Association between polymorphisms in<i>IL27</i>and risk for CHD in a Chinese population

Zhang, Danyan; Ma, Mingfu; Yang, Yiqin; Wan, Ling; Yang, Z X; Lv, Jing; Li, Xinsheng; Yang, Hao; Huang, Pei; Li, Lianbing

doi:10.1017/s1047951115000037

Cited by 7 publications

(5 citation statements)

References 37 publications

(63 reference statements)

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“…Recent genetic association studies have confirmed that the IL-27 rs153109 polymorphism affects mRNA expression and influences patient predisposition to various inflammation-related diseases [ 21 – 23 , 45 , 46 ]. A recent study showed that the rs153109 promoter polymorphism of IL-27 probably influences gene transcription by altering its binding to transcription factors and that the AA genotype or A allele confers susceptibility to asthma [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

The interleukin-27 -964A>G polymorphism enhances sepsis-induced inflammatory responses and confers susceptibility to the development of sepsis

Zhang

et al. 2018

Crit Care

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BackgroundPrevious studies have identified critical roles of IL-27 in the pathological mechanisms of sepsis, and blockade of IL-27 may be a promising alternative therapy for sepsis. The purpose of this study was to evaluate the clinical relevance of IL-27 genetic polymorphisms in sepsis and to further characterize their effect on IL-27 expression and inflammatory processes following sepsis.MethodsA total of 885 septic patients and 1101 healthy controls were enrolled and genotyped for IL-27 genetic variants (rs153109/−964A > G and rs17855750/2905 T > G). Quantitative real-time PCR and enzyme-linked immunosorbent assays were performed to detect IL-27 expression and cytokine production. The effect of the rs153109 polymorphism on IL-27 promoter activity was evaluated using a luciferase reporter assay, and THP-1 cell apoptosis was calculated using an annexin V apoptosis assay.ResultsNo significant differences in the genotype/allele frequencies were observed between patients with sepsis and healthy controls, suggesting that these two IL-27 polymorphisms may not influence susceptibility to sepsis. The -964AA genotype was overrepresented in patients with severe sepsis/septic shock relative to patients with the sepsis subtype, and the A allele was significantly associated with 28-mortality in sepsis. Patients carrying the -964AA genotype exhibited significantly higher expression levels of IL-27 than the GA/GG genotype carriers. The results of an in vitro (lipopolysaccharide (LPS))-stimulated experiment showed that this sepsis-associated high-risk AA genotype significantly increased IL-27 levels and enhanced TNF-α and IL-1β production in the peripheral blood mononuclear cells (PBMCs) upon exposure to LPS in vitro. Furthermore, luciferase reporter assays indicated that the high-risk -964A allele resulted in increased promoter activities compared to the non-risk allele in THP-1 and 293 T cells. Additionally, IL-27 treatment significantly enhanced TNF-α and IL-6 secretion and apoptosis of THP-1 cells upon LPS stimulation.ConclusionsThese results provided evidence that the IL-27 -964A > G polymorphism functionally enhanced IL-27 expression and promoted sepsis-induced inflammatory responses, which ultimately resulted in promoting the progression of sepsis and poor prognosis.Electronic supplementary materialThe online version of this article (10.1186/s13054-018-2180-0) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

The interleukin-27 -964A>G polymorphism enhances sepsis-induced inflammatory responses and confers susceptibility to the development of sepsis

Zhang

et al. 2018

Crit Care

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“…The associations between IL27p28 polymorphisms and the risk of various diseases such as asthma [ 13 – 18 , 36 – 43 ], chronic obstructive pulmonary disease [ 13 – 18 , 37 – 43 ], coronary heart disease [ 13 – 18 , 38 – 43 ], rheumatoid arthritis [ 14 – 18 , 38 – 43 ], inflammatory bowel disease [ 14 – 18 , 39 – 43 ], pulmonary tuberculosis [ 15 – 18 , 40 – 43 ], allergic rhinitis [ 15 – 18 , 41 – 43 ], HCV infection [ 16 – 18 , 41 – 43 ], and several tumors (e.g., esophageal cancer [ 16 – 18 , 42 , 43 ], nasopharyngeal carcinoma [ 16 , 17 , 42 , 43 ], ovarian [ 16 , 17 ], and bladder [ 16 ] cancer) have also been detected. Therefore, IL27p28 polymorphisms have been investigated in this study.…”

Section: Discussionmentioning

confidence: 99%

“…Statistical analyses were performed as previously described [ 13 , 15 , 16 ] using the GraphPad Prism version 5.0 software (GraphPad Software Inc., San Diego, CA, USA). Comparisons were carried out using Student's t -tests or chi-square ( χ 2 ) tests for 2-group comparisons when appropriate.…”

Section: Methodsmentioning

confidence: 99%

Interleukin-27 as a Novel Biomarker for Early Cardiopulmonary Failure in Enterovirus 71-Infected Children with Central Nervous System Involvement

Huang¹,

Lee

et al. 2016

Mediators of Inflammation

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Enterovirus 71 (EV71) is a major pathogen for severe hand, foot, and mouth disease (HFMD), which leads to severe neurological complications and has high morbidity and mortality. Reliable biomarker for the prediction of deterioration in EV71-infected children with central nervous system (CNS) involvement may reduce the cardiopulmonary failure and mortality. Here, we found that serum IL-27 levels were significantly higher in stage III EV71-infected HFMD patients with early cardiopulmonary failure and strong correlation with CRP levels. IL27p28 polymorphisms (rs153109, rs17855750, and rs181206) did not influence IL-27 production, and these three SNPs were not associated with EV71 infection risk and clinical stage. IL-27 can be used as an prediction indicator for early cardiopulmonary failure in EV71-infected children with CNS involvement.

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“…Polymorphisms in the IL-27p28 gene have been associated with risk of inflammatory bowel disease 131 , RA 132 , asthma 130 , allergic rhinitis 133 , chronic obstructive pulmonary disease 134 , and with protection of ulcerative colitis 135 . In a Chinese casecontrol study, an association of atrial septal defects and ventricular septal defect with the G allele of rs153109 polymorphism was reported; no association was found with the rs17855750 polymorphism 136 . In a large number of CAD cases belonging to the GeneID Chinese Han population, four IL-27p28 tag polymorphisms (rs181206, rs17855750, rs37833, and rs153109) were detected and after adjusting for confounding variables, the polymorphisms were not associated with CAD, age at disease onset or severity 137 .…”

Section: Il-27p28 Genementioning

confidence: 97%

Innate Immunity in Coronary Disease. The Role of Interleukin-12 Cytokine Family in Atherosclerosis

Posadas-Sánchez

Vargas‐Alarcón

2018

RIC

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Atherosclerosis is a chronic, progressive, and multifactorial disease modulated by genetic and environmental factors. In recent years, the paradigm that explained atherosclerosis as resulting from a complex interaction between factors not accessible to medical intervention, and modifiable risk factors has changed. In this paradigm, alterations in lipid metabolism were the pivotal concept of atherosclerosis as a chronic degenerative disease. In the last years, an increasing number of observations have shown that the innate and adaptive immune responses to lipoprotein deposition and oxidation in the arterial wall significantly influence atherosclerosis. Currently, it is well recognized that the pathogenesis of atherosclerosis and its complications involves the inflammatory process, which includes the participation of several cytokines. Besides the classic cytokines involved in this process, the role of the interleukin-12 (IL-12) family has been recently demonstrated. This review describes our current understanding about the role of the family of IL-12 in atherosclerosis considering the participation of the genes that encode these cytokines in the genetic susceptibility to developing this disease.

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Association between polymorphisms inIL27and risk for CHD in a Chinese population

Abstract: The 153109 of the IL27 gene may be associated with the susceptibility to CHD, including atrial septal defect and ventricular septal defect.

Cited by 7 publications

References 37 publications

The interleukin-27 -964A>G polymorphism enhances sepsis-induced inflammatory responses and confers susceptibility to the development of sepsis

The interleukin-27 -964A>G polymorphism enhances sepsis-induced inflammatory responses and confers susceptibility to the development of sepsis

Interleukin-27 as a Novel Biomarker for Early Cardiopulmonary Failure in Enterovirus 71-Infected Children with Central Nervous System Involvement

Innate Immunity in Coronary Disease. The Role of Interleukin-12 Cytokine Family in Atherosclerosis

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