Influence of the <i>IL6</i> Gene in Susceptibility to Systemic Sclerosis

Cénit, M C; Simeón, Carmen P.; Vonk, Madelon C.; Callejas-Rubio, José Luis; Espinosa, Gerard; Carreira, Patrícia; Blanco, Francisco J.; Narváez, Javier; Tolosa, Carlos; Román-Ivorra, Jose Andrés; GÓMEZ-GARCÍA, INMACULADA; García–Hernández, Francisco J.; Gallego, M.; García-Portales, Rosa; Egurbide, María Victoria; Fonollosa, V.; Peña, Paloma García de la; López‐Longo, Francisco Javier; González-Gay, Miguel Á.; Hesselstrand, Roger; Riemekasten, Gabriela; Witte, Torsten; Voskuyl, Alexandre E.; Schuerwegh, Annemie J.; Madhok, Rajan; Fonseca, Carmen; Denton, Christopher P.; Nordin, Annika; Palm, Øyvind; Laar, Jacob M van; Hunzelmann, Nicolas; Distler, Jörg H W; Kreuter, Alexander; Herrick, Ariane L.; Worthington, Jane; Koeleman, Bobby P. C.; Radstake, Timothy R. D. J.; Martı́n, Javier

doi:10.3899/jrheum.120506

Cited by 37 publications

(21 citation statements)

References 24 publications

(24 reference statements)

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“…Another limitation of this study is that by using only a few SNPs in each region, we cannot make inferences for contributions to these pain phenotypes from gene variants not in linkage disequilibrium with the selected SNPs, although the exploratory analysis with the single IL1B SNP rs1143634 suggested that other regions of this gene may play a role. Further, consistent with the notion that the inflammatory process is complex, IL6 is reported to have both pro- and anti-inflammatory effects depending on the type of injury, location, and duration; such properties could significantly complicate genetic analysis and interpretation, and might underlie the lack of significant findings for IL6 in our model (4). Also, since the majority of our participants were white (non-Hispanic) and we controlled for race in our regression analyses; we may have missed subtle influences of race on the pain phenotypes.…”

Section: Discussionsupporting

confidence: 81%

“…However the interaction for IL1B and kinesiophobia indicated that increased kinesiophobia predicted decreased pain for another genotype group: the “22” diplotype at rs16944 and rs1143627 promoter SNPs. This suggests that homozygosity for the AG haplotype (“2”) is protective for these pain measures, which is consistent with the “1” haplotype being part of a risk haplotype for osteoarthritis (4). This intriguing finding may merit further confirmatory investigation, including direct measurement of inflammatory mediators, because of the finding implicating an inflammatory pathway that reversed the adverse effects of a well-established psychological risk factor.…”

Section: Discussionsupporting

confidence: 59%

“…The haplotypes were combined into diplotypes for each subject, and these diplotypes were grouped together to represent putatively functionally-distinct groups (promoting more or less inflammation, based on prior evidence from the literature (15,16). However, at the TNF/LTA region, there was lower linkage disequilibrium and thus this locus was analyzed by individual SNPs (4). The SNPs included: IL1B (rs1143627, rs16944, rs1143634), IL6 (rs1800797, rs2069840), and the TNF/LTA region (rs1800629, rs229094, rs1800683).…”

Section: Methodsmentioning

confidence: 99%

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Inflammatory Genes and Psychological Factors Predict Induced Shoulder Pain Phenotype

George

Parr

Wallace

et al. 2014

Medicine &Amp; Science in Sports &Amp; Exercise

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Purpose The pain experience has multiple influences but little is known about how specific biological and psychological factors interact to influence pain responses. The current study investigated the combined influences of genetic (pro-inflammatory) and psychological factors on several pre-clinical shoulder pain phenotypes. Methods An exercise-induced shoulder injury model was used, and a priori selected genetic (IL1B, TNF/LTA region, IL6 single nucleotide polymorphisms, SNPs) and psychological (anxiety, depressive symptoms, pain catastrophizing, fear of pain, kinesiophobia) factors were included as the predictors of interest. The phenotypes were pain intensity (5-day average and peak reported on numerical rating scale), upper-extremity disability (5-day average and peak reported on the QuickDASH instrument), and duration of shoulder pain (in days). Results After controlling for age, sex, and race, the genetic and psychological predictors were entered separately as main effects and interaction terms in regression models for each pain phenotype. Results from the recruited cohort (n = 190) indicated strong statistical evidence for the interactions between 1) TNF/LTA SNP rs2229094 and depressive symptoms for average pain intensity and duration and 2) IL1B two-SNP diplotype and kinesiophobia for average shoulder pain intensity. Moderate statistical evidence for prediction of additional shoulder pain phenotypes included interactions of kinesiophobia, fear of pain, or depressive symptoms with TNF/LTA rs2229094 and IL1B. Conclusion These findings support the combined predictive ability of specific genetic and psychological factors for shoulder pain phenotypes by revealing novel combinations that may merit further investigation in clinical cohorts, to determine their involvement in the transition from acute to chronic pain conditions.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionsupporting

confidence: 59%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Inflammatory Genes and Psychological Factors Predict Induced Shoulder Pain Phenotype

George

Parr

Wallace

et al. 2014

Medicine &Amp; Science in Sports &Amp; Exercise

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“…The SNPs rs1800796, rs2069837, and rs10242595 have all been reported to be associated with Alzheimer’s disease and ischemic stroke [27-30], and the rs2069840 SNP has been shown to be associated with systemic sclerosis [31]. The common haplotype tagged by the SNP rs1800796 (C-572G) has been shown to be associated with an increased risk of brain infarct in elderly subjects in a cardiovascular health study [32].…”

Section: Discussionmentioning

confidence: 99%

The association between sex-related interleukin-6 gene polymorphisms and the risk for cerebral palsy

Chen

Zhang

et al. 2014

J Neuroinflammation

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BackgroundThe relationship between genetic factors and the development of cerebral palsy (CP) has recently attracted much attention. Polymorphisms in the genes encoding proinflammatory cytokines have been shown to be associated with susceptibility to perinatal brain injury and development of CP. Interleukin-6 (IL-6) is a proinflammatory cytokine that plays a pivotal role in neonatal brain injury, but conflicting results have been reported regarding the association between IL-6 single nucleotide polymorphisms (SNPs) and CP. The purpose of this study was to analyze IL-6 gene polymorphisms and protein expression and to explore the role of IL-6 in the Chinese CP population.MethodsA total of 753 healthy controls and 713 CP patients were studied to detect the presence of five SNPs (rs1800796, rs2069837, rs2066992, rs2069840, and rs10242595) in the IL-6 locus. Of these, 77 healthy controls and 87 CP patients were selected for measurement of plasma IL-6 by Luminex assay. The SHEsis program was used to analyze the genotyping data. For all comparisons; multiple testing on each individual SNP was corrected by the SNPSpD program.ResultsThere were no differences in allele or genotype frequencies between the overall CP patients and controls among the five genetic polymorphisms. However, subgroup analysis found significant sex-related differences in allele and genotype frequencies. Differences were found between spastic CP and controls in males for rs2069837; between CP with periventricular leukomalacia and controls in males for rs1800796 and rs2066992; and between term CP and controls in males for rs2069837. Plasma IL-6 levels were higher in CP patients than in the controls, and this difference was more robust in full-term male spastic CP patients. Furthermore, the genotype has an effect on IL-6 synthesis.ConclusionsThe influence of IL-6 gene polymorphisms on IL-6 synthesis and the susceptibility to CP is related to sex and gestational age.

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“…In patients with type 2 diabetes, rs1800795 SNP of the IL-6 gene is significantly related to increased risk of cardiovascular disease [15]. In addition, rs1800795 SNP of the IL-6 gene is related with autoimmune diseases such as systemic lupus erythematosus [16], systemic sclerosis [17], and autoimmune thyroid disease [18]. …”

Section: Introductionmentioning

confidence: 99%

Promoter Polymorphism (-174, G/C) of Interleukin-6 and Arterial Thromboembolic Events: A Meta-Analysis

2016

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BackgroundIschemic stroke and myocardial infarction are fatal diseases and are among the top 10 causes of death in Korea, including arterial thromboembolic events. Many previous studies have described the function of interleukin-6 (IL-6) in arterial thromboembolic events and the association between promoter single-nucleotide polymorphism (SNP) (rs1800795; −174, G/C) of the IL-6 gene. However, these results were controversial. Therefore, we performed a meta-analysis to more precisely assess the association between the SNP of the IL-6 gene and susceptibility to arterial thromboembolic events.Material/MethodsWe used PubMed, Embase, Google Scholar, and Korean Studies Information Service System (KISS) electronic databases. Comprehensive Meta-analysis software (Corporation, NJ) was used to evaluate the relationship between rs1800795 SNP of IL-6 gene and risk of arterial thromboembolic events. Odds ratio (OR), 95% confidence interval (CI), and P value were also calculated. The 13 eligible studies were analyzed in the meta-analysis.ResultsThe present meta-analysis found that rs1800795 SNP of IL-6 gene is not significantly associated with susceptibility to arterial thromboembolic events (C allele vs. G allele, OR=1.04, 95% CI=0.91–1.19, P=0.619; CC vs. CG+GG, OR=1.09, 95% CI=0.91–1.31, P=0.364; CC+CG vs. GG, OR=0.97, 95% CI=0.78–1.21, P=0.763, respectively), and the SNP of IL-6 gene also did not show any significant association with ischemic stroke or myocardial infarction (P>0.05 in each model).ConclusionsWe found that rs1800795 SNP of IL-6 gene was not related to arterial thromboembolic events. However, further study will be needed to confirm these results.

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Influence of the IL6 Gene in Susceptibility to Systemic Sclerosis

Abstract: Our results suggest that the IL6 gene may influence the development of SSc and its progression.

Cited by 37 publications

References 24 publications

Inflammatory Genes and Psychological Factors Predict Induced Shoulder Pain Phenotype

Inflammatory Genes and Psychological Factors Predict Induced Shoulder Pain Phenotype

The association between sex-related interleukin-6 gene polymorphisms and the risk for cerebral palsy

Promoter Polymorphism (-174, G/C) of Interleukin-6 and Arterial Thromboembolic Events: A Meta-Analysis

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