Dataset Information

Functional Genetic Polymorphisms in the IL1RL1-IL18R1 Region Confer Risk for Ocular Behcet's Disease in a Chinese Han Population.

ABSTRACT: Single nucleotide polymorphisms (SNPs) in the IL1RL1-IL18R1 region are associated with various immune-mediated diseases. This study was carried out to investigate the causal variant for ocular Behçet's disease (BD) and elucidate its target genes in the IL1RL1-IL18R1 region. Nine candidate functional SNPs were prioritized with bioinformatics analysis, followed by a two-stage association study in 694 ocular BD patients and 1,458 unaffected controls. Functional studies were performed in the peripheral blood mononuclear cells (PBMCs) of 45 healthy men and 16 active male BD patients. Genotyping was performed using the MassARRAY System. The mRNA expressions of IL1RL1, IL18R1, IL18RAP, and SLC9A4 were assayed by real-time PCR and secretion of cytokines was examined by ELISA. Significantly lower frequencies of the rs12987977 GG genotype/G allele (P c = 8.93 × 10-7, OR = 0.39; P c = 2.60 × 10-3, OR = 0.77, respectively), rs12999364 TT genotype/T allele (P c = 3.15 × 10-4, OR = 0.51; P c = 1.13 × 10-2, OR = 0.80, respectively), and rs4851569 AA genotype/A allele (P c = 3.29 × 10-4, OR = 0.52; P c = 9.72 × 10-3, OR = 0.80, respectively) were observed in BD patients compared with the controls. Functional experiments revealed a downregulation of IL1RL1, IL18R1, and SLC9A4 and a decreased secretion of IFN-? in the anti-CD3/CD28 antibody-treated PBMCs as well as a decreased production of TNF-? in the lipopolysaccharide (LPS)-stimulated PBMCs in carriers of the protective homozygous rs12987977/GG genotype compared with the TT genotype. Our findings show that functional SNPs-rs12987977, rs12999364, and rs4851569-in the IL1RL1-IL18R1 region confer susceptibility to ocular BD in a Chinese Han population. And IL1RL1, IL18R1, and SLC9A4 may be the target genes of rs12987977.

SUBMITTER: Tan X

PROVIDER: S-EPMC7350896 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Functional Genetic Polymorphisms in the IL1RL1-IL18R1 Region Confer Risk for Ocular Behçet's Disease in a Chinese Han Population.

Tan Xiao X Zhou Qingyun Q Lv Meng M Tan Handan H Wang Qingfeng Q Zhang Liming L Cao Qingfeng Q Yuan Gangxiang G Su Guannan G Kijlstra Aize A Yang Peizeng P

Frontiers in genetics 20200703

Single nucleotide polymorphisms (SNPs) in the IL1RL1-IL18R1 region are associated with various immune-mediated diseases. This study was carried out to investigate the causal variant for ocular Behçet's disease (BD) and elucidate its target genes in the IL1RL1-IL18R1 region. Nine candidate functional SNPs were prioritized with bioinformatics analysis, followed by a two-stage association study in 694 ocular BD patients and 1,458 unaffected controls. Functional studies were performed in the periphe ...[more]

PMID: 32719716

Similar Datasets

Project description:Background: Lung cancer is one of the most common human malignant diseases. In this study, we aimed to explore the association between IL1RL1 genetic polymorphisms and lung cancer risk in the Chinese Han population. Methods: We selected and genotyped six SNPs in the IL1RL1 gene using the Agena MassARRAY system in 507 lung cancer patients and 507 healthy controls. The association between IL1RL1 variants and lung cancer risk was assessed using logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Multi-factor dimensionality reduction (MDR) was used to analyze the impact of SNP-SNP interactions on the risk of lung cancer. Results: The results of overall analysis indicated that rs12479210 (T vs. C: OR = 1.42, FDR-p = 0.002; TC vs. CC: OR = 1.70, FDR-p < 0.0001; TT vs. CC: OR = 1.77, FDR-p = 0.032; TT-TC vs. CC: OR = 1.71, FDR-p = 0.001; additive: OR = 1.44, FDR-p = 0.001) and rs1420101 (T vs. C: OR = 1.31, FDR-p = 0.036; TT-TC vs. CC: OR = 1.42, FDR-p = 0.031; additive: OR = 1.30, FDR-p = 0.030) were associated with an increased the risk of lung cancer among the Chinese Han population. Stratified analysis also found the association between these two SNPs and lung cancer risk. However, there were no significant association observed between the other four SNPs (rs3771180, rs3771175, rs10208293, and rs10197862) in IL1RL1 and lung cancer risk. Furthermore, MDR analysis showed that rs12479210 was the best single model with the highest testing accuracy (0.566) and perfect CVC (10/10) for predicting lung cancer risk. The expression level of the IL1RL1 gene is lower in lung cancer tissue than normal tissue, and there are significant differences in the expression levels of IL1RL1 between rs12479210 and rs1420101 genetypes in lung cancer tissue (p < 0.05). Conclusion: Our findings suggest that IL1RL1 genetic variants (rs12479210 and rs1420101) are associated with an increased lung cancer risk in the Chinese Han population. These risk variants may serve as biomarkers for the prevention and treatment of lung cancer.

Dataset Information

Functional Genetic Polymorphisms in the IL1RL1-IL18R1 Region Confer Risk for Ocular Behcet's Disease in a Chinese Han Population.

Publications

Functional Genetic Polymorphisms in the IL1RL1-IL18R1 Region Confer Risk for Ocular Behçet's Disease in a Chinese Han Population.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets