Interleukin-6 Rs1800795 Polymorphism Research Articles

Genetic Variant rs1800795 (G>C) in the Interleukin 6 (IL6) Gene and Susceptibility to Coronary Artery Diseases, Type 2 Diabetes, Acute Pancreatitis, Rheumatoid Arthritis, and Bronchial Asthma in Asians: A Comprehensive Meta-Analysis Based on 30154 Subjects

Numerous studies conducted globally have explored the possible connection between the IL6 gene variant rs1800795 (G>C) and the risk of several diseases. Nonetheless, the correlation specifically within the Asian population remains inconclusive. Hence, this extensive meta-analysis aims to establish a conclusive correlation between the rs1800795 variant and susceptibility to various diseases among Asians. Fifty eligible articles were chosen from Google Scholar, PubMed, Web of Science, and PMC based on specific inclusion criteria. Odds ratios alongside 95% confidence intervals (CI) were utilized. Additionally, subgroup analysis, publication bias, and sensitivity evaluation were conducted. The analysis, of 14,737 cases and 15,417 controls, showed a notable correlation between the rs1800795 (G>C) single-nucleotide polymorphism and the overall disease susceptibility to all models (p-value <2.5E-05). The ethnicity-specific stratified findings indicated that the C-allele of (C vs. G) model of −174G/C polymorphism expressively elevated the overall disease susceptibility in both East and South Asian populations. The disease-based stratified analyses suggested that the C variant of rs1800795 was related to coronary artery diseases and bronchial asthma (under all models), type 2 diabetes (CG vs. GG), acute pancreatitis (AP) (C vs. G; and CC vs. GG), rheumatoid arthritis (CC+CG vs. GG; CC vs. CG+GG; and C vs. G), and AP (C or CC vs. G or GG respectively). IL6 rs1800795 polymorphism is a highly significant disease risk factor in Asians and can potentially serve as a prognostic biomarker for future disease screening and evaluation.

Obesity is associated with IL-6 gene polymorphisms rs1800795 and rs1800796 but not SOCS3 rs4969170.

An imbalance of inflammatory factors can stimulate obesity by inducing chronic inflammation in adipose tissue. Interleukin-6 (IL-6) is a cytokine with both inflammatory and anti-inflammatory functions. Suppressor of cytokine signaling 3 (SOCS3) acts as an inhibitor for a number of cytokine signals. The IL-6 and SOCS3 genes are known to be involved in lipid and energy metabolism, although it is unclear how these genes relate to obesity. The aim of this study is to determine whether the obesity risk is associated with the IL-6 (rs1800795, rs1800796) and SOCS3 (rs4969170) gene polymorphisms. Based on their body mass index (BMI) scores, 185 people were determined, of whom 90 were from the control group and 95 were obese. Anthropometric measurements and biochemical parameters of the study subjects were documented during the examination. Genomic DNA isolation was performed from the blood samples of all participants. IL-6 (rs1800795, rs1800796) and SOCS3 (rs4969170) polymorphisms were detected by real-time quantitative polymerase chain reaction (qRT-PCR) from genomic DNA samples. The IL-6 rs1800795 and rs1800796 variants showed a significant difference between the control and obese groups (p = 0.027; p = 0.013). The SOCS3 rs4969170 variation did not substantially differ between the control and obese groups (p = 0.825). In our study, IL-6 rs1800795(G/C) and rs1800796(G/C) polymorphisms appeared to be a risk factor for obesity. The C allele was associated with the obesity phenotypes. However, the SOCS3 rs4969170 (A/G) polymorphism was not linked to an increased risk of obesity. IL-6 polymorphisms may be new targets for obesity treatment.

Association between Interleukin-6 rs1800795 Polymorphism and Serum Interleukin-6 Levels and Full-Term Neonatal Sepsis

Abstract Objective Cytokines are involved in the pathogenesis of sepsis. Association between IL-6 rs1800795 G/C polymorphism and the risks of sepsis is controversial. The aim of this study was to investigate the association of IL-6 rs1800795 G/C gene polymorphism with full-term neonatal sepsis and to determine its effect on the serum IL6 levels in these infants by a prospective study. Methods The study included 200 full-term neonates from January 2019 to December 2020: 100 with sepsis (sepsis group), 47 with culture proven sepsis, and 53 with clinical sepsis, and 100 without infection (control group). The concentrations of IL-6 in serum were determined using enzyme-linked immunosorbent assay (ELISA). The polymorphisms of IL-6 rs1800795 G/C were analyzed to compare the genotypic and allelic frequencies in the groups by using the first-generation sequencing (Sanger sequencing). The association was studied between IL-6 rs1800795 G/C polymorphisms and serum IL-6 levels, and neonatal sepsis. The relationships between IL-6 rs1800795G/C polymorphisms and sepsis and serum IL-6 levels were separately analyzed by logistic regression and analysis of variance. Results There were no significant differences in genotypic frequencies and allelic frequencies of IL-6 rs1800795(G/C) in the groups (p >0.05). There were no relations between IL-6 rs1800795G/C polymorphisms and sepsis and serum IL-6 levels by statistical analysis (p >0.05). Conclusion IL-6rs1800795G/C may not be genetic risk factors for full-term neonates; There was no association between serum IL-6 levels and IL-6 rs1800795G/C polymorphisms.

Erratum: Association between Interleukin-6 rs1800795 Polymorphism and Serum Interleukin-6 Levels and Full-Term Neonatal Sepsis

Erratum: Association between Interleukin-6 rs1800795 Polymorphism and Serum Interleukin-6 Levels and Full-Term Neonatal Sepsis

IL-6 gene rs1800795 polymorphism and diabetes mellitus: a comprehensive analysis involving 42,150 participants from a meta-analysis

BackgroundOver the past two decades, several studies have focused on the association between a common polymorphism (rs1800795) from interleukin-6 (IL-6) gene and Diabetes Mellitus (DM) risk. However, the results remain ambiguous and indefinite.MethodsA comprehensive analysis was performed to explore this relationship. A search was conducted in the PubMed, Embase, Chinese (CNKI and Wanfang), and GWAS Catalog databases, covering all publications until February 10, 2022. Odds ratios (OR) with 95% confidence intervals (CI) were used to evaluate the strength of the association. Publication bias was assessed using both Begg and Egger tests.ResultsOverall, 34 case–control studies with 7257 T2DM patients and 15,598 controls, and 12 case–control studies (10,264 T1DM patients and 9031 health controls) were included in the analysis. A significantly lower association was observed between the rs1800795 polymorphism and T2DM risk in Asians, mixed population, and hospital-based (HB) subgroups (C-allele vs. G-allele: OR = 0.76, 95% CI 0.58–0.99, P = 0.039 for Asians; CG vs. GG: OR = 0.74, 95% CI 0.58–0.94, P = 0.014 for mixed population; CC vs. GG: OR = 0.61, 95% CI 0.41–0.90, P = 0.014 for HB). However, increased associations were found from total, mixed population, and HB subgroups between rs1800795 polymorphism and T1DM susceptibility (CG vs. GG: OR = 1.32, 95% CI 1.01–1.74, P = 0.043 for total population, CC vs. GG: OR = 2.45, 95% CI 1.18–5.07, P = 0.016 for mixed individuals; C-allele vs. G-allele: OR = 1.29, 95% CI 1.07–1.56, P = 0.0009 for HB subgroup).ConclusionsIn summary, there is definite evidence to confirm that IL-6 rs1800795 polymorphism is associated with susceptibility to decreased T2DM and increased T1DM.

The Influence of Treatment with PCSK9 Inhibitors and Variants in the CRP (rs1800947), TNFA (rs1800629), and IL6 (rs1800795) Genes on the Corresponding Inflammatory Markers in Patients with Very High Lipoprotein(a) Levels.

Chronic inflammation contributes significantly to the development and progression of atherosclerosis. However, the factors that lead to an inflammatory imbalance towards a proinflammatory state are not yet fully understood. The CRP rs1800947, TNFA rs1800629, and IL6 rs1800795 polymorphisms may play a role in the pathogenesis of atherosclerosis and were therefore selected to investigate the influence of genetic variability on the corresponding plasma levels after treatment with a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor. A group of 69 patients with stable coronary artery disease after myocardial infarction before the age of 50 years and very high lipoprotein(a) levels were enrolled in the study. All patients received a PCSK9 inhibitor (evolocumab or alirocumab). Genotyping was performed using TaqMan assays (CRP rs1800947, TNFA rs1800629, and IL6 rs1800795). Consistent with previous studies, no significant change in levels of inflammatory biomarkers was observed after 6 months of treatment with PCSK9 inhibitors. We also did not detect any significant association between single nucleotide polymorphisms CRP rs1800947, TNFA rs1800629, and IL6 rs1800795 and plasma levels of high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor-α (TNF-α), or interleukin 6 (IL6), respectively, at enrollment. However, the difference in IL6 levels after treatment with PCSK9 inhibitors was statistically significant (p = 0.050) in patients with IL6-74CC genotype, indicating the possible role of the IL6 rs1800795 polymorphism in modulating inflammation.

The Determination of IL-6 rs1800795 Polymorphism Distribution in Turkish National Cross-Country Skiing Athletes Sub-groups Created Referring to the 1km CCSTAs

Objective: Interleukin-6 (IL-6) is an effective and functional protein with a cytokine structure. IL-6 is effective in the immune system like a pro/anti-inflammatory response, and muscle tissue hypertrophy and repair. Our study aimed to investigate the IL-6 rs1800795 polymorphism distribution in Turkish National Cross-Country Skiing Athletes and to determine the advantageous genotype for endurance performance. 
 Methods: 34 athletes within 3 groups; General (Group-1), Women (Group-2), and Men (Group-3) were enrolled to the study. Also each groups were divided into sub-groups according to their “1-kilometer cross-country average skiing-times (1 km-CCSTAs)”. Blood samples were used for DNA isolation and genotyping were completed by real time- PCR. 
 Results: The groups' 1 km-CCSTAs were 188.7 ± 22.4, 212.3 ± 17.8, and 177.4 ± 14.1 seconds, respectively. We detected the genotypes as 17 GG (50%) and 17 GC (50%) in Group-1; 5 GG (45%) and 6 GC (55%) in Group-2; 12 GG (52%) and 11 GC (48%) in Group- 3. We detected no CC genotype in groups. Chi-square Fisher’s test was used for statistical analysis. 
 Conclusion: An increased GC genotype ratio was detected in the faster sub-groups of each group compared to the slower sub-groups. But we obtained the significant genotype distribution only in Group-3 (p

Associations between Certain Polymorphisms in Proinflammatory Cytokines and Predisposition of Alzheimer’s Disease: A Meta-Analysis

Background: Functional gene polymorphisms of proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-18 (IL-18) may contribute to the onset and development of Alzheimer’s disease (AD), but the relationships between these polymorphisms and predisposition of AD remain controversial. Objectives: This meta-analysis was conducted to more robustly assess relationships between TNF-α/IL-6/IL-8/IL-18 polymorphisms and predisposition of AD by pooling the findings of relevant studies. Methods: A comprehensive literature searching was performed in PubMed, Embase, Web of Science, Wanfang, and CNKI databases, and 63 studies were found to be eligible for quantitative analyses. Results: The pooled meta-analysis results showed that genotypic frequencies of TNF-α rs1800629, IL-6 rs1800795, IL-8 rs4073, and IL-18 rs187238 polymorphisms among AD cases and controls of Asian ethnicity differed significantly. But, we did not observe such genotypic frequencies differences in Caucasians. Conclusions: This meta-analysis suggests that TNF-α rs1800629, IL-6 rs1800795, IL-8 rs4073, and IL-18 rs187238 polymorphisms may affect predisposition of AD in Asians, but not in Caucasians.

Interleukin 6 (rs1800795) and pentraxin 3 (rs2305619) polymorphisms-association with inflammation and all-cause mortality in end-stage-renal disease patients on dialysis

Chronic inflammation plays an important role in the progression and outcome of chronic kidney disease (CKD). The circulating levels of the inflammatory biomarkers interleukin 6 (IL6) and pentraxin 3 (PTX3) are enhanced in CKD patients, and are associated with the progression of the disease and with higher risk for cardiovascular events, the major cause of death in CKD patients. Our aim was to study how specific polymorphisms of IL6 and PTX3 encoding genes affect the inflammatory response and outcome of end-stage renal disease (ESRD) patients on dialysis. Methodology included the analysis of two single nucleotide polymorphisms (SNP), namely the IL6 (rs1800795) polymorphism in the promoter region (-174G > C), and the PTX3 (rs2305619) polymorphism in the intron 1 (+ 281A > G), which were analyzed in ESRD patients on dialysis and in a group of heathy individuals. The allelic frequencies, genotype distribution and their association with circulating levels of the inflammatory markers C-reactive protein (CRP), IL6, growth differentiation factor 15 (GDF15) and PTX3, were determined in ESRD patients. Events of death were recorded along one year, to assess the association of the studied SNPs with all-cause mortality and the inflammatory biomarkers, in ESRD patients. Results showed that the allelic frequencies and genotype distribution for IL6 and PTX3 SNPs in the control group and ESRD patients were similar and in agreement with other European reports. For the IL6 polymorphism, we found a trend towards higher levels of high-sensitivity (hs) CRP, IL6 and PTX3 in the homozygous genotypes; the CC genotype also showed the highest levels of GDF15. The mortality rate after the 1-year follow-up was 10.4%. The CC genotype (IL6 SNP) was associated to a higher risk of mortality and deceased patients carrying this genotype also showed the highest levels of hsCRP. Regarding the studied PTX3 SNP, the AA genotype was linked to an enhanced inflammatory response, showing the highest values of hsCRP and IL6. Nevertheless, this genotype had no significant impact on the mortality rate. In conclusion, both studied SNPs seem to modulate the inflammatory response in ESRD and may, therefore, be determinant on disease progression and patients’ outcome. Our data also highlights the importance of research on genetic variants that, although less frequent, may have significant biological value.

Gene polymorphisms of pro-inflammatory cytokines may affect the risk of Graves' disease: a meta-analysis.

Gene polymorphisms of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1) and interleukin-6 (IL-6) may influence the risk of Graves' disease, but the results of so far published studies remain inconclusive. Therefore, the authors conducted this meta-analysis to assess relationships between TNF-α/IL-1/IL-6 polymorphisms and the risk of Graves' disease by pooling the findings of all relevant studies. A comprehensive literature searching of Pubmed, Embase, Web of Science and CNKI was conducted by the authors, and twenty-eight studies were found to be eligible for pooled analyses. The pooled meta-analyses results showed that genotypic frequencies of TNF-α rs1800629, IL-1A rs1800587, IL-6 rs1800795 and IL-6 rs1800796 polymorphisms among patients with Graves' disease and control subjects differed significantly. Moreover, we found that genotypic frequencies of TNF-α rs1800629 and IL-6 rs1800795 polymorphisms among patients with Graves' disease and control subjects in Caucasians differed significantly, and genotypic frequencies of IL-1A rs1800587, IL-1B rs16944, IL-6 rs1800795 and IL-6 rs1800796 polymorphisms among patients with Graves' disease and control subjects in Asians also differed significantly. Nevertheless, we did not detect such genotypic frequencies differences for TNF-α rs361525 and IL-1B rs1143627 polymorphisms. This meta-analysis suggests that TNF-α rs1800629, IL-1A rs1800587, IL-6 rs1800795 and IL-6 rs1800796 polymorphisms may influence the risk of Graves' disease in overall population. Moreover, TNF-α rs1800629 and IL-6 rs1800795 polymorphisms may influence the risk of Graves' disease in Caucasians, while IL-1A rs1800587, IL-1B rs16944, IL-6 rs1800795 and IL-6 rs1800796 polymorphisms may influence the risk of Graves' disease in Asians.

IL-10, IL-18 Gene Polymorphisms Might Influence Predisposition to Coronary Artery Disease in East Asians: A Meta-Analysis

ABSTRACT The results of already published studies regarding relationship between interleukin-10 (IL-10), interleukin-18 (IL-18) polymorphisms and predisposition to coronary artery disease (CAD) were still controversial. So the authors designed this meta-analysis to more precisely estimate relationship between IL-10, IL-18 polymorphisms and CAD by pooling the results of already published studies. The authors searched Pubmed, Embase, Web of Science and CNKI for already published studies. The authors used Review Manager to pool the results of already published studies. Thirty-four studies were pooled analyzed in this meta-analysis. The pooled meta-analyses results showed that IL-18 rs187238, IL-18 rs1946518 and IL-18 rs1946519 polymorphisms were all significantly associated with predisposition to CAD in the general population. We also detected similar significant results for IL-10 rs1800871, IL-10 rs1800896, IL-18 rs187238 and IL-18 rs1946518 polymorphisms in East Asians in further subgroup analyses. In conclusion, this meta-analysis suggested that IL-10 rs1800871, IL-10 rs1800896, IL-18 rs187238 and IL-18 rs1946518 polymorphisms might influence predisposition to CAD in East Asians.

INTERACTIONS AMONG INTERLEUKIN-6, C-REACTIVE PROTEIN AND INTERLEUKIN-6 (-174) G/C POLYMORPHISM IN THE PATHOGENESIS OF CROHN'S DISEASE AND ULCERATIVE COLITIS.

SUMMARYInflammatory bowel diseases are multifactorial disorders the clinical manifestation of which depends on the interaction among immune response, genetic and environmental factors. There is growing evidence that cytokines and gene polymorphisms have an important role in disease pathogenesis in various populations although molecular mechanism of their signaling and interactions is not fully understood yet. The present study aimed at exploring the effects of interleukin-6, C-reactive protein and interleukin-6 rs1800795 polymorphism on the development of Crohn’s disease, ulcerative colitis and inflammatory bowel diseases overall and at determining differences between inflammatory bowel disease patients and healthy controls. A total of 132 inflammatory bowel disease patients and 71 healthy blood donors were investigated. In order to assess the clinical relevance of interleukin-6 and C-reactive protein serum concentration and interleukin-6 rs1800795 single nucleotide polymorphism in patients with Crohn’s disease and ulcerative colitis, we performed a cross-sectional, case-control study. Quantitative assessment of serum interleukin-6 and C-reactive protein was performed with solid-phase, enzyme-labeled, chemiluminescent sequential immunometric and immunoturbidimetric assay, respectively. A real-time fluorescence resonance energy transfer-based method on a LightCyclerTM PCR 1.2 was used for genotyping of IL-6 rs1800795 polymorphism. Both interleukin-6 and C-reactive protein serum levels were elevated in Crohn’s disease and ulcerative colitis patients. Positive correlations were observed between C-reactive protein and interleukin-6 serum concentration and ulcerative colitis activity index as measured by modified Truelove-Witt’s severity index scale. C-reactive protein serum level was higher in Crohn’s disease patients without intestinal resection than in Crohn’s disease patients with prior intestinal resection. In ulcerative colitis patients, interleukin-6 and C-reactive protein serum levels were statistically significantly higher in CC interleukin-6 genotype in comparison to GG+GC genotype. Analysis of the promoter region of the interleukin-6 rs1800795 gene polymorphism showed no statistically significant difference in allele frequency either between inflammatory bowel disease patients and healthy controls or between the two inflammatory bowel disease phenotypes and healthy controls. Associations presented in this study give a potentially important insight into the role of interleukin-6 and C-reactive protein signaling and interleukin-6 polymorphism in the pathogenesis of Crohn’s disease and ulcerative colitis disease.

Associations of polymorphisms in IL-6 and IL-18 with tuberculosis: Evidence from a meta-analysis

BackgroundAssociations between polymorphisms in interleukin-6 (IL-6)/interleukin-18 (IL-18) and tuberculosis (TB) were already reported by many publications. The aim of this meta-analysis was to better clarify associations between polymorphisms in IL-6/IL-18 and TB by combing the results of all relevant publications. MethodsEligible publications were searched from Pubmed, Embase, WOS and CNKI. We used Review Manager to combine the results of individual studies. ResultsTwenty-five studies were included in this study. IL-6 rs1800795 (dominant comparison: OR 1.43, 95% CI 1.23–1.67; recessive comparison: OR 0.48, 95% CI 0.35–0.65; allele comparison: OR 1.43, 95% CI 1.27–1.62), IL-18 rs1946518 (dominant comparison: OR 1.19, 95% CI 1.04–1.35; recessive comparison: OR 0.82, 95% CI 0.71–0.96; allele comparison: OR 1.14, 95% CI 1.05–1.24) and IL-18 rs187238 (dominant comparison: OR 1.35, 95% CI 1.15–1.58; allele comparison: OR 1.31, 95% CI 1.14–1.50) polymorphisms were all significantly associated with TB in the total population. Subgroup analyses showed that positive findings for rs1946518, rs187238 and rs1800795 polymorphisms were mainly driven by the Asians. ConclusionsCollectively, this meta-analysis proved that IL-6 rs1800795, IL-18 rs1946518 and IL-18 rs187238 polymorphisms may confer susceptibility to TB, especially for Asians.

Associations of six common functional polymorphisms in interleukins with tuberculosis: evidence from a meta-analysis

Associations of polymorphisms in interleukin-6 (IL-6), IL-8 and IL-10 with tuberculosis (TB) susceptibility were already reported by many publications. The aim of this meta-analysis was to more precisely clarify associations between polymorphisms in IL-6/IL-8/IL-10 and TB by combing the results of all relevant publications. Eligible publications were searched from PubMed, Embase, Web of Science and CNKI. We used Review Manager to combine the results of individual studies. A total of 47 publications were included in this study. IL-6 rs1800795 (1750 cases and 2335 controls, dominant, recessive and allele comparisons), IL-8 rs4073 (1125 cases and 1188 controls, dominant, recessive and allele comparisons), IL-10 rs1800871 (5528 cases and 7671 controls, dominant, recessive and allele comparisons), IL-10 rs1800872 (5269 cases and 7013 controls, dominant and allele comparisons) and IL-10 rs1800896 (7564 cases and 8952 controls, recessive comparison) polymorphisms were all significantly associated with TB in overall combined analyses. In subgroup analyses, we found that the positive results were mainly driven by the pulmonary tuberculosis and Asian subgroups. Collectively, this meta-analysis proved that IL-6 rs1800795, IL-8 rs4073, IL-10 rs1800871, IL-10 rs1800872 and IL-10 rs1800896 may confer susceptibility to TB.

A meta-analysis on associations of IL-6 and IL-10 polymorphisms with susceptibility to ischemic stroke

BackgroundSome previous studies already explored associations of interleukin-6 (IL-6) and interleukin-10 (IL-10) polymorphisms with ischemic stroke (IS). However, the results were conflicting. In this meta-analysis, we aimed to better analyze the relationship between IL-6/IL-10 polymorphisms and IS in a larger pooled population. MethodsWe performed a systematic search of PubMed, Web of Science, Embase and CNKI. We calculated pooled odds ratios (ORs) and 95% confidence intervals (CIs) to estimate associations between IL-6/IL-10 polymorphisms and IS. ResultsTotally 37 studies were included for analyses. A significant association with IS was observed for IL-10 rs1800896 polymorphism in AA versus GG + GA (recessive model, p = .001, OR = 1.42, 95%CI 1.15–1.75) in overall population. Further subgroup analyses showed that IL-6 rs1800795 was significantly associated with IS in Asians in GG versus GC + CC (dominant model, p = .0005, OR = 0.74, 95%CI 0.62–0.88), CC versus GG + GC (recessive model, p = .003, OR = 1.61, 95%CI 1.17–2.21) and G versus C (allele model, p = .01, OR = 0.74, 95%CI 0.58–0.93), whereas IL-10 rs1800896 polymorphism was significantly associated with cerebral infarction (CI) in GG versus GA + AA (dominant model, p = .02, OR = 2.04, 95%CI 1.14–3.64), GA versus GG + AA (overdominant model, p = .03, OR = 0.50, 95%CI 0.27–0.93) and G versus A (allele model, p = .01, OR = 1.92, 95%CI 1.16–3.17). ConclusionsOur findings indicated that IL-6 rs1800795 polymorphism was significantly associated with individual susceptibility to IS in Asians, but not in Caucasians. In addition, IL-10 rs1800896 polymorphism was also significantly associated with individual susceptibility to IS, especially for CI.

The Association of Catechol-O-Methyl-Transferase and Interleukin 6 Gene Polymorphisms with Posttraumatic Stress Disorder.

Posttraumatic stress disorder (PTSD) is a disorder that occurs in some people who have experienced a severe traumatic event. Several genetic studies suggest that gene encoding proteins of catechol-O-methyl-transferase (COMT) may be relevant for the pathogenesis of PTSD. Some researchers suggested that the elevation of interleukin-6 (IL6) correlates with major depression and PTSD. The aim of this study was to investigate whether the single nucleotide polymorphisms COMT rs4680 (Val158Met) and IL6 rs1800795 are associated with PTSD and contribute to the severity of PTSD symptoms. This study comprised 747 participants that experienced war between 1991 and 1999 in the South Eastern Europe conflicts. COMT rs4680 (Val158Met) and IL6 rs1800795 genotypes were determined in 719 participants (369 with and 350 without PTSD). The Mini International Neuropsychiatric Interview (M.I.N.I.), the Clinician Administrated PTSD Scale (CAPS) questionnaire and the Brief Symptom Inventory (BSI) were used for data collection. Regarding the COMT gene polymorphism, the results of the regression analyses for BSI total score were significant in the lifetime PTSD group in the dominant (P=0.031) and the additive allelic model (P=0.047). Regarding the IL6 gene, a significant difference was found for the recessive model predicting CAPS total score in the lifetime PTSD group (P=0.048), and indicated an association between the C allele and higher CAPS scores. n the allelic, genotypic and rezessive model, the results for BSI total score were significant in the lifetime PTSD group (P=0.033, P=0.028 and P=0.009), suggesting a correlation of the C allele with higher BSI scores. Although our nominally significant results did not withstand correction for multiple tests they may support a relevance of the COMT (Val158Met) and IL6 rs1800795 polymorphism for aspects of PTSD in war traumatized individuals.

Association between rs1800795 polymorphism in the interleukin-6 gene and the risk of polycystic ovary syndrome: A meta-analysis.

Objective:Several published articles have investigated the association between the −174 G/C (rs1800795) polymorphism in the interleukin-6 (IL-6) gene and the risk of polycystic ovary syndrome (PCOS). However, the results were inconsistent. In the present study, a meta-analysis was performed to resolve this inconsistency.Methods:Eligible studies reporting an association between the IL-6 rs1800795 polymorphism and PCOS susceptibility were included from PubMed, Embase, Web of Science, and the Cochrane Library up to December 1, 2017. The odds ratio (OR) with the 95% confidence interval (CI) was used to calculate the strength of the associations. Publication bias detection was conducted using Begg test. We used STATA 11.0 software to perform the statistical analyses.Results:Six articles detailing case-control studies were included, reporting a total of 512 cases and 606 controls. The meta-analysis results indicated that rs1800795 was associated with decreased PCOS susceptibility in the overall population under the allelic model (G vs. C, OR = 0.59, 95% CI: 0.41–0.85, P = .005), the homozygous model (GG vs. CC, OR = 0.45, 95% CI: 0.28–0.73, P = .001), heterozygous model (GG vs. CG, OR = 0.50, 95% CI: 0.26–0.95, P = .036), and the dominant model (GC + CC vs. GG, OR = 0.48, 95% CI: 0.26–0.89, P = .020). However, a threshold P value of .05 was found under the recessive model (CC vs. GG + CG, OR = 0.62, 95% CI: 0.39–1.00).Conclusions:This meta-analysis concluded that IL-6 rs1800795 polymorphism has a decreased association with PCOS risk among all populations studied. The results suggested that the IL-6 rs1800795 polymorphism is a protective factor for PCOS susceptibility. Given the limited ethnic groups and sample size, further studies are required to validate the association.

Association of the IL6 rs1800796, but not of the IL6 rs1800795, IL6R rs4845617 and rs2228145 polymorphisms with hip fracture in elderly Mexican women.

Polymorphisms in Interleukin-6 (IL6) and its receptor (IL6R) have been associated with bone mineral density. In this work, the G-174C and G-572C polymorphisms in IL6, G-208A, and Asp358Ala in IL6R were analyzed in Mexican women with hip fracture. Postmenopausal Mexican women (60 years or over) with hip fragility fracture (77.97 ± 8 years) and without hip fracture (70.5 ± 7.02 years) were genotyped by real-time PCR. The rs1800796 GG genotype was associated with low risk of fracture (p = 0.05), while GC genotype was associated with high risk of fracture [p = 0.047, OR 2.3 (95% CI 1.013-5.2)]. The AA genotype of the rs2228145 SNP (IL6R) was significantly different [p = 0.033, OR 1.94 (95% CI 1.01-3.75)], but when data were adjusted by age and body mass index, there were no differences (p = 0.9). Our results suggest that the IL6 rs1800796 SNP is a good marker for hip fracture risk in Mexican women.

Meta-analysis of the role of IL-6 rs1800795 polymorphism in the susceptibility to prostate cancer: Evidence based on 17 studies.

Playing critical roles in immune responses, interleukin-6 (IL-6) has been proposed to be involved in the development of multiple cancers, including prostate cancer. The rs1800795 polymorphism in the promoter of the gene IL-6 can affect the transcription and expression of the gene, becoming a common target in association studies on tumors. We therefore carried out this meta-analysis to further discuss the relationship of this polymorphism with the risk of prostate cancer.Relevant publications were retrieved from the electronic databases. The strength of the correlation between IL-6 rs1800795 polymorphism and prostate cancer risk was evaluated using pooled odds ratios (ORs) with their 95% confidence intervals (95% CIs). Q test was adopted to examine between-study heterogeneity, with P < 0.05 as significant level. Subgroup and meta-regression analyses were conducted to explore potential source of heterogeneity. Sensitivity analysis was implemented to test the statistical stability of the final results. In addition, funnel plot and Egger test were employed to inspect publication bias among included studies.A total of 13 132 cases and 15 282 controls were ultimately incorporated into the present study. Overall estimates revealed no significant relationship between IL-6 rs1800795 polymorphism and prostate cancer risk in total analysis, but a risk-increasing effect of the polymorphism was detected in African-American subgroup under CC versus GG and CC versus GG + GC contrasts (OR 3.43, 95% CI 1.01–11.71; OR 3.51, 95% CI 1.04–11.82) after subgroup analysis by ethnicity.IL-6 rs1800795 polymorphism may enhance the susceptibility to prostate cancer in African-American men.

Interactions between environmental factors and maternal–fetal genetic variations: strategies to elucidate risks of preterm birth

ContextPreterm birth (PTB) is a complex disease in which medical, social, cultural, and hereditary factors contribute to the pathogenesis of this adverse event. Interactions between genes and environmental factors may complicate our understanding of the relative influence of both effects on PTB. To overcome this, we combined data obtained from a cohort of newborns and their mothers with multiplex analysis of inflammatory-related genes and several environmental risk factors of PTB to describe the environmental–genetic influence on PTB. ObjectiveThe study aimed to investigate the association between maternal and fetal genetic variations in genes related to the inflammation pathway with PTB and to assess the interaction between environmental factors with these variations. Study designWe conducted a case–control study at the Pereira Rossell Hospital Center, Montevideo, Uruguay. The study included 143 mother–offspring dyads who delivered at preterm (gestational age<37 weeks) and 108 mother–offspring dyads who delivered at term. We used real-time PCR followed by a high-resolution melting analysis to simultaneously identify gene variations involved in inflammatory pathways in the context of environmental variables. The genes analyzed were: Toll-like receptor 4 (TLR4), Interleukin 6 (IL6), Interleukin 1 beta (IL1B) and Interleukin 12 receptor beta (IL12RB). ResultsWe detected a significant interaction between IL1B rs16944 polymorphism in maternal samples and IL6 rs1800795 polymorphism in newborns, emphasizing the role of the interaction of maternal and fetal genomes in PTB. In addition, smoke exposure and premature rupture of membranes (PROM) were significantly different between the premature group and controls. IL1B and IL6 polymorphisms in mothers were significantly associated with PTB when controlling for smoke exposure. TLR4 polymorphism and PROM were significantly associated with PTB when controlling for PROM, but only in the case of severe PTB. ConclusionsInteractions between maternal and fetal genomes may influence the timing of birth. By incorporating environmental data, we revealed genetic associations with PTB, a finding not found when we analyzed genetic data alone. Our results stress the importance of studying the effect of genotype interactions between mothers and children in the context of environmental factors because they substantially contribute to phenotype variability.