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Impact of IL-10 gene polymorphisms and its interaction with environment on susceptibility to systemic lupus erythematosus.

ABSTRACT: This study aims to explore the impact of interleukin (IL)-10 single nucleotide polymorphisms (SNPs) and its interaction with environment on the risk of systemic lupus erythematosus (SLE). Chi-square testing method was used to investigate whether the distributions for genotype of four SNPs were differed from Hardy-Weinberg equilibrium (HWE). Logistic regression was used to test the association between IL-10 SNPs and SLE risk. The best interaction combinations between IL-10 SNPs and environmental factors were assessed by generalized multifactor dimensionality reduction (GMDR). Both rs1800896-G and rs1800871-T alleles were associated with increased risk of SLE, the odds ratios (ORs) (95% confidence interval (CI)) for the two SNPs were 1.68 (1.25-2.09) and 1.47 (1.12-1.94), respectively. Then, we used the GMDR method to analyze the high-order interactions of four SNPs within IL-10 gene and environmental factors on SLE risk. We found a significant interaction combination (two-locus model with P?=?0.001) between rs1800896 and smoking, after adjusting for gender, age, body mass index (BMI), and alcohol drinking. We also used two-variable stratified analysis by logistic regression to analyze the synergistic effect between two variables (rs1800896 and smoking), which had significant significance in GMDR model. We found that current smokers with rs1800896-AG or GG genotype have the highest SLE risk, compared with never smokers with the rs1800896-AA genotype, OR (95% CI)?=?2.24 (1.52-3.58). The rs1800896-G and rs1800871-T alleles and interaction between rs1800896 and current smoking were all associated with increased risk of SLE.

SUBMITTER: Wang GH

PROVIDER: S-EPMC7453486 | biostudies-literature | 2020 Jan-Dec

REPOSITORIES: biostudies-literature

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Impact of IL-10 gene polymorphisms and its interaction with environment on susceptibility to systemic lupus erythematosus.

Wang Gui-Hong GH Wang Gui-Hong GH Zuo Ting T Zuo Zheng-Cai ZC

International journal of immunopathology and pharmacology 20200101

This study aims to explore the impact of interleukin (IL)-10 single nucleotide polymorphisms (SNPs) and its interaction with environment on the risk of systemic lupus erythematosus (SLE). Chi-square testing method was used to investigate whether the distributions for genotype of four SNPs were differed from Hardy-Weinberg equilibrium (HWE). Logistic regression was used to test the association between IL-10 SNPs and SLE risk. The best interaction combinations between IL-10 SNPs and environmental ...[more]

PMID: 32842808

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Project description:BackgroundA number of observational studies have been conducted to investigate the association of the IL-10 gene polymorphisms with systemic lupus erythematosus (SLE) susceptibility. However, their results are conflicting.MethodWe searched published case-control studies on the IL-10 polymorphisms and SLE in PubMed, EMBASE and Chinese Biomedical Literature Database. A meta-analysis was conducted using a fixed-effect or random-effect model based on between-study heterogeneity.ResultsA total of 42 studies with 7948 cases and 11866 controls were included in this meta-analysis. Among Caucasians, the CA27 allele of the IL10.G microsatellites (OR 2.38, 95% CI 1.01-5.62), the G allele of the IL-10 -1082G/A polymorphism (G vs. A: OR 1.21, 95% CI 1.02-1.44; GG vs. AA: OR 1.45, 95% CI 1.16-1.82; GG+GA vs. AA: OR 1.16, 95% CI 1.03-1.29) and its associated haplotype -1082G/-819C/-592C (OR 1.25, 95% CI 1.10-1.42) were associated with increased SLE susceptibility without or with unimportant between-study heterogeneity. Removing studies deviating from Hardy-Weinberg equilibrium (HWE) hardly changed these results. Among Asians, the CA21 allele of the IL-10.G microsatellites (OR 1.28, 95% CI 1.02-1.60) and the -1082G/-819C/-592C haplotype (OR 1.24, 95% CI 1.00-1.53) were associated with increased SLE susceptibility, but with substantial between-study heterogeneity or sensitive to HWE status. Removing studies deviating from HWE also produced statistically significant associations of the IL-10 -1082G/A (GG vs. AA: OR 3.21, 95% CI 1.24-8.28; GG vs. AA+GA: OR 2.85, 95% CI 1.19-6.79) and -592C/A polymorphisms (CC+CA vs. AA: OR 0.69, 95% CI 0.51-0.94) with SLE among Asians.ConclusionThis meta-analysis showed that the IL10.G microsatellites, the IL-10 -1082G/A and -592C/A polymorphisms and the haplotype -1082G/-819C/-592C are associated with SLE susceptibility. Besides, this is the first time to report an association between the CA27 allele of the IL-10.G microsatellites and SLE among Caucasians. Further studies are needed to confirm these findings.

Project description:BackgroundThis study evaluated the association between peptidyl arginine deiminase type IV (PADI4) and interleukin 33 (IL-33) with systemic lupus erythematosus (SLE) and juvenile idiopathic arthritis (JIA).MethodWe searched the PubMed, Web of Science, Embase and Cochrane Library databases to retrieve articles published up to January 20, 2023. Stata/SE 17.0 (College Station, TX) software was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). The cohort study, case-control study focusing on the PADI4, IL-33 polymorphism, and SLE, JIA were retrieved. The data included basic information of each study and the genotypes and allele frequencies.ResultsStudies in PADI4 rs2240340 = 2 and 3 IL-33(rs1891385 = 3, rs10975498 = 2, rs1929992 = 4) were found in 6 articles. Overall, only the IL-33 rs1891385 show significant association between SLE in all 5 models. The results were OR (95% CI) = 1.528 (1.312, 1.778), P = .000 in Allele model (C vs A), OR (95% CI) =1.473 (1.092, 1.988), P = .000 in Dominant model (CC + CA vs AA), 2.302 (1.583, 3.349), P = .000 in Recessive model (CC vs CA + AA), 2.711 (1.845, 3.983), P = .000 in Homozygote model (CC vs AA), 5.568 (3.943, 7.863), P = .000 in Heterozygote model (CA vs AA). PADI4 rs2240340, IL-33 rs10975498, IL-33 rs1929992 were not found to be association with the risk of SLE and JIA. In gene model, statistically significant association was found between IL-33 rs1891385 and SLE in sensitivity analysis. Egger's publication bias plot showed there was no publication bias (P = .165). Only in recessive model the heterogeneity test was significant (I2 = 57.9%, P ≤ .093) of IL-33 rs1891385.ConclusionThe current study suggests that in all 5 model, IL-33 rs1891385 polymorphism may be associated with genetic susceptibility to SLE. There was unclear association found between PADI4 rs2240340, IL-33 rs10975498, and IL-33 rs1929992 polymorphisms and SLE and JIA. Due to the limitations of included studies and the risk of heterogeneity, additional research is required to confirm our findings.Prospero registration numberCRD42023391268.

Dataset Information

Impact of IL-10 gene polymorphisms and its interaction with environment on susceptibility to systemic lupus erythematosus.

Publications

Impact of IL-10 gene polymorphisms and its interaction with environment on susceptibility to systemic lupus erythematosus.

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