onset and progression. The objective of this study was to investigate the role of Interleukin-6 (IL6), Interleukin-13 (IL13) and Tumor necrosis factor-alpha (TNF-alpha) gene polymorphisms in genetic susceptibility of RA in Kuwaiti patients. Methods: We have determined the genotypes of IL6 gene (-174G/C; rs1800795), IL13 gene (R130Q; rs20541) and TNF-alpha gene (-308A/G' rs1800629) polymorphisms in 192 Kuwaiti patients with RA and compared it to that in 104 healthy controls. The diagnosis of RA was based on the American College of Rheumatology (ACR) classification criteria. The genotypes for IL6, IL13 and TNF-alpha gene polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods and confirmed by DNA sequencing. Results: The frequency of IL6 gene (-174G/C; rs1800795) and TNF-alpha gene (-308A/G' rs1800629) polymorphisms manifested a statistically significant difference between Kuwaiti RA patients and controls (P = 0.02 and 0.002 respectively). In contrast, the frequency of IL13 gene (R130Q; rs20541) polymorphism did not show a significant difference between Kuwaiti RA patients and controls. Conclusions: Our data showed an association of two cytokine gene polymorphisms (i.e. IL6 gene -174G/C; rs1800795 polymorphism, and TNF-alpha gene -308A/G, rs1800629 polymorphism) with RA in Kuwaiti patients highlighting their significant contribution in genetic susceptibility of this chronic disease possibly along with other factors.

Association between VDR Gene Polymorphisms and Melanoma Susceptibility in a Colombian Population.

Background:The vitamin D receptor (VDR) is responsible for mediating the effects of vitamin D through regulation of other gene transcriptions. There are several polymorphisms that alter the gene expression or the function of this protein. We aimed to analyze the association between two SNPs of VDR gene and melanoma cancer in Colombian patients. Methods:We included 120 healthy individual as controls and 120 melanoma cancer patients as cases . Patients in both groups were matched in terms of gender and age. The genotyping of rs731236 and rs2228570 polymorphisms was performed using PCR-RFLP. The SNPStats program was used to carry out the statistical analysis through a logistic regression model.Results: Under dominant model, we found that rs2228570 polymorphism was associated with melanoma cancer risk (C/C vs C/T-T/T, OR: 5.10, 95% CI: 2.85-9.14), whereas rs731236 polymorphism was associated with a protective effect against this cancer (T/T vs T/C, OR: 0.27, 95% CI: 0.14-0.53). Conclusion:Our results suggested that both polymorphisms were involved in the development of melanoma cancer, increasing or decreasing this risk.

Investigating the association of toll-like receptor 9 rs5743836, rs352140, and rs187084 gene polymorphisms and their mRNA levels with different hepatic fibrosis stages of non-alcoholic fatty liver patients compared to healthy controls.

Recent studies have shown that the level of hepatocyte-derived mitochondrial DNA is elevated in plasma samples obtained from mice and NASH patients, and it has the ability to toll-like receptor 9 (TLR9) activation resulting in steatosis, hepatocyte injury, and fibrosis. In this study, we explored the association between TLR9 rs5743836, rs352140, and rs187084 polymorphism and its plasma mRNA level in non-alcoholic fatty liver (NAFL) patients with different liver fibrosis scores compared to healthy controls. Seventy Iranian patients diagnosed with NAFL, based on fibroscan testing results, were divided into F0-F1 (N=33), F2-F3 (N=19), and F4 (N=18) hepatic fibrosis groups and compared to 22 healthy controls. Genotyping was done using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the mRNA expression level of TLR9 was determined using Real-Time PCR analysis. Results showed no significant association between allelic and genotypic distribution frequency of TLR9 rs5743836, rs352140, and rs187084 polymorphisms in NAFL patients with hepatic fibrosis compared to healthy controls (P>0.05). However, the mRNA level of TLR9 was significantly elevated in correlation with hepatic fibrosis progression in NAFL patients compared to healthy controls (P<0.05). As a preliminary study, our data showed a correlative overexpression of TLR9 mRNA with hepatic fibrosis progression in NAFL patients without the effectiveness of TLR9 gene polymorphisms.

Association between interleukin 12B and interleukin 23R gene polymorphisms and systemic lupus erythematosus: a meta-analysis.

ObjectiveTo determine whether polymorphisms of interleukin 12B (IL12B) and IL23 receptor genes (IL23R) confer susceptibility to systemic lupus erythematosus (SLE).MethodsA meta-analysis was conducted to analyze the associations between SLE and IL12B rs3212227 and rs17860508 and IL23R rs7517847, rs10489629, rs10889677, rs1004819, rs11209026, rs11209032, rs1343151, and rs1884444 polymorphisms using allele contrast, dominant, recessive, heterozygote, and homozygote models. Ten studies involving 1989 patients with SLE and 2394 controls were considered for the meta-analysis.ResultsThe meta-analysis using the homozygote model revealed that IL23R rs10889677 was significantly associated with SLE susceptibility in the overall population (AA vs. CC) (odds ratio = 0.70, 95% confidence interval = 0.50–0.98) but not in the Asian population. Other polymorphisms of IL12B and IL23R were not significantly associated with SLE protection.ConclusionsThese findings suggest that the IL23R rs10889677 polymorphism confers SLE susceptibility to individuals of certain ethnicities. (Research Registry number: 1268)

RESULTS OF FREQUENCY ANALYSIS DISTRIBUTION OF A1188C RS3212227 POLYMORPHISM IN THE IL 12B GENE AMONG PATIENTS WITH CHRONIC RHINOSINUSITIS POLYPOSIS

Analyzing the prevalence of genotypic variants of this polymorphism, we revealed a direct association of the C/C monogenotype of the A1188C rs3212227 polymorphism in the IL12B gene with the development of polyposis processes. In addition, these data emphasize the prognostic significance of the C/C genotype of the rs1800896 polymorphism of the IL-12B gene in the development of CPMS. In carriers of this genotype, the relative risk of developing CPMS increases by more than 3 times, compared with carriers of other genotypic variants of the rs3212227 polymorphism of the IL12B gene.

Associations of IL-6 polymorphisms with Behçet’s Disease in Denizli, province of Turkey

Behçet's Disease is a chronic, multisystemic disease and the etiopathogenesis of the disease develop as a result of the interaction of environmental and genetic factors. IL-6 is a proinflammatory cytokine with functions on immune response regulation and chronic inflammation demonstrated by increased serum levels and gene expression studies in Behçet’s disease. We genotyped IL-6; rs1800797, rs1800796 and rs1800795 polymorphisms in 78 patients with Behçet’s disease and 130 healthy controls using PCR-RFLP based approach. No statistically significant difference in allele or genotype frequencies of IL-6, rs1800797 and rs1800796 was found in between groups. We determined that in the BD patients with genital ulcers, arthritis and without vascular involvement was found to have significantly different IL-6, SNP frequencies compared with healthy controls. In addition, the IL-6 rs1800795 GC genotype and C allele may contribute to the development of the disease in female BD. The haplotype distributions of all loci of IL-6 were examined and GGG was found as the highest frequency haplotype in both groups. In conclusion, the results of our study showed that IL-6 rs1800795 may associate with the susceptibility to the BD. Studies should be conducted with more SNPs in large and different populations need to evaluate the contribution of responsible alleles for the disease and its clinical features.

Implication of single nucleotide polymorphisms in Interleukin-10 gene (rs1800896 and rs1800872) with severity of COVID-19

BackgroundCoronavirus disease 2019 (COVID-19) is an ongoing pandemic which has emerged as a new challenge for the medical sciences. Severity of COVID-19 is mostly determined with overexpressed proinflammatory cytokines eventually leading to endothelial dysfunction causing vital organ injury, especially in the lungs. It has been postulated that various genetic mutations might be associated with an increased risk of disease severity in COVID-19. This study was thus carried out to determine the association of rs1800896 and rs1800872 genetic polymorphism in IL-10 gene in determining COVID-19 severity.MethodsThe study included 160 RT-PCR confirmed COVID-19 patients with mild (n = 85) and severe (n = 75) conditions. All subjects were genotyped for Interleukin-10 (rs1800896 and rs1800872) gene polymorphisms using PCR–RFLP technique followed by statistical analysis.ResultsThis study found a significant gender and age-based discrepancy in COVID-19 severity with 1.85-and 3.81-fold increased risk of COVID-19 in males of mild and severe groups as compared to females (p = 0.046 and p < 0.001) and 4.35-fold high risk in subjects ≥ 50 (p < 0.001). Genotyping analysis showed that IL-10 (rs1800872) gene polymorphism was strongly associated with COVID-19 severity (p = 0.01) whereas, IL-10 rs1800896 polymorphism was not found to confer the risk of COVID-19 severity in our population.ConclusionIn this regard, the present study provided an evidence that IL-10 (rs1800872) gene polymorphism is strongly associated with COVID-19 severity and CC genotype confer a protective role in preventing severe disease progression. More detailed studies with a larger sample size on the genetic variations are required to establish the role of studied IL-10 gene polymorphisms with COVID-19 severity.

Association of Inherited Genotype and Severity of Clinical Presentation in Subjects with Verified Pas III Disorder.

Background:Polyglandular autoimmune syndrome type III (PAS III) is combination two most common autoimmune disease: Diabetes mellytus type 1 (DM1) and autoimmune thyroid disease (AITD).Objectives:The aims of the study were a) to define conection between polymorphism of CTLA-4 gene, rs 231775 with PAS III; b) to establish the conection of inherited genotype with severity of clinical features; and c) to estimate the rate of risk for severe clinical presentation among subgroups in study population.Methods:This research included 50 subjects with diagnosed PAS III syndrome, wich are on treatment in clinic for Nuclear medicine and andocrinology KCUS. As methods of research has used: hystory of disesase AND clinical examination. As material is used blood sample. From blood sample DNA was isolated withn Qiamp- DNA-mini kit, with accopanied protocol.Results:In our study, 50 patients with polyglandular autoimmune syndrome type III (PAS III) were examined, and in the study population had 26 female subjects and 24 male subjects. The average age of the participants was 31.64 years, and in the subgroups: group GWT (G-wild type) the average age was 30.20 years, group GM (G-mutated) 32.40 years and group GH (G-heterozygote) 30 , 60 years. Using the Chi-square test, the association between the polymorphism rs231775 and PAS-III was demonstrated, x2 (2.100) = 18.258, where p < 0.0001. Using the Chi-square test, the association between the rs231775 polymorphism and the severity of the clinical picture, x2 (2.50) = 8.531, where p< 0.0140 was proved. The CTLA-4 rs231775 genotypes were also assessed for disease severity.Conclusion:This study suggests that CTLA-4 expression plays a key role in balancing the immune system as well as the response against one’s own tissues, and thus in the regulation of autoimmune diseases.

STAT4 gene polymorphism as a risk factor for hepatocellular carcinoma on top of chronic hepatitis C

BackgroundSingle-nucleotide polymorphism in the STAT4 gene was strongly associated with the risk of hepatocellular carcinoma (HCC) progression in patients chronically infected with hepatitis C virus (HCV).ObjectiveTo study the effect of STAT4 gene (rs7574865) polymorphism on HCC in complicating chronic hepatitis C.Patients and methodsOne hundred and fifty individuals were divided into three groups. The studied participants were divided into three groups. Group I: 50 apparently healthy individuals served as controls. They were completely free clinically with normal laboratory investigations, normal abdominal ultrasonography, and no history of liver and renal disease. Group II: 50 chronic HCV patients confirmed by HCV-antibodies and PCR HCV RNA analysis. Group III: 50 HCV-induced HCC patients confirmed by computed tomography and serum alpha-fetoprotein. Most of the patients are males with a mean age of 54 years. Real-time PCR analysis to determine STAT4 (rs7574865) gene polymorphism was performed on DNA extracted from all the studied participants.ResultsComparing the three studied groups, there was highly significant statistical difference regarding genotype and allele frequency distribution with a GG genotype of 20% in the control group, 46% in the HCV group, and 56% in the HCC group with a P value less than 0.001. GT genotype is 50% in the control group, 44% in the HCV group, and 38% in the HCC group. There were statistically significant differences in STAT4 (rs7574865) allele frequencies between the patient group (HCC and HCV as one group) and the control group (P < 0.001) [GG: odds ratio (OR)=9.562, 95% confidence interval (CI)=3.204–28.541, GT: OR = 3.075, 95% CI = 1.141–8.290]. Allele association study revealed a significant risk association between allele type and cancer development (OR = 3.066, 95% CI = 1.861–5.053).ConclusionThe results suggested that STAT4 (rs7574865) GG genotype is associated with HCC development in Egyptians with chronic HCV infection.

Association between the IL-6 polymorphisms and coal workers’ pneumoconiosis in a Chinese Hui population

ObjectiveTo determine whether polymorphisms in IL-6 and IL-12 contribute to the etiology of coal workers’ pneumoconiosis (CWP) in a Chinese Hui population, and to evaluate the efficacy and safety of high frequency oscillatory ventilation (HFOV) in the treatment of CWP.IntroductionGenes and the environments interplay in the development of CWP, and the association between the potential functional polymorphisms in many genes and CWP have been reported.MethodsWe genotyped the IL-6-634C/G (rs1800796) and IL-12B-1188A/C (rs3212227) polymorphisms in a case-control study including 160 CWP patients and 150 dust-exposed control subjects of Chinese Hui population, and analyzed the associations between these genetic variants and CWP risk. We also evaluated the efficacy and safety of HFOV for whole lung lavage (WLL) in the treatment of CWP.ResultsCarrying the C allele of IL-6-634C/G (rs1800796) was associated with decreased risk of CWP ( p &lt; 0.05). No significant differences in allele or genotype frequencies of IL-12B-1188A/C was found between the CWP cases and control subjects ( p &gt; 0.05). Compared with CWP patients with routine WLL, CWP patients received HFOV showed better pulmonary functions. HFOV treatment also yield a significant higher efficient rate (97.50%) than WLL treatment (81.25%, p = 0.001). CWP patients receiving HFOV and WLL treatment both showed significantly increased serum contents of Clara cell protein 16 (CC16) and superoxide dismutase (SOD), and decreased serum contents of serum malonaldehyde (MDA). While the increasing of CC16 and SOD, and decreasing of MDA in patients receiving HFOV was more noticeable than patients receiving WLL.ConclusionsTaking together, the −634C/G polymorphisms in IL-6 play a role in the etiology of CWP. HFOV, when applied in CWP patients, significant improves their pulmonary functions.