The rs2228145 polymorphism in the interleukin-6 receptor and its association with long-term prognosis after myocardial infarction in a pilot study

Szpakowicz, Anna; Pepiński, Witold; Waszkiewicz, Ewa; Skawrońska, Małgorzata; Niemcunowicz‐Janica, Anna; Musiał, Włodzimierz J.; Kamiński, Karol

doi:10.5114/aoms.2016.58636

Cited by 5 publications

(3 citation statements)

References 34 publications

(38 reference statements)

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“…Of note, it has been demonstrated that SNPs in the IL6R gene (e.g., Asp358Ala [rs2228145]; ref. 33) can influence inflammation in the context of various inflammatory (34)(35)(36) and cardiac disorders (37)(38)(39). In summary, these findings offer insights into the role of the ectopic membrane-bound IL6R upregulation in PA-SMCs in PAH.…”

Section: Discussionmentioning

confidence: 80%

Ectopic upregulation of membrane-bound IL6R drives vascular remodeling in pulmonary arterial hypertension

Tamura¹,

Phan²,

Tu³

et al. 2018

Journal of Clinical Investigation

131

115

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Pulmonary arterial hypertension (PAH) is characterized by a progressive accumulation of pulmonary artery smooth muscle cells (PA-SMCs) in pulmonary arterioles leading to the narrowing of the lumen, right heart failure, and death. Although most studies have supported the notion of a role for IL-6/glycoprotein 130 (gp130) signaling in PAH, it remains unclear how this signaling pathway determines the progression of the disease. Here, we identify ectopic upregulation of membrane-bound IL-6 receptor (IL6R) on PA-SMCs in PAH patients and in rodent models of pulmonary hypertension (PH) and demonstrate its key role for PA-SMC accumulation in vitro and in vivo. Using Sm22a-Cre Il6rfl/fl, which lack Il6r in SM22A-expressing cells, we found that these animals are protected against chronic hypoxia-induced PH with reduced PA-SMC accumulation, revealing the potent pro-survival potential of membrane-bound IL6R. Moreover, we determine that treatment with IL6R-specific antagonist reverses experimental PH in two rat models. This therapeutic strategy holds promise for future clinical studies in PAH.

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Section: Discussionmentioning

confidence: 80%

Ectopic upregulation of membrane-bound IL6R drives vascular remodeling in pulmonary arterial hypertension

Tamura¹,

Phan²,

Tu³

et al. 2018

Journal of Clinical Investigation

131

115

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“…Several studies have reported an association between the IL-6 gene (-174G>C) polymorphism and CAD, HF [13,14]. However, other studies have reported no such relation [15][16][17][18].…”

Section: Resultsmentioning

confidence: 99%

Relationship Between Interleukin-6 Gene Polymorphism and Heart Failure in Patients With Coronary Artery Disease and Obesity

et al. 2020

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The aim: To examine the association between polymorphisms of the IL-6 gene promoter and HF in patients with CAD and obesity. Material and methods: 222 patients with coronary artery disease and obesity were identified. Comparison group consisted of 115 patients with coronary artery disease with normal body weight. The groups were comparable in age and sex. The exclusion group consisted of patients with severe concomitant diseases of the respiratory and digestive organs, kidneys and people with cancer. One single nucleotide polymorphisms in the interleukin-6 promoter region was analyzed. Odds ratio (OR) and 95 % confident interval (95 % CI) were calculated. Results: The combined course of coronary artery disease and obesity was characterized by the detection of allele C in 62 patients (27.93 %), allele G – in 160 patients (72.07 %), and genotypes CC, CG and GG – at 24 (10.81 %), 67 (30.18 %) and 131 (59.01 %) patients respectively. The results showed that the −174G allele and GG genotype in patients with coronary artery disease and obesity were associated with heart failure (OR = 2.55, 95% CI = [1.72-3.79], χ2 = 22.8; p<0.05) and (OR = 11.95, 95% CI = [3.41-41.91], χ2 = 22.5; p<0.05), whereas allele C−174 was associated with a decrease in the risk of heart failure (OR = 0.39, 95% CI = [0.26-0.58 ], χ2 = 22.75, p<0.05). Conclusions: The obtained results testify that the −174G>C polymorphism in the interleukin-6 gene is significantly associated with increased risk of heart failure in patients with coronary artery disease and obesity.

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“…The frequency of this allele in Poles is very close to the average (36.0%) of five European-derived populations from the 1000 Genomes project, ranging from 33.2% to 40.1%. This highlights the genetic variability across populations and the need for a nuanced understanding of genetic factors in disease predisposition [51][52][53][54][55][56].…”

Section: Discussionmentioning

confidence: 99%

No Association of Polymorphisms in the Genes Encoding Interleukin-6 and Interleukin-6 Receptor Subunit Alpha with the Risk of Keloids in Polish Patients

Dmytrzak,

Lewandowska,

Boroń

et al. 2024

IJMS

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A keloid is a benign fibroproliferative hypertrophy of scar tissue that extends outside the original wound and invades adjacent healthy skin. Keloid formation is thought to be a complex process including overactivity of the interleukin-6 signaling pathway and genetic susceptibility. The aim of the study was to investigate possible associations between rs1800797, rs1800796, and rs1800795 polymorphisms in the promoter of the IL6 gene encoding interleukin-6 and the rs2228145 polymorphism in the IL6R gene encoding the interleukin-6 receptor subunit alpha with the predisposition to keloids in Polish patients. The genetic polymorphisms were identified either using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) or sequencing of samples of genomic DNA extracted from blood leukocytes of 86 adult patients with keloids and 100 newborns comprising a control group. No significant differences in the distributions of IL6 or IL6R alleles or genotypes were found between keloid patients and newborn controls. There were also no significant differences between both groups in the distribution of IL6 haplotypes. The IL6 rs1800797, rs1800796 and rs1800795 and IL6R rs2228145 polymorphisms were not found to predispose individuals in the study group to keloids. IL6 promoter haplotypes were not found to be associated with a higher risk of keloids in the studied group.

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The rs2228145 polymorphism in the interleukin-6 receptor and its association with long-term prognosis after myocardial infarction in a pilot study

Cited by 5 publications

References 34 publications

Ectopic upregulation of membrane-bound IL6R drives vascular remodeling in pulmonary arterial hypertension

Ectopic upregulation of membrane-bound IL6R drives vascular remodeling in pulmonary arterial hypertension

Relationship Between Interleukin-6 Gene Polymorphism and Heart Failure in Patients With Coronary Artery Disease and Obesity

No Association of Polymorphisms in the Genes Encoding Interleukin-6 and Interleukin-6 Receptor Subunit Alpha with the Risk of Keloids in Polish Patients

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