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Polymorphisms and plasma levels of IL-27: impact on genetic susceptibility and clinical outcome of bladder cancer.

ABSTRACT: Interleukin-27 (IL-27) has been recognized as a pleiotropic cytokine with both pro- and anti-inflammatory properties. Few studies have investigated polymorphisms and serum/plasma levels of IL-27 in diseases including cancers. This study has analyzed the associations of IL-27 gene polymorphisms, as well as plasma levels of IL-27, with susceptibility to bladder cancer and clinical outcome.Three hundred and thirty-two patients (nonmuscle-invasive bladder cancer (NMIBC)/muscle-invasive bladder cancer (MIBC): 176/156) included in a 60-month follow-up program and 499 controls were enrolled. Two single nucleotide polymorphisms (SNPs), rs153109 and rs17855750, were genotyped by polymerase chain reaction (PCR) -restriction fragment length polymorphism (RFLP) method. Plasma concentration of IL-27 was determined by ELISA in 124 patients (NMIBC/MIBC: 50/74) and 151 controls.Significantly increased risk for bladder cancer was associated with AG/GG genotypes of rs153109 (P = 0.029). No GG genotype of rs17855750 was observed in controls, while 4 patients were found to be GG homozygotes, suggesting GG genotype may be associated with bladder cancer risk (P = 0.006). For bladder cancer patients, SNP rs17855750 was also associated with increased risk for MIBC. For MIBC patients, but not NMIBC, TG/GG genotypes of rs17855750 turned out to be a protective factor for overall survival (P = 0.035). Significantly reduced plasma levels of IL-27 were observed in both NMIBC and MIBC patients compared with controls (P < 0.0001).Our data suggest that polymorphisms and reduced plasma levels of IL-27 may predict the susceptibility to bladder cancer, and rs17855750 may be a useful marker to distinguish patients with high risk of death.

SUBMITTER: Zhou B

PROVIDER: S-EPMC4445811 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Polymorphisms and plasma levels of IL-27: impact on genetic susceptibility and clinical outcome of bladder cancer.

Zhou Bin B Zhang Peng P Tang Tielong T Liao Hong H Zhang Kui K Pu Yan Y Chen Peng P Song Yaping Y Zhang Lin L

BMC cancer 20150527

<h4>Background</h4>Interleukin-27 (IL-27) has been recognized as a pleiotropic cytokine with both pro- and anti-inflammatory properties. Few studies have investigated polymorphisms and serum/plasma levels of IL-27 in diseases including cancers. This study has analyzed the associations of IL-27 gene polymorphisms, as well as plasma levels of IL-27, with susceptibility to bladder cancer and clinical outcome.<h4>Methods</h4>Three hundred and thirty-two patients (nonmuscle-invasive bladder cancer (N ...[more]

PMID: 26014498

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Project description:(1) Background: interleukin 23 (IL-23) and interleukin 27 (IL-27) modulate the activity of T helper 17 cells (Th17) with critical roles in autoimmune diseases and multiple sclerosis (MS). The genes responsible for cytokine generation are highly influenced by the presence of single nucleotide polymorphisms (SNP) in main regions such as regulatory sequences or in promoter regions, contributing to disease susceptibility and evolution. The present study analyzed the associations of IL-23 and IL-27 SNPs with susceptibility to multiple sclerosis. (2) Methods: We performed a case-control study including 252 subjects: 157 patients diagnosed with MS and 95 controls. We used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to determine the genotypes for IL-27 T4730C (rs 181206), IL-27 A964G (rs 153109), and IL-23 receptor gene (IL-23R) G1142A (rs 11209026). (3) Results: The IL27-T4730C gene polymorphism was significantly associated with an increased odds of MS under the dominant genetic model (TC + CC variant genotypes, adjusted odds ratio OR = 4.06, 95% CI: 2.14-7.83, p-value = 0.000007, Q-value = 0.000063). Individuals carrying the IL-27 A924G variant (AG + GG) genotype presented higher odds of MS compared to non-carriers under the dominant model (adjusted OR = 1.93, 95% CI: 1.05-3.51, p-value = 0.0324, Q-value = 0.05832) and the allelic genetic model (unadjusted p-value = 0.015, OR = 1.58, 95% CI: 1.09-2.28), while IL-23-R381Q SNP conferred a decreased odds of MS under a codominant model of inheritance (adjusted OR = 0.26, 95% CI: 0.08-0.92, p-value = 0.0276, Q-value = 0.058) and an allelic model (unadjusted p-value = 0.008, OR = 0.23, 95% CI: 0.07-0.75). In an additive model with adjustment for age group (≤40 years vs. >40 years), sex and smoking, patients carrying the G-C (A964G, T4730C) haplotype had a 3.18 increased risk (95% CI: 1.74-5.81, p < 0.001) to develop multiple sclerosis. (4) Conclusions: The results of the current study showed a significant relationship of IL-27-A964G and IL-27-T4730C polymorphisms with increased risk of MS, and also the protective role of the IL-23-R381Q polymorphism. Moreover, the haplotype-based analysis proposed the mutant G-C (A924G, T4730C) as a significant risk haplotype for the development of MS.

Project description:BackgroundInterleukin-32 (IL-32) has long been proposed as a biomarker for coronary artery disease (CAD). We aimed to evaluate the association between IL-32 levels and coronary stenosis severity, IL-32 polymorphisms rs28372698 and rs4786370, and CAD susceptibility.MethodsA total of 362 patients with definite or suspected CAD that underwent angiography were recruited (CAD group, n = 175; nonobstructive CAD group, n = 56; control group, n = 131). The severity of coronary stenosis was assessed using the Gensini score and the number of diseased vessels. IL-32 levels were determined using enzyme-linked immunosorbent assay. Gene polymorphisms were genotyped using PCR and sequencing techniques.ResultsIL-32 levels were significantly different at different levels of coronary artery stenosis (p < 0.05), and logIL-32 was positively correlated with the Gensini score (r = 0.357, p < 0.01). Multivariate logistic regression analysis revealed that IL-32 was independently associated with CAD (OR = 6.526, 95% CI: 3.344-12.739, p < 0.01). The receiver operating characteristic analysis revealed the area under the curve for discriminating the CAD and Gensini score were 0.605 and 0.613, respectively. Furthermore, IL-32 levels were significantly higher before percutaneous coronary intervention (PCI) than at 7 days post-PCI (p = 0.012). The homozygous TT genotype and T allele of rs28372698 were found to be associated with increased risk of CAD, while TT homozygosity and the T allele of rs4786370 with reduced risk of CAD (p < 0.05). However, both SNPs had no obvious effect on IL-32 levels or coronary stenosis severity in patients with CAD.ConclusionTo the best of our knowledge, our study is the first to show that rs28372698 and rs4786370 are associated with CAD susceptibility in Chinese Han population. We also suggest that plasma IL-32 levels may be indicative of coronary artery stenosis and the efficacy of PCI and provide guidance for risk stratification and disease management.

Dataset Information

Polymorphisms and plasma levels of IL-27: impact on genetic susceptibility and clinical outcome of bladder cancer.

Publications

Polymorphisms and plasma levels of IL-27: impact on genetic susceptibility and clinical outcome of bladder cancer.

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