Dataset Information

Association of Interleukin-1 Beta and Interleukin-1 Receptor Antagonist Gene Polymorphisms and Plasma Levels with Diabetic Nephropathy.

ABSTRACT:

Objective

We investigated the relationships between interleukin- (IL-) 1β and IL-1 receptor antagonist (IL-1Ra) gene polymorphism and plasma levels in patients with diabetic nephropathy (DN).

Methods

The genotype and allele frequency distribution of IL-1β and IL-1Ra in 61 patients with DN and 48 healthy controls (HCs) were determined by kompetitive allele-specific PCR (KASP), and the plasma concentrations of IL-1β and IL-1Ra in DN patients and HCs were measured by enzyme-linked immunosorbent assays (ELISA).

Results

Significant differences were detected in the distribution of IL-1β (-511C/T) genotype and allele frequencies between the DN and HC groups (P < 0.05), with the T genotype being more frequent in DN patients than HCs (OR = 2.84, 95% CI: 1.489-5.416). The IL-1β (+3953C/T) and IL-1Ra (+8006C/T) genotypes and allele frequencies were not significantly different between the two groups (P > 0.05). The plasma IL-1β level was significantly higher (P < 0.01), while the plasma IL-1Ra concentration was significantly lower in the DN group than the HC group (P < 0.05). Furthermore, the plasma IL-1β level was significantly different between IL-1β (-511C/T) locus variants (P < 0.05).

Conclusion

The IL-1β (-511C/T) gene polymorphism was significantly associated with DN risk in the population of northern Guangxi, China, and the T allele maybe responsible for genetic susceptibility to DN.

SUBMITTER: Liao X

PROVIDER: S-EPMC9159863 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Association of Interleukin-1 Beta and Interleukin-1 Receptor Antagonist Gene Polymorphisms and Plasma Levels with Diabetic Nephropathy.

Liao Xueling X Xiao Yanan Y Elbelt Ulf U Weylandt Karsten H KH Li Kanghui K Deng Jie J Zeng Ning N Xue Chao C

BioMed research international 20220525

<h4>Objective</h4>We investigated the relationships between interleukin- (IL-) 1<i>β</i> and IL-1 receptor antagonist (IL-1Ra) gene polymorphism and plasma levels in patients with diabetic nephropathy (DN).<h4>Methods</h4>The genotype and allele frequency distribution of IL-1<i>β</i> and IL-1Ra in 61 patients with DN and 48 healthy controls (HCs) were determined by kompetitive allele-specific PCR (KASP), and the plasma concentrations of IL-1<i>β</i> and IL-1Ra in DN patients and HCs were measure ...[more]

PMID: 35663044

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Project description:ObjectivePlasma interleukin-1 beta may influence sepsis mortality, yet recombinant human interleukin-1 receptor antagonist did not reduce mortality in randomized trials. We tested for heterogeneity in the treatment effect of recombinant human interleukin-1 receptor antagonist by baseline plasma interleukin-1 beta or interleukin-1 receptor antagonist concentration.DesignRetrospective subgroup analysis of randomized controlled trial.SettingMulticenter North American and European clinical trial.PatientsFive hundred twenty-nine subjects with sepsis and hypotension or hypoperfusion, representing 59% of the original trial population.InterventionsRandom assignment of placebo or recombinant human interleukin-1 receptor antagonist × 72 hours.Measurements and main resultsWe measured prerandomization plasma interleukin-1 beta and interleukin-1 receptor antagonist and tested for statistical interaction between recombinant human interleukin-1 receptor antagonist treatment and baseline plasma interleukin-1 receptor antagonist or interleukin-1 beta concentration on 28-day mortality. There was significant heterogeneity in the effect of recombinant human interleukin-1 receptor antagonist treatment by plasma interleukin-1 receptor antagonist concentration whether plasma interleukin-1 receptor antagonist was divided into deciles (interaction p = 0.046) or dichotomized (interaction p = 0.028). Interaction remained present across different predicted mortality levels. Among subjects with baseline plasma interleukin-1 receptor antagonist above 2,071 pg/mL (n = 283), recombinant human interleukin-1 receptor antagonist therapy reduced adjusted mortality from 45.4% to 34.3% (adjusted risk difference, -0.12; 95% CI, -0.23 to -0.01), p = 0.044. Mortality in subjects with plasma interleukin-1 receptor antagonist below 2,071 pg/mL was not reduced by recombinant human interleukin-1 receptor antagonist (adjusted risk difference, +0.07; 95% CI, -0.04 to +0.17), p = 0.230. Interaction between plasma interleukin-1 beta concentration and recombinant human interleukin-1 receptor antagonist treatment was not statistically significant.ConclusionsWe report a heterogeneous effect of recombinant human interleukin-1 receptor antagonist on 28-day sepsis mortality that is potentially predictable by plasma interleukin-1 receptor antagonist in one trial. A precision clinical trial of recombinant human interleukin-1 receptor antagonist targeted to septic patients with high plasma interleukin-1 receptor antagonist may be worthy of consideration.

Project description:BackgroundAsthma is a complex polygenic disease in which gene-environment interactions are important. A number of studies have investigated the polymorphism of IL-1β -511C/T and IL-1RA genes in relation to asthma susceptibility in different populations. However, the results of individual studies have been inconsistent. Accordingly, we conducted a comprehensive meta-analysis to investigate the association between the IL-1β -511C/T and IL-1RA polymorphism and asthma risk.MethodsData were collected from the following electronic databases: Pub Med, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), ISI Web of Knowledge, and Google Scholar Search databases with the last report up to July 2013. Finally, 15 studies were included in our meta-analysis. We summarized the data on the association between IL-1β -511C/T and IL-1RA polymorphism and risk of asthma in the overall population and performed subgroup analyses by ethnicity, mean of age, and source of controls. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the associations between IL-1β -511C/T and IL-1RA polymorphism and asthma risk. Statistical analysis was performed with Review Manager 5.1.ResultsA total of 15 case-control studies were included in the meta-analysis of IL-1β -511C/T (1,385 cases and 1,964 controls) and IL-1RA (2,800 cases and 6,359 controls) genotypes. No association was found between IL-1β -511C/T polymorphism and asthma risk (dominant model: OR = 1.11, 95% CI: 0.99-1.25, P = 0.07, P Heterogeneity = 0.06; recessive model: OR = 1.04, 95% CI: 0.91-1.20, P = 0.55, P Heterogeneity = 0.11). Subgroup analysis based on ethnicity (Asian and Caucasian), source of controls (population-based controls and hospital-based controls), and mean of age (adulthood and childhood) did not present any significant association. The overall results showed that the IL-1RA polymorphism was related to an increased risk of asthma (homozygote model: OR = 1.32, 95% CI: 1.12-1.56, P = 0.0009, P Heterogeneity = 0.87; recessive model: OR = 1.39, 95% CI: 1.18-1.63, P = 0.0001, P Heterogeneity = 0.82). Similar results were found in the subgroup analyses by ethnicity, mean of age, and source of controls. Sensitivity analysis did not perturb the results.ConclusionsThis meta-analysis provided strong evidence that the IL-1RA polymorphism was a risk factor of asthma, especially in Caucasian populations. However, no association was found for IL-1β -511C/T genotype carriers. Larger scale studies are needed for confirmation.

Dataset Information

Association of Interleukin-1 Beta and Interleukin-1 Receptor Antagonist Gene Polymorphisms and Plasma Levels with Diabetic Nephropathy.

Objective

Methods

Results

Conclusion

Publications

Association of Interleukin-1 Beta and Interleukin-1 Receptor Antagonist Gene Polymorphisms and Plasma Levels with Diabetic Nephropathy.

Similar Datasets

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