Interleukin 6 (rs1800795) gene polymorphism is associated with cardiovascular diseases: a meta-analysis of 74 studies with 86,229 subjects

González‐Castro, Thelma Beatriz; Hernández‐Díaz, Yazmín; Pérez-Hernández, Nonanzit; Tovilla-Zárate, Carlos Alfonso; Juárez‐Rojop, Isela Esther; López‐Narváez, María Lilia; Blachman‐Braun, Ruben; Posadas-Sánchez, Rosalinda; Vargas‐Alarcón, Gilberto; García-Flores, Esbeidy; Cazarín-Santos, Benny Giovanni; Borgonio-Cuadra, Verónica Marusa; Reyes-López, Pedro Antonio; Rodrı́guez-Pérez, José Manuel

doi:10.17179/excli2019-1248

Cited by 19 publications

(16 citation statements)

References 87 publications

(266 reference statements)

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“…In addition, there was a significant association between all-cause mortality and IL1B rs16944. Of note, we failed to replicate some of the previously reported associations with CVD events ( IL6 rs1800795, IL6 rs228145, IL10 rs1800872, IL17A rs2275913, VDR rs2228570, ARL15 rs4311394, CDKN2B-AS1 rs1333049, TNFRSF11B rs2073618) [ 18 – 36 ].…”

Section: Discussioncontrasting

confidence: 63%

“…These SNPs were based on multi-functional gene sets, including 10 SNPs from eight genes encoding interleukins or interleukin receptors. Interleukins play an important role in inflammation [ 16 ], a known risk factor for CHD [ 17 ], with several previously reported in association with CHD— IL6 rs1800795 [ 18 ], IL6R rs2228145 [ 19 ], IL10 rs1800872 [ 20 ] and IL17A rs2275913 [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

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Association of TGFB1 rs1800469 and BCMO1 rs6564851 with coronary heart disease and IL1B rs16944 with all-cause mortality in men from the Northern Ireland PRIME study

Mooney

Linden²,

Winning³

et al. 2022

PLoS ONE

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Background Historically, high levels of morbidity and mortality have been associated with cardiovascular disease in the Northern Ireland population. Previously reported associations between single nucleotide polymorphisms (SNPs) and cardiovascular disease within other populations have not always been consistent. Objective To investigate associations between 33 SNPs with fatal or non-fatal incident coronary heart disease (CHD) events and all-cause mortality in the Northern Irish participants of the Prospective Epidemiological Study of Myocardial Infarction (PRIME). Method Phase 2 of the PRIME study prospectively evaluated 2,010 men aged 58–74 years in Northern Ireland for more than 10 years for incident CHD events (myocardial infarction, percutaneous coronary intervention, coronary artery bypass, and cardiac death) and more than 15 years for all-cause mortality. SNPs previously reported in association with cardiovascular outcomes were evaluated against incident CHD events and all-cause mortality using Cox’s proportional hazards models adjusted for established cardiovascular disease risk factors. Results During the follow-up period, 177 incident CHD events were recorded, and 821 men died. Both BCMO1 rs6564851 (Hazard ratio [HR] = 0.76; 95% confidence intervals [CI]: 0.60–0.96; P = 0.02) and TGFB1 rs1800469 (HR = 1.30; CI: 1.02–1.65; P = 0.04) were significantly associated with incident CHD events in adjusted models. Only IL1B rs16944 was significantly associated with all-cause mortality (HR = 1.18; CI: 1.05–1.33; P = 0.005). No associations remained significant following Bonferonni correction for multiple testing. Conclusion We report a novel association between BCMO1 rs6564851 and risk of incident CHD events. In addition, TGFB1 rs1800469 and IL1B rs16944 were associated with the risk of incident CHD events and all-cause mortality outcomes respectively, supporting previously reported associations.

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Section: Discussioncontrasting

confidence: 63%

Section: Introductionmentioning

confidence: 99%

Association of TGFB1 rs1800469 and BCMO1 rs6564851 with coronary heart disease and IL1B rs16944 with all-cause mortality in men from the Northern Ireland PRIME study

Mooney

Linden²,

Winning³

et al. 2022

PLoS ONE

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“…Afterward, we explored this issue considering the ethnicity of our population in study. Being a Caucasian population, the literature data have reported a significant association only under homozygous recessive model (TT and CC) of the polymorphisms examined in our study, and particularly for -174G>C (rs1800795) IL-6 polymorphism [16].…”

Section: Discussionmentioning

confidence: 42%

“…Its crucial role in CVD has been proven by prospective studies, demonstrating how high basal plasmatic levels of IL-6, having pro-inflammatory and procoagulant effects, are potent CVD risk factors [40][41][42][43]. In addition, other pieces of evidence arrive from the significant results of a recent meta-analysis of 74 studies, showing a significant association of the -174C allele (rs1800795) of IL-6 gene polymorphism with several CVD, including myocardial infarction, coronary artery disease, ischemic stroke, peripheral arterial occlusive disease, and heart failure [16], in spite of functional effect of this allele on IL-6 serum level [44]. Recent studies have also confirmed its role in abdominal aortic aneurysms [42,43], Here, we demonstrated the role of IL-6 and IL-1B in TAAA disease.…”

Section: Discussionmentioning

confidence: 99%

“…[6] Many inflammatory pathways have been documented to contribute to CVD onset and progression, including TLR-4/NF-kβ pathway [8,9], TLR-2 [10], TGF-β1 [11], CCR5 [12], CRP [13]. Recently, pro-and anti-inflammatory cytokines, such as interleukin-(IL)-10 [14] and IL-6 [15], have been associated with CVD onset and progression, and current meta-analyses [16][17][18][19] have also confirmed the relationship of some functional polymorphisms in pro-inflammatory cytokine genes with the significant increase in the susceptibility to several CVD, abdominal aortic aneurysms included. Consistent with this, a prospective multicenter observational open-label cohort study of patients, the MA3RS study [20], has demonstrated the importance of monitoring aortic wall inflammation via ultrasmall superparamagnetic particles of iron oxide-enhanced magnetic resonance imaging for significantly predicting both the rate of aneurysm growth, and the risk of severe complications, such as aneurysm rupture [20].…”

Section: Introductionmentioning

confidence: 99%

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Polymorphisms of Pro-Inflammatory IL-6 and IL-1β Cytokines in Ascending Aortic Aneurysms as Genetic Modifiers and Predictive and Prognostic Biomarkers

et al. 2021

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Background: Previous studies have demonstrated that polymorphisms involved in immune genes can affect the risk, pathogenesis, and outcome of thoracic ascending aortic aneurysms (TAAA). Here, we explored the potential associations of five functional promoter polymorphisms in interleukin-6 (IL-6), IL-1B, IL-1A, IL-18, and Tumor necrosis factor (TNF)A genes with TAAA. Methods: 144 TAAA patients and 150 age/gender matched controls were typed using KASPar assays. Effects on telomere length and levels of TAAA related histopathological and serological markers were analyzed. Results: Significant associations with TAAA risk were obtained for IL-6 rs1800795G>C and IL-1B rs16944C>T SNPs. In addition, the combined rs1800795C/rs16944T genotype showed a synergic effect on TAAA pathogenesis and outcome. The combined rs1800795C/rs16944T genotype was significantly associated with: (a) higher serum levels of both cytokines and MMP-9 and -2; (b) a significant CD3+CD4+CD8+ CD68+CD20+ cell infiltration in aorta aneurysm tissues; (c) a significant shorter telomere length and alterations in telomerase activity. Finally, it significantly correlated with TAAA aorta tissue alterations, including elastic fragmentation, medial cell apoptosis, cystic medial changes, and MMP-9 levels. Conclusions: the combined rs1800795C/rs16944T genotype appears to modulate TAAA risk, pathogenesis, and outcome, and consequently can represent a potential predictive and prognostic TAAA biomarker for individual management, implementation of innovative treatments, and selection of the more proper surgical timing and approaches.

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Making sense of IL‐6 signalling cues in pathophysiology

et al. 2021

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Unravelling the molecular mechanisms that account for functional pleiotropy is a major challenge for researchers in cytokine biology. Cytokine–receptor cross‐reactivity and shared signalling pathways are considered primary drivers of cytokine pleiotropy. However, reports epitomized by studies of Jak‐STAT cytokine signalling identify interesting biochemical and epigenetic determinants of transcription factor regulation that affect the delivery of signal‐dependent cytokine responses. Here, a regulatory interplay between STAT transcription factors and their convergence to specific genomic enhancers support the fine‐tuning of cytokine responses controlling host immunity, functional identity, and tissue homeostasis and repair. In this review, we provide an overview of the signalling networks that shape the way cells sense and interpret cytokine cues. With an emphasis on the biology of interleukin‐6, we highlight the importance of these mechanisms to both physiological processes and pathophysiological outcomes.

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Interleukin 6 (rs1800795) gene polymorphism is associated with cardiovascular diseases: a meta-analysis of 74 studies with 86,229 subjects

Cited by 19 publications

References 87 publications

Association of TGFB1 rs1800469 and BCMO1 rs6564851 with coronary heart disease and IL1B rs16944 with all-cause mortality in men from the Northern Ireland PRIME study

Association of TGFB1 rs1800469 and BCMO1 rs6564851 with coronary heart disease and IL1B rs16944 with all-cause mortality in men from the Northern Ireland PRIME study

Polymorphisms of Pro-Inflammatory IL-6 and IL-1β Cytokines in Ascending Aortic Aneurysms as Genetic Modifiers and Predictive and Prognostic Biomarkers

Making sense of IL‐6 signalling cues in pathophysiology

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