Rs1800629 Polymorphism Research Articles

Assessing the Impact of TLR4 rs4986790 Polymorphism on Bacterial Meningitis Risk: A Systematic Review and Meta-Analysis.

Toll-like receptor (TLR2) gene plays an important role in the pathogenesis of bacterial meningitis (such as meningococcal meningitis and pneumococcal meningitis). The association between TLR4 rs4986790 polymorphism and the susceptibility to bacterial meningitis has been extensively studied. However, the results of these studies remain inconsistent. Therefore, we performed a meta-analysis to evaluate the association between TLR4 rs4986790 polymorphism and the susceptibility to meningococcal meningitis and pneumococcal meningitis. Google Scholar, Embase, and PubMed databases were searched for case-control studies on TLR4 polymorphisms and the risks of meningococcal meningitis and pneumococcal meningitis, published up to May 31, 2024. To assess the strength of the association between TLR4 polymorphism and meningococcal meningitis and pneumococcal meningitis, the odds ratios (ORs) with 95% confidence intervals (CIs) were used. The meta-analysis of the associations between the TLR4 rs4986790 polymorphism and meningococcal meningitis and pneumococcal meningitis was carried out under different genetic models. Meta-analyses were conducted using Cochrane RoB 2 tool and Metagenyo to calculate the ORs and 95% CIs. Fourteen published studies with 3599 cases and 7438 controls were included. Overall, there was a strong correlation between TLR4 polymorphisms and meningococcal meningitis observed across three genetic models using a random-effects model: GG + GA vs. AA (OR: 0.34, 95% CI: 0.14-0.79, P = 0.01, I² = 60%); GA vs. AA (OR: 0.34, 95% CI: 0.13-0.91, P = 0.03, I² = 65%); and GG vs. AA (OR: 0.34, 95% CI: 0.14-0.78, P = 0.01, I² = 59%). Conversely, a fixed-effects model also revealed a significant association in the G vs. A model (OR: 0.84, 95% CI: 0.73-0.96, P = 0.01, I² = 38%). In pneumococcal meningitis, a fixed-effects model analysis demonstrated a significant association in the GG vs. AA model (OR: 0.35, 95% CI: 0.14-0.87, P = 0.02, I² = 48%) respectively. This meta-analysis showed a strong correlation between TLR4 rs4986790 polymorphism and susceptibility to meningococcal meningitis and pneumococcal meningitis. Further studies with diverse populations are needed to validate and strengthen these findings.

Impact of IL-6 rs1800795 and rs1800796 polymorphisms on clinical outcomes of COVID-19: a study on severity of disease in Turkish population.

Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is exacerbated by cytokine storms, leading to severe inflammation. Interleukin-6 (IL-6) plays a critical role in this process, and variations in its promoter may influence disease severity. This study aims to investigate the relationship between IL6 promoter polymorphisms rs1800795 (G > C) and rs1800796 (G > C) and the severity of COVID-19 in the Turkish population. A total of 332 participants were included: 84 control, 80 with mild COVID-19, and 168 with severe COVID-19. IL6 polymorphisms were genotyped using the restriction fragment length polymorphism (RFLP) method. The genotypes rs1800795 GC (OR = 3.00, 95% CI: 1.669-5.398, p < 0.000), CC (OR = 7.44, 95% CI: 2.899-19.131, p < 0.000), and rs1800796 GC (OR = 2.76, 95% CI: 1.603-4.761, p < 0.000), as well as the alleles rs1800795 C (OR = 3.01, p < 0.000) and rs1800796 C (OR = 1.97, p = 0.002), may be associated with the severity of COVID-19. According to the Jonckheere-Terpstra (J-T) test, the most significant trends that vary linearly with disease severity were observed for D-dimer [J-T = 15.896, Effect size = 0.68 (0.61 to 0.76), p < 0.000] and CRP [J-T = 15.389, Effect size = 0.66 (0.59 to 0.73), p < 0.000]. The distribution of clinical parameters across genotype combinations (rs1800796/rs1800795*) showed that GC/GC* and GC/CC* were linked to a higher risk of severe inflammation, clotting, and organ damage. Additionally, it has been determined that the G-C and C-C haplotypes may be associated with increased severity of COVID-19. The rs1800795 and rs1800796 polymorphisms are linked to COVID-19 severity and could help guide future treatment strategies.

The association of the rs4588 and rs7041 polymorphisms of the VDBP gene and vitamin D status in obese individuals

BACKGROUND: Vitamin D (VD) plays an important role in bone metabolism, regulating phosphorus and calcium in the body. The VD binding protein (VDBP) binds to VD metabolites and transports them to the target tissues; it is assumed that polymorphisms of this gene influence the absorption of VD in the body. However, the relationship between polymorphisms of the VDBP gene and blood VD levels in obesity has not yet been sufficiently investigated. AIM: To identify the relationship of blood VD content (form 25(OH)D3) of obese and non-obese persons and the VDBP gene polymorphisms rs4588 and rs7041. METHODS: 80 residents of the Kaliningrad region participated in the study. The participants were divided according to VD status (norm, insuffient, deficiency and severe deficiency) and body mass index (BMI). Blood VD levels were determined using an ELISA. Genomic DNA was isolated from whole blood. Restriction analysis was performed with the endonucleases HaeIII and ErhI to determine the VDBP gene polymorphisms. RESULTS: There were no significant differences in blood VD levels of obese and non-obese individuals. Within the genotypes of the rs4588 polymorphism (CA), VD levels did not differ in individuals with different BMI (CС p=0.186; CA p=0.350, AA data is insufficient). However, when analyzing the allele frequencies in groups with different VD status, a significant difference was found in all groups compared to the control (insufficient p=0.009; deficiency p=0.010; severe deficiency p0.001). When analyzing the rs7041 polymorphism of the VDBP gene (TG), splitting groups by BMI within specific genotypes did not reveal differences in VD levels (TG p=0.150; GG p=0.087; TT data is insufficient), but we found a significant difference between control and severe deficiency (p0.001) based on allele frequencies of the rs7041 polymorphism. CONCLUSION: The VD content in blood of the obese individuals was comparable to that of the control group. The presence of the VDBP gene rs7041 and rs4588 polymorphisms has no influence on blood VD level, regardless of BMI. However, allele A of the rs4588 polymorphism is associated with an unfavorable VD status, while allele G of the rs7041 polymorphism is associated with normal blood VD levels.

Impact of gene polymorphisms involved in the vitamin D metabolic pathway on the susceptibility to and severity of autism spectrum disorder

This study explores the association between genetic variations in the vitamin D pathway and autism spectrum disorder (ASD) susceptibility and severity in Thai children. A total of 276 participants, including 169 children with ASD and 107 healthy controls, were recruited. Genotyping of vitamin D pathway genes (CYP2R1, CYP27B1, GC, and VDR) was conducted using TaqMan-based real-time PCR, while serum vitamin D levels were measured by chemiluminescence immunoassay. ASD severity was assessed via the Childhood Autism Rating Scale, 2nd Edition. Results reveal that the VDR gene (ApaI) rs7975232 is linked to a reduced ASD risk. In contrast, the GC gene rs7041 (A > C) polymorphism shows a significant association with increased ASD risk and severity, particularly in individuals with both the GC gene polymorphism and vitamin D insufficiency. Additionally, there was a higher prevalence of the GC1s isoform and GC1s-GC1s haplotype in children with ASD, associated with ASD severity. This study identified that individuals possessing GC rs7041 C alleles and the GC1s genotype (rs7041C/rs4588G) exhibit an increased susceptibility to and more severity of ASD. Further studies with larger cohorts are essential to fully understand these genetic polymorphisms’ roles.

A Meta-Analysis of Association Between Interleukin Polymorphisms (rs4073, rs1800925, rs1179251, rs1179246, rs2227485, rs17855750, and rs153109) and Colorectal Cancer Risk.

Interleukins (ILs) play a significant role in triggering the inflammatory response in blood vessels and immune cells. A systematic review and meta-analysis were conducted to investigate the relationship between IL-8 (rs4073), IL-13 (rs1800925), IL-22 (rs1179251, rs1179246, and rs2227485), and IL-27 (rs17855750 and rs153109) polymorphisms and the risk of developing colorectal cancer (CRC). Four databases were searched up until October 13, 2023, without any restrictions, to find relevant studies. The association was evaluated using crude odds ratios (ORs) and 95% confidence intervals in five genetic models. A total of twenty-three articles were entered into the meta-analysis. The pooled ORs (p-values) for the IL-8 (rs4073) polymorphism were 0.98 (0.63), 0.93 (0.44), 0.89 (0.13), 0.94 (0.38), and 0.99 (0.90) for studies following HWE without heterogeneity, and for all studies with high heterogeneity were 1.03 (0.69), 1.30 (0.07), 1.04 (0.71), 1.12 (0.20), and 1.23 (0.06). For the IL-13 (rs1800925) polymorphism, the pooled ORs were 1.44 (0.06), 2.58 (0.0004), 1.72 (0.16), 1.82 (0.09), and 2.37 (0.001) in AHHDR models, respectively. The pooled ORs of IL-22 (rs1179251) polymorphism for AHHDR models were 0.97 (0.92), 0.92 (0.90), 0.98 (p = 0.95), 1.08 (0.87), and 0.96 (0.82), respectively. The pooled ORs of IL-22 (rs1179246) polymorphism for AHHDR models were 0.98 (0.67), 0.97 (0.80), 0.92 (0.36), 0.93 (0.42), and 1.02 (0.84), respectively. The pooled ORs of IL-22 (rs2227485) polymorphism for AHHDR models were 1.47 (0.02), 2.03 (0.02), 1.28 (0.29), 1.52 (0.06), and 1.70 (0.04), respectively. The pooled ORs of IL-27 (rs17855750) polymorphism for AHHDR models were 0.53 (0.46), 0.19 (0.28), 1.10 (0.60), 0.55 (0.58), and 0.27 (p = 0.05), respectively. The pooled ORs of IL-27 (rs153109) polymorphism for AHHDR models were 1.28 (0.007), 1.45 (0.002), 1.40 (0.0002), 1.41 (< 0.0001), and 1.20 (0.09), respectively. The results reported that just the TT genotype of IL-13 (rs1800925), the T allele and TT genotype of IL-22 (rs2227485), and the G allele and GG, AG and GG + AG genotypes of IL-27 (rs153109) polymorphisms had an elevated risk in CRC patients.

The effect of the TNFα gene rs1800629 polymorphism on cytokine profile parameters in the complicated wound healing in combat trauma victims

Background. In the wound process, there is a high probability of complications in the form paratraumatic eczema (РТЕ), which determines the severity the course of wound repair. Genetic factors responsible for the regulation of cytokines a leading role in the etiopathogenesis of РТЕ. Aim — determine the relationship of TNFa gene rs1800629 with the development of РТЕ and IL-1ß, TNFα, IL-6. Materials and methods. The study included 162 patients after surgical interventions. Group I — 82 people with complications in the form PTE and II — 80 people without complications. The study rs1800629 TNFα gene was carried out by the poly- merase chain reaction method. The levels TNFα, IL-1β and IL-6 in the blood was determined by the enzyme immunoassay method. Results. A connection with PTE was established with of rs1800629 gene TNFα (p = 0.033 and p = 0.005). The genotypes GA (OR = 1.64; CI 0.83–3.24) and AA (OR = 2.94; CI 0.9–9.67), allele A (OR = 2.13; CI 1.26–3.6) rs1800629 influenced the increased chances of developing PTE. In group II the IL- 1β, TNFα, IL-6 indicators were increased (p &lt; 0.001) in carriers of the AA genotype rs1800629. Conclusion. rs1800629 TNFα gene is associated with development of PTE. An increase in the levels IL-1β, TNFα, IL-6 was associated with the presence of a pathogenetic factor — AA genotype rs1800629 TNFα gene in development of complications.

The impact of CTLA-4 gene polymorphism on the content of organ-specific antibodies in patients with autoimmune thyroiditis among the population of Azerbaijan

BACKGROUND: The risk of developing immune tolerance to self-antigens in autoimmune thyroiditis is largely associated with a mutation in the CTLA-4 gene, the product of which negatively regulates T-cell activity. AIM: To study the A49G (rs231775) CTLA-4 polymorphism in patients with autoimmune thyroiditis in a sample of Azerbaijani residents and the effect of the frequency of identified alleles and genotypes on the level of antibodies to thyroid peroxidase and thyroglobulin. MATERIAL AND METHODS: A study was conducted in 2021–2023 involving 170 patients with autoimmune thyroiditis and 65 individuals without thyroid pathology or other autoimmune diseases, who formed a comparison group. The groups were matched by gender and age. Based on the patient history, thyroid status study results, thyroid ultrasound data, and organ-specific antibody assessment, the patients were diagnosed with autoimmune thyroiditis. The routine thyroid status study results in the comparison group were within normal limits. Genotyping of the A49G (rs231775) polymorphism was performed using polymerase chain reaction followed by digestion of the reaction product with PspEI restriction endonuclease. The results of the quantitative studies were presented as the median (Me) and interquartile range (25th quartile; 75th quartile). The correspondence of genotype frequencies to the Hardy–Weinberg equilibrium was assessed using the χ2 criterion. RESULTS: The results revealed a statistically significant increase in the frequency of the G allele (48%) compared to the control group [33.8%; p=0.039, χ2=4.27, odds ratio (OR) 1.865, 95% confidence interval (CI) 1.028–3.382] and a decrease in the frequency of the A allele (51.2%) relative to the control group (66.1%; p=0.0389, χ2=4.27, OR=0.536, CI=0.296–0.973). In 22.4% of patients with the GG genotype (p=0.005, χ2=7.86, OR=0.237, 95% CI=0.088–0.635) and 55.6% of patients with the G allele (p=0.0012, χ2=10.43, OR=0.360, 95%, CI=0.192–0.674), thyroglobulin antibody titers were more than 100 IU/ml. Thyroid peroxidase antibody levels of 100 IU/ml or more were recorded in 22.7% of study participants with the GG genotype (p=0.030) and 50.0% with the G allele (p=0.048). CONCLUSION: Elevated titers of antibodies to thyroid peroxidase and thyroglobulin were detected in patients from the population of Azerbaijan with the G allele and homozygous genotype GG of the +49A/G polymorphism of the CTLA-4 gene.

Associations Between Interleukin-10 Polymorphisms and Susceptibility to Sjögren's Syndrome: A Meta-Analysis.

This study sought to investigate the association between interleukin-10 (IL10) polymorphisms and susceptibility to Sjögren's syndrome. A systematic search of the Medline, Embase and Web of Science databases was conducted to identify relevant articles from inception to April 2024. No restrictions were placed on race, ethnicity or geographic area, but only studies published in English were included. A meta-analysis was conducted to evaluate the association among the IL10-1082 G/A (rs1800896), -819 C/T (rs1800871) and -592 C/A (rs1800872) polymorphisms, as well as their haplotypes and the risk of developing Sjögren's syndrome. The included studies involved 998 Sjögren's syndrome patients and 1576 controls. Ten studies were included in the meta-analysis. Meta-analysis of the IL10-1082 G/A polymorphism revealed no significant association with Sjögren's syndrome (odds ratio [OR]=1.115, 95% confidence interval [CI]: 0.888-1.401, p=0.343), with stratification by ethnicity yielding consistent results for Europeans and Latin Americans. Similarly, the IL10-819 C/T polymorphism was not associated with Sjögren's syndrome in any study subjects (OR=0.859, 95% CI: 0.648-1.138, p=0.290). The IL10-592 C allele also exhibited no association with Sjögren's syndrome (OR=1.131, 95% CI: 0.776-1.646, p=0.522). However, the GCC carrier status demonstrated a significant association with Sjögren's syndrome across all study subjects (OR=1.496, 95% CI: 1.200-1.865, p<0.001), particularly in Europeans (OR=1.444, 95% CI: 1.085-1.921, p=0.012) and Latin Americans (OR=1.324, 95% CI: 1.115-2.366, p=0.012). A significant protective effect of the homozygous ATA/ATA haplotype on Sjögren's syndrome was found in Europeans (OR=0.320, 95% CI: 0.121-0.846, p=0.022). This meta-analysis indicates a significant link between carrying the GCC haplotype of the IL10-1082 G/A, -819 C/T and -592 C/A polymorphisms and an increased susceptibility to Sjögren's syndrome. Conversely, the homozygous ATA/ATA haplotype appears to confer protection against the risk of Sjögren's syndrome, particularly in European populations.

Genetic Variability in Oxidative Stress, Inflammatory, and Neurodevelopmental Pathways: Impact on the Susceptibility and Course of Spinal Muscular Atrophy

The spinal muscular atrophy (SMA) phenotype strongly correlates with the SMN2 gene copy number. However, the severity and progression of the disease vary widely even among affected individuals with identical copy numbers. This study aimed to investigate the impact of genetic variability in oxidative stress, inflammatory, and neurodevelopmental pathways on SMA susceptibility and clinical progression. Genotyping for 31 genetic variants across 20 genes was conducted in 54 SMA patients and 163 healthy controls. Our results revealed associations between specific polymorphisms and SMA susceptibility, disease type, age at symptom onset, and motor and respiratory function. Notably, the TNF rs1800629 and BDNF rs6265 polymorphisms demonstrated a protective effect against SMA susceptibility, whereas the IL6 rs1800795 was associated with an increased risk. The polymorphisms CARD8 rs2043211 and BDNF rs6265 were associated with SMA type, while SOD2 rs4880, CAT rs1001179, and MIR146A rs2910164 were associated with age at onset of symptoms after adjustment for clinical parameters. In addition, GPX1 rs1050450 and HMOX1 rs2071747 were associated with motor function scores and lung function scores, while MIR146A rs2910164, NOTCH rs367398 SNPs, and GSTM1 deletion were associated with motor and upper limb function scores, and BDNF rs6265 was associated with lung function scores after adjustment. These findings emphasize the potential of genetic variability in oxidative stress, inflammatory processes, and neurodevelopmental pathways to elucidate the complex course of SMA. Further exploration of these pathways offers a promising avenue for developing personalized therapeutic strategies for SMA patients.

VDR gene polymorphisms rs731236 and rsS2228570 affect vitamin D levels in people of the Kaliningrad region

Vitamin D is an essential micronutrient that is involved in numerous biological processes. It not only keeps bones healthy, but also has a protective effect on the cardiovascular system, the pancreas and fatty tissue. Around 50% of the world’s population suffers from vitamin D deficiency or insufficiency. The prevalence of these diseases is significantly higher in obese people, regardless of age and place of residence. The presence of polymorphisms in the VDR gene (vitamin D receptor) can explain individual differences in the concentration of vitamin D 25(OH) in blood serum. Of particular interest are the effects of the polymorphisms rs731236 and rs2228570 on vitamin levels. Thus, the VDR polymorphism rs731236 is a synonymous substitution, whereas the polymorphism rs2228570 is a non-synonymous substitution. The article investigated the polymorphisms of the VDR gene rs2228570 (T/C), rs731236 (T/C) and determined their association with blood vitamin D levels in people from the Kaliningrad region with different body mass index (BMI). The material for the study was venous blood taken in the morning on an empty stomach from 232 people (mean age 50±13.5 years, 103 men and 129 women). The vitamin D content in the blood was determined by ELISA and the polymorphisms of the VDR gene were analyzed by PCR. In individuals with a BMI 30 kg/m2, changes in the lipid profile and liver function tests were recorded. The vitamin D level did not depend on the BMI of the study participants. Significant changes in blood vitamin D levels were found depending on the distribution of the VDR genotype. Vitamin D levels were higher in individuals with the CC genotype than in the TT and CT genotypes of the rs2228570 polymorphism and did not depend on BMI. In contrast, the presence of the rs731236 polymorphism in the VDR gene is associated with BMI. In obesity, vitamin D levels are therefore only reduced in people with the TT genotype of the rs731236 polymorphism, but not in people with the CC and TC genotype.

Association of IL-6 G-174C (rs1800795) variant with the susceptibility to hepatocellular carcinoma in patients with chronic hepatitis

AimAn ineffective immune response resulting from dysregulation of cytokine production might encourage viral persistence and cause chronic viral hepatitis to worsen. This study examined the relationship between alterations in interleukin-6 (IL-6) levels and the IL-6 − 174 G > C (rs1800795) polymorphism, as well as how this polymorphism affects the development and progression of chronic hepatitis brought on by hepatitis B (HBV) and hepatitis C (HCV) into hepatocellular carcinoma (HCC).Patients and methodsWhole blood samples from 126 Egyptian patients with HCC (111 with HCV and 15 with HBV), as well as 126 age- and sex-matched healthy individuals, were used to extract DNA. Using PCR-based allele-specific amplification (ASA), the existence of the IL-6 G-174C polymorphism was investigated. Additionally, each participant's serum IL-6 levels were determined using an enzyme-linked immunosorbent assay (ELISA).ResultsThe primary observations revealed that HCC patients had greater serum levels of IL-6 compared to the control groups (p < 0.001). Patients with the variant (CG and GG) genotype in the HCC group were found to have more disease severity indicated by higher levels of alpha-fetoprotein (AFP) and a higher ascites grade, as well as increased inflammatory activity as defined by higher levels of IL-6 and C-reactive protein (CRP) (p < 0.001 for both) in comparison to patients with the wild-type (CC) genotype (p < 0.001 and p = 0.002, respectively).ConclusionThe rs1800795 SNP in the IL-6 gene was associated with increased inflammatory activity and high levels of IL-6, indicating that this SNP may play a role in the development of HCC in Egyptian patients with chronic viral hepatitis.

Role of Interleukin-17F Gene Polymorphism in Susceptibility to Acute Myeloid Leukemia: Relation to Serum Level of IL-17

Abstract Background The pathogenesis of acute myeloid leukemia (AML) is complex and not fully understood. A variety of interleukins have been shown to regulate the survival, growth, and apoptosis of leukemia cells. The IL-17 family includes interleukin-17F [rs763780; A7488G]. The IL-17F rs763780 polymorphism inhibits the wild-type IL-17F's activity and raises tumor susceptibility contributing to the emergence of certain tumor types including AML. Objectives This work aimed to study the relation between IL-17F gene polymorphism and susceptibility to AML and evaluated IL-17 plasma levels in AML with different IL-17F genotypes. Results There was no statistically significant difference in the distribution of different IL-17F genotypes between cases and controls. While the statistical comparison between both groups showed a significant difference with p-value &amp;lt;0.001 regarding IL-17 plasma level being higher in the case group with cutoff value &amp;gt;35 ng/L. Conclusion We concluded that IL-17 gene polymorphism doesn’t increase susceptibility to AML in Egyptian adults. IL-17 plasma level is an excellent diagnostic biomarker in AML patients.

Role of Genetic Polymorphisms -238 G>A and -308 G>A, and Serum TNF-α Levels in a Cohort of Mexican Pediatric Neuroblastoma Patients: Preliminary Study.

The results of in vitro and in vivo studies have shown the pro-tumor effects of TNF-α, and this cytokine's increased expression is associated with poor prognosis in patients with some types of cancer. Our study objective was to evaluate the possible association of TNF-α genetic polymorphisms and serum levels with susceptibility and prognosis in a cohort of Mexican patients with NB. We performed PCR-RFLP and ELISA methods to analyze the genetics of these SNPs and determine serum concentrations, respectively. The distribution of the -308 G>A and -238 G>A polymorphisms TNFα genotypes was considerably different between patients with NB and the control group. The SNP rs1800629 GG/GA genotypes were associated with a decreased risk of NB (OR = 0.1, 95% CI = 0.03-0.393, p = 0.001) compared with the AA genotype, which was associated with susceptibility to NB (OR = 2.89, 95% CI = 1.45-5.76, p = 0.003) and related to unfavorable histology and high-risk NB. The rs361525 polymorphism GG genotype was associated with a lower risk of developing NB compared with the GA and AA genotypes (OR = 0.2, 95% CI = 0.068-0.63, p = 0.006). Circulating TNF-α serum concentrations were significantly different (p < 0.001) between patients with NB and healthy controls; however, we found no relationship between the analyzed TNF-α serum levels and SNP genotypes. We found associations between the rs1800629AA genotype and lower event-free survival (p = 0.026); SNP rs361525 and TNF-α levels were not associated with survival in patients with NB. Our results suggest the TNF-α SNP rs1800629 as a probable factor of NB susceptibility. The -308 G/A polymorphism AA genotype has a probable role in promoting NB development and poor prognosis associated with unfavorable histology, high-risk tumors, and lower EFS in Mexican patients with NB. It should be noted that it is important to conduct research on a larger scale, through inter-institutional studies, to further evaluate the contribution of TNF-α genetic polymorphisms to the risk and prognosis of NB.

Interleukin-6 Receptor Gene rs1800795 Polymorphism and Expression of Interleukin-6 in Gingival Tissue in Patients with Periodontitis.

Periodontitis is a multifactorial inflammatory disease. This chronic periodontal disease is caused by a bacterial infection in the gums, which triggers a host inflammatory response. To eliminate the bacterial infection, immune response mechanisms are activated, leading to inflammation and damage to the periodontal tissues. This process involves many cytokines, including IL-6, a cytokine with antibacterial properties. An ongoing bacterial infection in the periodontal tissues leads to its excessive production, which increases inflammation. In this study, we examined IL-6 receptor gene rs1800795 polymorphism in patients with periodontitis in comparison with healthy subjects, as well as the correlation between rs1800795 genotypes and clinical parameters. Additionally we examined the expression of IL-6 in gingival tissue in patients with periodontitis and control subjects, as well as the correlation between gingival expression of IL-6 and clinical parameters. This study included 200 patients with periodontitis and 158 healthy subjects as the control group. Biopsy specimens of gingival tissue in which IL-6 expression was detected were taken from 14 patients with periodontitis and 8 controls who had undergone minor surgery. There were no statistically significant differences in the distribution of IL-6 rs1800795 genotypes and alleles between patients with periodontitis and control subjects. There were also no statistically significant correlations between IL-6 rs1800795 genotypes and clinical parameters in patients with periodontitis. There were no differences in IL-6 expression in the gingival tissue between patients with periodontitis and controls. There was also no correlation between IL-6 expression in the gingival tissue of patients with periodontitis and clinical parameters. In the control group, IL-6 expression in gingival tissue correlated negatively with the approximal plaque index, which reflects the size of bacterial plaques. The results of our study suggest a protective role for IL-6 against bacterial growth in the periodontal tissue. However, it should be noted that several parameters directly or indirectly affect the accumulation of bacterial plaque.

Association of Gene Polymorphisms with Polycystic Ovary Syndrome: A Meta-analysis

Objectives: Polycystic ovary syndrome (PCOS) is a prevalent endocrine-metabolic disorder affecting reproductive-aged women. Genetic factors play a significant role in its development. This meta-analysis assesses the associations between specific gene polymorphisms (Vitamin D receptor [VDR] and adiponectin [ADIPOQ]) and PCOS susceptibility. Materials and Methods: We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, Collecting data from published articles between 2013 to 2013. Eligible studies were selected based on inclusion and exclusion criteria, with quality assessment performed using the Newcastle–Ottawa scale. Data were extracted, and statistical analyses included odds ratios with 95% confidence intervals for gene polymorphisms. Heterogeneity was evaluated using I 2 tests, and publication bias was assessed using Begg’s and Egger’s tests. Results: A total of 33 articles involving 5677 cases and 5257 controls were included in the analysis. Significant associations were observed for VDR TaqI rs731236 polymorphism in the dominant and recessive models and VDR BsmI rs1544410 polymorphism in the dominant and recessive models. For ADIPOQ T45G rs2241766, a significant association was found in the heterozygous model. The results did not reveal any significant associations for ADIPOQ G276T rs1501299. Conclusion: This meta-analysis suggests associations between specific gene polymorphisms (VDR and ADIPOQ) and PCOS susceptibility. Further research is needed to validate these findings and unravel the complex genetic factors contributing to PCOS, potentially leading to improved diagnostic and therapeutic strategies.

Association between Mir-499, Mir-27a, and Mir-146a polymorphisms and their susceptibility to recurrent spontaneous abortion; in silico analysis.

Recurrent spontaneous abortion (RSA) is defined as two or more pregnancy losses before 24 gestational weeks, accounting for 1-3% of fertile couples. A vast majority of single-nucleotide polymorphisms (SNPs) in some microRNA (miRNA) genes can change the miRNA-mRNA interaction and are associated with the risk of RSA. This study was designed to better elucidate the association between miR-27a, miR-499, and miR-146a polymorphisms and RSA risk. SNP genotyping of miR-27a (rs895819), miR-499 (rs3746444), and miR-146a (rs2910164) was performed using polymerase chain reaction (PCR)-restriction fragment length polymorphism and tetra amplification-refractory mutation system PCR in 98 patients with RSA and 105 healthy subjects. Our results showed that the miR-499 rs3746444 and miR-27a rs895819 polymorphisms were significantly associated with RSA risk, whereas no significant differences were observed between the rs2910164 polymorphism and RSA susceptibility. We proposed that the miR-499 rs3746444 and miR-27a rs895819 polymorphisms were correlated with RSA in our population, but the miR-146a rs2910164 variant was not associated with the risk of RSA.

Association of TLR4 polymorphisms (Asp299Gly and Thr399Ile) with sepsis: a meta-analysis and trial sequence analysis.

Several investigations have been carried out to explore the genetic association of TLR4 codon variants, specifically Asp299Gly and Thr399Ile, and susceptibility to sepsis, but the results have been contradictory. The present study aimed to conduct a meta-analysis to draw a definitive conclusion regarding the role of TLR4 genetic variants (Asp299Gly and Thr399Ile) in sepsis. A thorough literature search was conducted using the PubMed, Scopus, and Science Direct databases. The inclusion and exclusion criteria were established to ensure the accuracy of the data. The Comprehensive Meta-Analysis Software v4 was utilized to perform the meta-analysis and related analyses. A total of 13 studies were analyzed, including 2328 sepsis cases and 2495 healthy controls for the TLR4 Asp299Gly variant. Eight studies provided genotype data for the rs4986791 polymorphism. The Asp299Gly variant showed a marginal protective effect in the allele (p = 0.08, odds ratio = 0.71) and dominant (p = 0.09, odds ratio = 0.71) genetic models, although it was not statistically significant. The trial sequential analysis indicated that further case-control studies are necessary to draw definitive conclusions about the TLR4 polymorphisms in sepsis. The TLR4 Asp299Gly variant may have a protective effect against sepsis. However, additional research with larger sample sizes across diverse populations is required to validate this finding.

Common variants of vitamin D receptor gene polymorphisms and risk of gastric cancer: A meta-analysis.

While earlier studies have suggested that variations in the vitamin D receptor (VDR) gene could influence the susceptibility to gastric cancer (GC), the results have shown inconsistency. This meta-analysis aimed to examine the association of 5 common polymorphisms in VDR, including Taq1 rs731236 (T > C), FokI rs2228570 (C > T), Cdx2 rs11568820 (G > A), BsmI rs1544410 (G > A), and ApaI rs7975232 (G > T) with the risk of GC. A comprehensive search was carried out in PubMed, Web of Science, and Scopus to identify relevant studies published until January 2024. Odds ratios (ORs) with 95% confidence intervals (CIs) were utilized to assess the magnitude of associations. Nine studies, with 2837 participants (1215 GC cases and 1622 healthy controls), were eligible. The FokI rs2228570 polymorphism showed a significant correlation with heightened susceptibility to GC under the recessive model (OR = 1.52; 95% CI: 1.06-2.19) and homozygote comparison (TT vs CC; OR = 1.59; 95% CI: 1.09-2.31). Taq1 rs731236 was also linked to an elevated risk of GC under the same models (recessive OR = 1.65; 95% CI: 1.14-2.39; homozygote OR = 1.68; 95% CI: 1.11-2.54). In the sensitivity analysis, when studies not adhering to Hardy-Weinberg equilibrium were excluded, the relationship between FokI rs2228570 polymorphism and GC disappeared, while the association for Taq1 rs731236 remained consistent. No significant association was identified for BsmI rs1544410, ApaI rs7975232, and Cdx2 rs11568820. This study revealed that FokI rs2228570 and Taq1 rs731236 polymorphisms of VDR might be linked to the odds of GC.

Arterial stiffness and genetic polymorphism of some cytokines in normotensive patients with ankylosing spondylitis

Aim of the study was to identify the incidence of arterial stiffness in normotensive patients with ankylosing spondylitis (AS) in the Trans-Baikal region, to study polymorphism of genes for some cytokines and prognostic factors for increased arterial stiffness in this disease. Material and methods. We examined 100 patients with AS, natives of the Transbaikal region, HLA-В27 positive and 100 healthy controls, HLA-B27 negative; all included in the study were Caucasian. Arterial hypertension was an exclusion criterion. Determination of single nucleotide polymorphisms of the genes IL1B (‒31T/C, rs1143627), IL10 (‒592C/A, rs1800872), IL10 (‒819C/T, rs1800871), TNF (‒308G/A, rs1800629) was carried out in all patients with AS and healthy individuals. 74 patients with AS and 40 patients in the control group underwent applanation tonometry using SphygmoCor (AtCor Medical, Australia). Results. Pulse wave velocity on the carotid-femoral segment in patients with AS was 6.5 [4.1; 11.7] m/s, in the control group – 5.2 [3.9; 7.0] m/s (p = 0.0001). In 18 patients with AS (24.32 %) it was more than the age norm, these patients made up the group with elevated arterial stiffness. In patients with AS, carriage of the homozygous AA genotype of the IL10 gene (rs1800872, ‒592C/A) was 2.18 times more common, the homozygous GG genotype of the TNF gene (rs1800629, ‒308G/A) was 1.23 times more common, and the heterozygous ST genotype of the IL10 gene (rs1800871, ‒819C/T) was 1.5 times more common than in the control group. Prognostic factors for increased arterial stiffness in patients with AS were carriage of the IL10 rs1800871 polymorphism, age, and the radiological stage of changes in the sacroiliac joints. Conclusions. Increased arterial stiffness was detected in 24.3 % of normotensive patients with AS. The CT genotype of the IL10 gene (rs1800871, ‒819C/T), AA genotype of the of the IL10 gene (rs1800872, ‒592C/A), the G allele and the GG genotype of the TNF gene (rs1800629, позиция ‒308G/A) are associated with the development of AS in Caucasians. Multivariate regression analysis identified clinical and genetic factors that predict an increase in arterial stiffness in patients with AS, natives of the Trans-Baikal Territory.

Association of the vitamin D metabolism gene polymorphism with the severity of coronary lesions assessed by SYNTAX score

This study aimed to determine the association of vitamin D serum blood levels and vitamin D gene polymorphism with the severity of coronary lesions in patients with stable coronary artery disease (CAD). Material and methods. 260 patients with stable CAD (average age was 58 years) were examined in the presented research. All patients were divided into two groups according to the SYNTAX score: low-risk patients with SYNTAX score ≤ 31 (n = 224) and high-risk patients with SYNTAX score &gt; 31 (n = 36). For enzyme-linked immunosorbent assay and genetic analysis, peripheral blood was collected from the cubital vein into vacuum tubes containing coagulation activator and K3-EDTA, respectively. Serum blood level of 25-hydroxyvitamin D (DiaSource Diagnostics, Belgium) and 1,25-dihydroxyvitamin D (Immunodiagnostic Systems, Great Britain) were determined by enzyme-linked immunosorbent assay according to the manufacturers’ protocols. Genomic DNA was isolated by phenol-chloroform extraction method from whole blood. The quality and quantity of isolated DNA were assessed using NanoDrop spectrophotometer (Thermo Fisher Scientific, USA). Five polymorphic variants in the VDR (rs2228570 and rs73123) and GC (rs7041, rs1155563 and rs2298849) genes were selected for analysis. Genotyping was performed by real-time PCR in a 96-well plate with fluorescently labeled TaqMan probes. The quality of PCR was controlled by repeated genotyping of 10 % of the analyzed samples. Results. We found no statistically significant differences in serum blood level of the studied markers in patients from low-risk and high-risk groups. One polymorphic variant in the GC gene associated with the multiple coronary lesions (rs2298849) (odds ratio 2.26, 95 % confidence interval 1.28–3.99, p = 0.006) according to an additive inheritance model was identified. In addition, we determined the association between low serum blood level of 1,25-dihydroxyvitamin D in patients with CAD with multiple lesions of the coronary vascular system with A/A – A/G genotypes of the rs2228570 polymorphism in the VDR gene, A/A genotype of the rs7041 polymorphism and A/A genotype of the rs2298849 polymorphism in the GC gene. Conclusions. Allelic variants in the vitamin D metabolism genes are associated with the degree of coronary artery lesions assessed by the SYNTAX score in patients with stable CAD. Also, serum blood level of the active form of vitamin D (1,25-dihydroxyvitamin D) is less in carriers of homozygous genotypes for the major alleles of the VDR and GC genes.