Rs1800629 Polymorphism Research Articles

Association of IL-6 rs1800795 and IL-1 β rs16944 polymorphisms with non-small cell lung cancer in the Egyptian population: a pilot study

Association of IL-6 rs1800795 and IL-1 β rs16944 polymorphisms with non-small cell lung cancer in the Egyptian population: a pilot study

Vitamin D receptor rs3782905 and vitamin D binding protein rs7041 polymorphisms are associated with hepatocellular carcinoma susceptibility in cirrhotic HCV patients

BackgroundThe severity of chronic hepatitis C and susceptibility to hepatocellular carcinoma (HCC) are associated with genetic variations within vitamin D receptor (VDR) in several populations. This study aims to determine the significance of the VDRs (rs2228570, rs3782905, rs11568820) and DBP (rs7041) for the susceptibility to HCC in Egyptian patients with chronic HCV infection and their effect on the progression of liver cirrhosis to carcinogenesis.MethodsSingle nucleotide polymorphisms (SNPs) VDR (rs2228570, rs3782905), and DBP rs7041 were genotyped using restriction fragment length-PCR (RFLP-PCR) technique and VDR rs11568820 was genotyped using single strand polymorphism PCR (SSP PCR). These SNPs genotypes, haplotypes and linkage disequilibrium analyses were examined in 299 Egyptian individuals (100 HCV-cirrhotic patients, 99 HCC- HCV patients, and 100 healthy controls).ResultThe VDR rs2228570 CC genotype, VDR rs3782905 GC and CC genotypes, and DBP rs7041 GG genotype are significantly higher in HCC. It is noteworthy that, VDR rs3782905 CC and DBP rs7041 TG genotypes are higher in HCV induced liver cirrhosis than with HCC progression in HCV infected patients. Furthermore, among patients, the relationship between these SNPs and smoking status, gender, and HCC susceptibility was reported.ConclusionAmong the four investigated SNPs, there are associations between VDR rs3782905 and DBP rs7041 and the HCC progression in Egyptian patients chronically infected with HCV. These SNPs are considered as risk factors in HCV induced liver cirrhosis and HCC. The combinations of these SNPs with smoking status and gender are statistically linked to a high risk of HCC. Future research with a larger sample size of subjects with HCV infection is advised, because chronic liver disease induced by HCV infection is the primary cause of HCC in Egypt. We recommend screening of these SNPs for prediction of LC and HCC development in HCV infected patients, which may improve the used therapeutic protocol. These results suggest that VDR polymorphisms may be potential determinants for HCC susceptibility in Egyptian HCV patients.

Impact of IL-6 rs1800795 and IL-17A rs2275913 gene polymorphisms on the COVID-19 prognosis and susceptibility in a sample of Iranian patients

BackgroundFrom asymptomatic to acute and life-threatening pulmonary infection, the clinical manifestations of COVID-19 are highly variable. Interleukin (IL)-6 and IL-17A are key drivers of hyper inflammation status in COVID-19, and their elevated levels are hallmarks of the infection progression. To explore whether prognosis and susceptibility to COVID-19 are linked to IL-6 rs1800795 and IL-17A rs2275913, these single-nucleotide polymorphisms (SNPs) were assessed in a sample of Iranian COVID-19 patients. MethodsThis study enrolled two hundred and eighty COVID-19 patients (140 non-severe and 140 severe). Genotyping for IL-6 rs1800795 and IL-17A rs2275913 was performed using tetra primer-amplification refractory mutation system-polymerase chain reaction (tetra-ARMS-PCR). IL-6 and IL-17A circulating levels were measured using enzyme-linked immunosorbent assay (ELISA). Also, mortality predictors of COVID-19 were investigated. ResultsThe rs1800795 GG genotype (78/140 (55.7 %)) and G allele (205/280 (73.2 %)) were significantly associated with a positive risk of COVID-19 severe infection (OR = 2.19, 95 %CI: 1.35–3.54, P =.006 and OR = 1.79, 95 %CI: 1.25–2.56, P <.001, respectively). Also, rs1800795 GG genotype was significantly linked to disease mortality (OR = 1.95, 95 %CI: 1.06–3.61, P =.04). The rs2275913 GA genotype was protective against severe COVID-19 (OR = 0.5, 95 %CI: 0.31––0.80, P =.012). However, the present study did not reveal any significant link between rs2275913 genotypes with disease mortality. INR ≥ 1.2 (OR = 2.19, 95 %CI: 1.61–3.78, P =.007), D-dimer ≥ 565.5 ng/mL (OR = 3.12, 95 %CI: 1.27–5.68, P =.019), respiratory rate ≥ 29 (OR = 1.19, 95 %CI: 1.12–1.28, P =.001), IL-6 serum concentration ≥ 28.5 pg/mL (OR = 1.97, 95 %CI: 1.942–2.06, P =.013), and IL-6 rs1800795 GG genotype (OR = 1.95, 95 %CI: 1.06–3.61, P =.04) were predictive of COVID-19 mortality. ConclusionThe rs1800795 GG genotype and G allele were associated with disease severity, and INR, D-dimer, respiratory rate, IL-6 serum concentration, and IL-6 rs1800795 GG genotype were predictive of COVID-19 mortality.

IImmunological parameters in patients with chronic opisthorchiasis bearing gene mutations associated with osteoporosis-predisposition

To identify the features of the immune system functioning in patients with chronic opisthorchiasis bearing mutations in loci associated with predisposition to developing osteoporosis, comprehensive studies of cellular and humoral arms were carried out. The state of the phagocytic system was assessed by assessing absorption, metabolic activity and reactive oxygen species formation to restore nitrosine tetrazolium (spontaneous and stimulated NBT test). The phenotype of lymphocytes was determined by flow cytometry. The humoral immune arm was evaluated by the number of immunoglobulin classes M, G, A and E. Differences in the functional state of various arms of the immune system were revealed. In patients with chronic opisthorchiasis in the presence of rs1544410 polymorphism of the gene encoding the intracellular vitamin D receptor, the relative number of T-helper cells is significantly lower than in the group with the normal allele. In the presence of rs1800012 polymorphism of the gene encoding the α1-chain of type I collagen, the absolute lymphocyte count is significantly higher, spontaneous and stimulated NBT test were lower, the number of DN-T lymphocytes is significantly lower (both in relative and absolute values). In the presence of the rs3736228 mutation of the gene encoding the transmembrane low-density lipoprotein receptor, the level of myeloperoxidase and the neutrophil stimulation index are lower, the absorption activity of neutrophils is higher. The presence of the rs2234693 mutation for estrogen receptor gene leads to significantly increased level of stimulated NBT test and IgG concentration. Thus, patients with chronic opisthorchiasis bearing mutations in the COL1 A1, LRP5, ESR1(rs2234693) genes, have altered both nonspecific innate reactions and parameters of the adaptive immune arm; mutation of the VDR gene solely affects adaptive immunity. Analysis of the results suggests that the presence of mutations associated with the development of osteoporosis has a modulating effect on the immune response in chronic opisthorchiasis invasion. The identification of polymorphic genes associated with metabolic disorders of bone tissue and the study of the immunological profile in patients with chronic opisthorchiasis invasion will allow to implement an individual approach in the treatment of such patients.

Relationship Between Human FCγRIIA rs1801274 G Allele and Risk of Death Among Different SARS-CoV-2 Variants.

Coronavirus disease 2019 (COVID-19), the illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 and spread very quickly across the world. Different responses to infections have been related to fragment crystallizable gamma-receptor II alpha (FcγRIIA) polymorphisms. The purpose of this investigation was to determine if FCγRIIA rs1801274 polymorphism was related to COVID-19 mortality among different variants of SARS-CoV-2. The FCγRIIA rs1801274 polymorphism was genotyped using the polymerase chain reaction-restriction fragment length polymorphism technique in 1,734 recovered and 1,450 deceased patients. Deceased patients had significantly higher minor allele frequency of the FCγRIIA rs1801274 G allele than in the recovered cases. The COVID-19 mortality was associated with FCγRIIA rs1801274 GG and AG genotypes in the Delta variant and with FCγRIIA rs1801274 GG genotypes in the Alpha and Omicron BA.5 variants. The reverse transcription-quantitative polymerase chain reaction Ct values revealed statistically significant differences between individuals with a G allele and those with an A allele. In conclusion, among the several SARS-CoV-2 variants, there may be a correlation between the mortality rate of COVID-19 and the G allele of FCγRIIA rs1801274. To confirm our findings, thorough research is still required.

Interleukin-1β gene rs1143634 polymorphism and cardiovascular complications in patients with coronary artery atherosclerosis

The course of heart failure, regardless of its etiology, is associated with local and systemic activation of inflammatory signaling cascades. Identification of the association of candidate cytokine genes with the risk of developing coronary heart disease and chronic heart failure remains a subject of interest for many researchers. The review presents an analysis of studies of the rs1143634 polymorphism of the IL-β gene in relation to the risk of atherosclerotic cardiovascular complications. The presence of the minor allele T is associated with an increase in the concentration of IL-1β in the blood serum. Data on the role of the rs1143634 polymorphism of the IL-β gene in atherosclerotic coronary heart disease, including in combination with chronic heart failure syndrome, are presented, taking into account ethnic characteristics and gender of patients. The carriage of the T allele was associated with the risk of developing atherosclerosis and myocardial infarction. At the same time, it is reported that the C allele and the CC genotype of the rs1143634 polymorphism of the IL-1β gene were a genetic risk factor for the development and progression of heart failure. In a number of studies and meta-analyses, the association of this polymorphism with diseases of the cardiovascular system was not confirmed, but certain trajectories of the risk of complications were identified due to differences in the rs1143634 polymorphism of the IL-β gene in heart failure.

Interleukins-6 −174G/C (rs1800795) and −572C/G (rs1800796) polymorphisms and prostate cancer risk

Prostate cancer (PCa) is an aggressive cancer influenced by a complex interplay of genetic and environmental factors. Amongst these risk factors, the impact of Interleukin6 (IL6) gene polymorphisms in PCa risk has received a lot of attention. IL-6 is a cytokine that has been implicated in the pathogenesis of several malignancies, including PCa. Two IL-6 gene polymorphisms, − 174 G/C (rs1800795) and − 572 C/G (rs1800796), have received intellectual attention due to their potential role as modulators of prostate cancer risk. The main objective of this research was to comprehensively explore the potential associations between IL-6 rs1800795 and rs1800796 polymorphisms, and their impact on the occurrence of PCa. A case-control study was carried out with a well-defined cohort comprising 110 PCa cases and 110 controls (total n = 220). The genotyping of rs1800795 and rs1800796 was carefully performed using the highly sensitive and accurate Polymerase Chain Reaction-High Resolution Melting Curve (PCR-HRM) technique. The assessment of genetic associations was evaluated using various R packages, such as Haplo-Stats, SNP stat, pheatmap, and LD heatmap. The present study applied odds ratio (OR) analysis to reveal significant evidence of strong associations between the genotypes of rs1800795 and rs1800796 and the susceptibility to PCa. The findings of this study underscore the noteworthy impact of genetic variations in the IL-6 gene on the development of prostate cancer. Specifically, the C/G and G/G genotypes of rs1800795 demonstrated increased PCa risk, with odds ratios (OR) of 1.650 (95% CI = 1.068–2.549, p = 0.032) and 2.475 (95% CI = 1.215–5.043, p < 0.001), respectively. Similarly, the G/C genotype of rs1800796 exhibited an OR of 2.374 (95% CI = 1.363–4.130, p = 0.012) for elevated prostate cancer risk, while the C/C genotype had an OR of 1.81 (95% CI = 1.02–3.22, p = 0.7). Furthermore, our haplotype analysis have revealed an association between haplotype 4 (C-G) and increased risk of PCa (OR = 1.69, 95% CI = 1.05–2.73, p = 0.032). In conclusion, this case-control analysis presents compelling evidence for a significant association between IL-6 variants (rs1800795 and rs1800796) and increased susceptibility to prostate cancer.

The effect of genetic variation and mRNA expression of interleukin-17A gene on susceptibility to asthma.

Analyzing the genetic variation and mRNA expression of interleukin-17A (IL-17A) gene and its impact on asthma susceptibility was the purpose of this study. 120 asthma patients were selected as the asthma group, and another 120 healthy individuals who underwent physical examination were selected as the health group; Compare the cytokine levels and mRNA expression of IL-17A between two groups, as well as the clinical indicator total immunoglobulin E (TIgE) levels; The genotype and allele distribution frequency of IL-17A Single-nucleotide polymorphism locus rs2275913 and rs8193036 were compared between the two groups; Compare the serum IL-17A and TIgE levels of different genotypes at rs2275913 and rs8193036 loci; and logistic regression was used to evaluate the impact of IL-17A on asthma susceptibility. The serum levels of IL-17A, TIgE, and IL-17AmRNA expression in the asthma group were higher than those in the healthy group (P<0.05). There were three genotypes of AA, AG and GG at rs2275913 locus, and the frequency distribution between the two groups was significant (P<0.05), and the frequency of A Allele frequency in asthma group was higher than that in healthy group (P<0.05). There are three genotypes of CC, CT, and TT at the rs8193036 locus, and there was no significant difference in the frequency distribution between the two groups (P>0.05). There is no difference in the frequency distribution of alleles C and T between the two groups (P>0.05). The levels of IL-17A and TIgE in the rs2275913AA genotype were higher than those in the AG and GG genotypes (P<0.05); There was no difference in IL-17A and TIgE levels among different genotypes of rs8193036 (P>0.05). The rs2275913 polymorphism was associated with asthma susceptibility and is an independent risk parameter for asthma susceptibility. Upregulation of serum IL-17A and TIgE, as well as overexpression of IL-17A mRNA, were closely related to asthma susceptibility in asthma patients. The rs2275913 polymorphism had a significant role in increasing the risk of asthma, and variant allele A may be a susceptibility factor for increasing asthma risk.

PPARA and IL6: exploring associations with athletic performance and genotype polymorphism.

This study aims to investigate the Interleukin (IL)-6 rs1800795 and peroxisome proliferator-activated receptor alpha (PPARA) rs4253778 polymorphism distributions in the relatively faster and slower subgroups of national cross-country skiing athletes and to identify advantageous genotypes for endurance performance. IL-6 is an inflammatory mediator that is effective in muscle tissue hypertrophy, repair, and the immune system. On the other hand, PPARA transcription factor is a molecule associated with fatty acid, sugar metabolism and inflammation formation. Total of 30 professional cross-country skiing athletes were examined in three groups as athletes, female athletes, and male athletes. DNA of the participants were isolated from blood and genetic polymorphisms were determined by RT-PCR. Athletes were divided into two subgroups as faster and slower referring to their "1-kilometer cross-country skiing time averages (CCSTA)". Polymorphism distributions in these subgroups were analyzed statistically with Fisher's exact test and descriptive tests. In addition, the 1 km-CCSTA values of the genotypes were determined by descriptive statistical methods and the time advantages were calculated. It was determined that the combination of IL-6 rs1800795 GC and PPARA rs4253778 GG genotypes was observed to be more prominent among the faster categories of cross-country skiing competitors, particularly in the athletes and male athletes categories, and it had a time advantage at 1 km-CCSTA. The GC genotype (p= 0.0098) and C-allele (p=0.0398) of IL-6 rs1800795 polymorphism were detected at a higher rate in the fast subgroup in male athletes. These genotypes may support endurance performance.

Association between IL10 rs1800896 polymorphism and risk of pediatric asthma: A meta-analysis.

Asthma is a common chronic condition in children. Several studies have explored the potential association between IL10 rs1800896 polymorphism and the risk of asthma in children, but the findings have been inconsistent. To address these discrepancies, we conducted a systematic review and meta-analysis to assess the relationship between IL10 rs1800896 polymorphisms and the susceptibility to pediatric asthma. A literature search was conducted in PubMed, Scopus, Web of Science, and CNKI databases to identify eligible studies through April 2022. Meta-analysis was then performed using five genetic models: dominant, recessive, homozygous, heterozygous, and allele. A total of 12 studies comprising 1645 cases along with 1447 controls were included in this meta-analysis. It was found that rs1800896 was not associated significantly with susceptibility to childhood asthma in all genetic models investigated. Subgroup analysis based on the ethnic background of the subjects revealed that rs1800896 was significantly linked to a lower risk of pediatric asthma among Asians in the homozygous model (OR = 0.311, 95% CI = 0.152-0.637, P = 0.001) and in the recessive model (OR = 0.585, 95% CI = 0.405-0.846, P = 0.004), whereas no significant relationship was observed in Egyptians (P > 0.05). In conclusion, IL10 rs1800896 polymorphism may be useful as a predictive marker for childhood asthma in Asians, although further studies are needed to validate the study results.

Distribution of human gene polymorphisms allele frequencies associated with viral infections.

The design of studies aimed at finding the association between the genetic factor and the studied feature (disease) involves a comparison of the ratio of genotypes or allelic proportions in the study group with those in the control group. At the stage of determining the ratio of genotypes of the studied polymorphisms in the reference group, researchers meet a number of problems, which are the subject of the present work. Aim of the work is to provide scientific rationale for the feasibility of creating a national information system comprising genetic data of the relatively healthy population of Russia, incorporating its ethnic diversity. The study group, total 1020 people, was genotyped for a number of single nucleotide polymorphisms of human genes. A comparative characteristic of the frequency distribution of the studied polymorphisms with those presented in international databases as reference data was carried out using χ2 index. The frequency of SNP rs4986790 of the TLR4 gene significantly differs from the EUR population (p = 0.032) and the CEU subpopulation (p = 0.047). The allele frequencies of the rs1800795 (IL6) and rs1800896 (IL10) polymorphisms in the study population differ from the CEU subgroup (p = 0.030 and 0.012, respectively). The frequency of SNP rs2295119 (HLA-DPA2) in the study group is significantly different from the EUR population (p = 0.034). The analysis carried out in this work confirms the need to create a domestic information system containing data on the occurrence of SNP alleles and genotypes for a conditionally healthy population and in subgroups with various pathological conditions.

The association of cytokines genes (IL-6 and IL-10) with the susceptibility to schizophrenia: A systematic review and meta-analysis

Cytokines are among the important effectors and messenger molecules for restoring the homeostasis tissue after an inflammatory response. The association between IL-6 and IL-10 genes polymorphisms with the schizophrenia susceptibility have yielded controversial results. To reconcile the results, a systematic review followed by meta-analysis was performed to assess the association. We carried out literature searches of PubMed, Scopus, EBSCO, and Web of Sciences databases. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to assess the strength of the association. Subgroup analysis, heterogeneity analyses, and publication bias were also calculated in the meta-analysis. A total of 22 case-control studies, consisting of 4,993 schizophrenic patients and 5,195 healthy controls, were included in the meta-analysis. The meta-analysis suggests that the IL-6 rs1800795 polymorphism displays a protective role against schizophrenia, while the IL-10 rs1800896 and rs1800872 polymorphisms confer an increased risk of schizophrenia. Similar results were found in subgroup analysis by ethnicity. We did not find association between IL-10 rs1800871 polymorphism and schizophrenia susceptibility. Finally, this meta-analysis suggested that the dysregulation of cytokines could lead to the pathogenesis of the schizophrenia.

IL-6 gene polymorphism predicts PEGylated IFN-α treatment response in hepatitis B surface antigen-positive chronic hepatitis B patients.

Background: Genetic polymorphism can affect the response to antiviral therapy of chronic hepatitis B (CHB) patients. Objective: The study examined the genetic association of the IL-6 rs1800796 polymorphism with PEGylated IFN-α (PegIFN-α) treatment response in hepatitis B surface antigen (HBsAg)-positive CHB patients. Methods: Direct sequencing was done for the genotyping of the rs1800796 polymorphism in the serum of CHB patients. Results: More patients with combined response (n=95) carried IL-6 rs1800796 GC genotypes, while CC genotype carriers possessed reduced HBeAg seroconversion rate and high values of hepatitis B virus DNA. Baseline HBsAg and HBeAg and IL-6 rs1800796 CC genotype were independently related to PegIFN-α treatment response. Conclusion: Detection of the IL-6 rs1800796 genotype in CHB patients may have potential guiding significance for PegIFN-α response.

Association analysis between the VDR gene variants and type 2 diabetes.

Type 2 diabetes mellitus (T2DM) is recognized as a complex metabolic which has affected the lives of millions of people around the world. Vitamin D receptor (VDR) gene polymorphisms have been suggested to be a vital contributor to the development of T2DM. However, the association between VDR gene polymorphisms and T2DM remains controversial.We have investigated the association between two VDR gene polymorphisms (rs731236 and rs1544410) and T2DM in an Iranian population. A total of 148 T2DM patients and 100 normal controls were recruited in this study. We used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis to perform genotyping. The results of the present research revealed that the frequency of the rs731236 C allele was significantly higher in T2DM patients than in normal controls (p = 0.044). The CC genotype of rs731236 was connected with an increased risk of T2DM (OR = 2.85, 95% CI = 1.06-7.69, p = 0.039). However, no significant difference in the frequency of the rs1544410 C allele between T2DM patients and normal controls was observed (p = 0.918). Our findings were suggestive of the rs731236 polymorphism of the VDR as a risk factor for developing T2DM in the Iranian population, while rs1544410 polymorphism may not be associated with T2DM susceptibility. Further research is needed to approve these findings in other populations and to clarify the underlying mechanisms involved in such an association. The online version contains supplementary material available at 10.1007/s40200-023-01323-0.

Association between course of multiple sclerosis and polymorphisms of calcitriol receptor gene VDR FokI (rs2228570), BSMI (rs1544410), TaqI (rs731236), ApaI (rs7975232)

Objective. To evaluate the relationship between the frequency of exacerbations and the rate of progression of multiple sclerosis (MS) and polymorphisms of the calcitriol receptor gene VDR FokI (rs2228570), BSMI (rs1544410), TaqI (rs731236), ApaI (rs7975232).Material and methods. Ninety patients with relapsing-remitting MS took part in the study. All patients are Caucasians, were born and lived in the Altai region of the Russian Federation. Genotyping was performed by TaqMan probes.Results. A protective effect of the TT genotype VDR FokI (rs2228570) on the risk of increasing disability of more than 0.75 points per year according to the expanded disability scale was found (p = 0.034). The protective effect of the TT genotype of the TaqI polymorphism (rs731236) on exacerbations of MS more than once a year (p = 0.041) was also revealed. Associations of the MS course with other studied polymorphisms were not found.Conclusions. It can be assumed that the VDR FokI (rs2228570) and TaqI (rs731236) polymorphisms may influence the course of relapsing-remitting MS. The mechanisms of these influences may include the modulation of immune-inflammatory responses in the central nervous system, which are a key link in the MS pathogenesis.

Cardiovascular and microvascular outcomes according to vitamin D level and genetic variants among individuals with prediabetes: a prospective study

BackgroundWhether serum vitamin D mediate vascular diseases in prediabetic populations remains unclear. This study aimed to determine the associations between circulating 25-hydroxyvitamin D [25(OH)D] levels and vitamin D receptor (VDR) polymorphisms with the risk of macrovascular complications, including myocardial infarction and stroke, and microvascular complications such as diabetic nephropathy and retinopathy, among adults with prediabetes.MethodsParticipants with prediabetes in UK Biobank were included (N = 56,387). Multivariable dose–response and Cox proportion models were used to explore the relationship of serum 25(OH)D status and the risks of vascular complications. The interaction of VDR polymorphisms with serum 25(OH)D level on risks of vascular events was also assessed.ResultsDuring a median follow-up of 12 years, higher levels of 25(OH)D were significantly and nonlinearly associated with a lower risk of macrovascular diseases among prediabetic individuals. The adjusted hazard ratios (95% confidential interval) of serum 25(OH)D levels of ≥ 75.0 nmol/L versus < 25 nmol/L were 0.75 (0.63–0.88) for myocardial infarction, 0.74 (0.55–1.00) for stroke, 1.02 (0.60–1.74) for diabetic nephropathy, and 1.30 (0.92–1.84) for diabetic retinopathy, respectively. The rs2228570 (FokI) polymorphisms significantly interacted with 25(OH)D on incident myocardial infarction (P-interaction = 0.042) and stroke (P-interaction = 0.033). The individuals with serum 25(OH)D level of 50.0–74.9 nmol/L and rs2228570 (FokI) homozygotes had the lowest risks of vascular complications.ConclusionsLower serum 25(OH)D levels are significantly and nonlinearly associated with an increased risk of cardiocerebrovascular diseases in prediabetic individuals, with VDR polymorphisms of rs2228570 (FokI) modify such associations. Monitoring a safe 25(OH)D concentration is suggested to prevent the vascular complications for prediabetes.

Association between PYTPN22 rs2476601, VEGF rs833070, TNFAIP3 rs6920220 Polymorphisms and Risk for Rheumatoid Arthritis in Early Undifferentiated Arthritis Patients: A Pilot Study.

Background and Objectives: About 40% of early undifferentiated arthritis (UA) progresses to rheumatoid (RA) or other chronic arthritis. Novel diagnostic tools predicting the risk for this progression are needed to identify the patients who would benefit from early aggressive treatment. Evidence on the role of single-nucleotide polymorphisms (SNPs) in the development of RA has emerged. The aim of our study was to investigate the association between rs2476601, rs833070, and rs6920220 SNPs and UA progression to RA. Materials and Methods: Ninety-two UA patients were observed for 12 months. At study entry, demographic and clinical characteristics were recorded, musculoskeletal ultrasonography was performed, and blood samples were drawn to investigate levels of inflammatory markers, rheumatoid factor (RF), anti-citrullinated protein antibodies (anti-CCP)detect SNPs. After 12 months, UA outcomes were assessed, and patients were divided into two (RA and non-RA) groups. The association between the risk of progression to chronic inflammatory arthritis and analyzed SNPs was measured by computing odds ratios (OR). Results: After a 12-month follow-up, 27 (29.3%) patients developed RA, and 65 (70.7%) patients were assigned to the non-RA group. The arthritis of 21 patients (22.8%) from the non-RA group resolved completely, while the other 44 (47.2%) patients were diagnosed with another rheumatic inflammatory disease. The patients who developed RA had a significantly greater number of tender and swollen joints (p = 0.010 and p = 0.021 respectively) and were more frequently RF or anti-CCP (p < 0.001), and both RF and anti-CCP positive (p < 0.001) at the baseline as compared with the patients in the non-RA group. No significant association between rs2476601 (OR = 0.99, p = 0.98), rs833070 (OR = 1.0, p = 0.97), and rs6920220 (OR = 0.48, p = 0.13) polymorphisms and the risk of developing RA were found. Conclusions: No association between analyzed SNPs and a greater risk to progress from UA to RA was confirmed, although patients with rs6920220 AA + AG genotypes had fewer tender joints at the disease onset.

Association of IL-17 and IL-27 polymorphisms with susceptibility to recurrent pregnancy loss and pre-eclampsia: A systematic review and meta-analysis.

Recurrent pregnancy loss (RPL) and pre-eclampsia (PE) are immune-related pregnancy complications that have been linked to CD4+ T cells and their cytokines, which can be influenced by genetic polymorphisms. This meta-analysis aimed to investigate the relationship between interleukin (IL)-17 and -27 polymorphisms and the susceptibility to RPL and PE. All eligible case-control studies published up to February 2023 were identified by searching PubMed, EMBASE, Cochrane, Web of Science, and Google Scholar. The risk of recurrent pregnancy loss and PE associated with the IL-17 rs2275913, IL-17 rs763780, IL-27 rs153109, and IL-27 rs17855750 polymorphisms were estimated for each study. The meta-analysis incorporated a total of 13 studies. The overall analysis indicated that IL-17 rs2275913, IL-17 rs763780, IL-27 rs153109, and IL-27 rs17855750 polymorphisms were not significantly associated with immune-related pregnancy complications, including RPL and PE. However, when the analysis was stratified by disease type, the IL-17 rs2275913 polymorphism was found to be associated with an increased risk of RPL (recessive model AA/GA + GG: OR = 1.68, 95% confidence interval [CI]: 1.13-2.49, p = .01). The IL-17 rs763780, IL-27 rs153109, and IL-27 rs17855750 polymorphisms were not significantly associated with RPL and PE, whereas the IL-17 rs2275913 polymorphism was associated with the susceptibility to recurrent miscarriage.

Association between interleukin-12B gene polymorphisms and multiple sclerosis in turkish population

Elevated levels of IL-12p40 have been observed in the cerebrospinal fluid and serum of MS patients, and it has been suggested that genetic variants in the IL-12B gene may contribute to MS susceptibility and/or pathogenesis. In this study, we investigated the association between MS and IL-12B gene rs17860508 and rs3212227 polymorphisms in the Turkish population. We identified two polymorphic regions in the IL-12B gene using bioinformatics tools and genotyped 351 MS patients and 221 healthy controls for these variants. Our results showed a significant association between the IL-12B rs17860508 polymorphism and MS, but no significant relationship between rs17860508 genotype distribution and allele frequency and MS age onset or subtypes. Genotype distribution and allele frequency of IL-12B rs3212227 polymorphism did not show any significant association with MS directly. However, AC genotype of IL-12B rs3212227 polymorphism in early-onset multiple sclerosis (EOMS) was a risk factor according to age of onset. Additionally, we observed a higher risk for the relapsing-remitting multiple sclerosis (RRMS) subtype in females. This is the first study to investigate the association between IL-12B polymorphisms and MS in the Turkish population.

PREDICTION OF THE RISK OF SEVERE PERITONITIS IN ACUTE INFLAMMATORY DISEASES OF THE ABDOMINAL CAVITY

Abstract. Introduction. One of the most challenging problems of surgery is peritonitis, which can be a complication of acute inflammatory diseases of the abdominal cavity and is accompanied by high mortality. The development of prognostic models of peritonitis is a modern task of precision medicine.&#x0D; Aim. To determine the risk of severe peritonitis in patients undergoing surgery for acute abdominal diseases.&#x0D; Materials and methods. The study involved 139 patients who had been operated on for acute abdominal diseases (acute appendicitis and cholecystitis, perforated gastric or duodenal ulcer, etc.). Depending on the number of points on the modified APACHE II scale, patients were divided into two groups: Group 1 - 1-3 points (63 patients, 45.3%) and Group 2 - 4 or more points (76 patients, 54.7%). The rs1927911, rs2149356 and rs4986790 polymorphisms were determined by polymerase chain reaction using the Gene Amp® PCR System 7500 amplifier (Applied Biosystems, USA) and TaqMan Mutation Detection Assays Life-Technology (USA). Statistical processing of the study results was performed using the EZR v.1.54 software (Vienna, Austria).&#x0D; Results. Univariate regression analysis revealed a higher (p=0.008) risk of severe peritonitis for men (OR 2.56; 95% CI 1.29-5.11) compared with women; an increase (p=0.031) in the risk of severe peritonitis with patient age (OR 1.02; 95% CI 1.00-1.05). The risk of severe peritonitis increased (p&lt;0.05) with higher admission temperature, heart rate, international normalised ratio, and leukocytosis. A reduction (p=0.009) in the risk of severe peritonitis was found with a higher prothrombin index (OR 0.95; 95% CI 0.92-0.99). In addition, a decrease (p=0.015) in the risk of severe peritonitis was found in carriers of the G/A+A/A rs1927911 heterozygote of the TLR4 gene (OR 0.42; 95% CI 0.21-0.84) compared with carriers of the ancestral G/G genotype. The multivariate model included the rs1927911 genotype, age, sex, heart rate, and leukocytosis (AUC=0.83; 95% CI 0.75-0.89; p&lt;0.001); the model sensitivity was 68.4% (95% CI 56.7%-78.6%), and specificity was 88.9% (95% CI 78.4%-95.4%).&#x0D; Conclusion. Thus, prognostic risk factors for severe peritonitis were identified and a mathematical model for its prediction was developed using clinical, laboratory and genetic parameters.