Anti-IL-6 receptor antibody treatment for severe COVID-19 and the potential implication of IL-6 gene polymorphisms in novel coronavirus pneumonia

Ulhaq, Zulvikar Syambani; Soraya, Gita Vita

doi:10.1016/j.medcli.2020.07.002

Cited by 49 publications

(25 citation statements)

References 31 publications

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“…14 A very recent meta-analysis reported a relation between the IL6 gene polymorphism and predisposition as well as disease severity of pneumonia, suggested the carrier status of IL6 allele with higher IL-6 production and pneumonia severity. 57 However, in the present study, we could not nd a signi cant correlation between the frequencies of rs1800796/rs1800795 and rs2228145 polymorphisms in IL-6 and IL-6R genes, probably due to the variations among the genetic immune pro ling of populations.…”

Section: Discussioncontrasting

confidence: 82%

Correlations of IL-6, IL-6R, IL-10 and IL-17 gene polymorphisms with the prevalence of COVID-2019 infection and its mortality rate 

Batur

Hekim

2020

Preprint

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The pathogenesis of COVID-19 implicates a potent inflammatory response resulting in cytokine storm. We aimed to evaluate association between polymorphisms in IL-6 gene at rs1800796/rs1800795, IL-6R at rs2228145, IL-10 at rs1800896 and rs1800871, IL-17 at rs2275913 and rs76378, and the prevalence (per million) and mortality rates (per million) of COVID-19 among populations of China, Japan, India, Iran, Spain, Italy, Mexico, Netherlands, Sweden, Turkey, Finland, Brazil, Czechia, Russia, Poland. AG and GG genotypes of rs2275913 in IL-17A was found to be correlated with prevalence and mortality rates, especially in Spain and Brazil populations (p<0.05) while TT genotype of rs763780 in IL-17F was not dependent on the high frequencies in all populations. However, the polymorphisms in IL-6, IL-6R and IL-10 appear not to be correlated with prevalence and mortality rates. The variations in the prevalence of COVID-19 and its mortality rates among countries may be explained by cytokine storm differed by the polymorphisms of rs2275913 locus in IL-17A gene. However, the prevalence of infection differs from severity of COVID-19, based on many factors such as public awareness, behaviors and antiviral policy of countries. Yet, the severity of disease induced by viral infection might be associated with genetic host factors including immune profiling.

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Section: Discussioncontrasting

confidence: 82%

Correlations of IL-6, IL-6R, IL-10 and IL-17 gene polymorphisms with the prevalence of COVID-2019 infection and its mortality rate 

Batur

Hekim

2020

Preprint

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“…The I 2 values indicated no (0-24.9%), low (25-49.9%), moderate (50-74.9%) or high (75-100%) heterogeneity. The random-effect model (REM) was used if heterogeneity existed; otherwise, the fixed-effect model (FEM) was used 250,[276][277][278][279][280][281][282][283][284][285][286][287] . Subgroup analysis was stratified by type of disease and ethnicity or racial descent.…”

Section: Methodsmentioning

confidence: 99%

The role of IL-6-174 G/C polymorphism and intraocular IL-6 levels in the pathogenesis of ocular diseases: a systematic review and meta-analysis

Ulhaq

Soraya

Budu

et al. 2020

Sci Rep

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Interleukin-6 (IL-6) is one of the key regulators behind the inflammatory and pathological process associated with ophthalmic diseases. The role of IL-6-174 G/C polymorphism as well as intraocular IL-6 levels among various eye disease patients differ across studies and has not been systematically reviewed. Thus, this study aims to provide a summary to understand the relationship between IL-6 and ophthalmic disease. In total, 8,252 and 11,014 subjects for IL-6-174 G/C and intraocular levels of IL-6, respectively, were retrieved from PubMed, Scopus and Web of Science. No association was found between IL-6-174 G/C polymorphisms with ocular diseases. Subgroup analyses revealed a suggestive association between the GC genotype of IL-6-174 G/C with proliferative diabetic retinopathy (PDR). Further, the level of intraocular IL-6 among ocular disease patients in general was found to be higher than the control group [standardized mean difference (SMD) = 1.41, 95% confidence interval (CI) 1.24–1.58, P < 0.00001]. Closer examination through subgroup analyses yielded similar results in several ocular diseases. This study thus indicates that the IL-6-174 G/C polymorphism does not predispose patients to ocular disease, although the GC genotype is likely to be a genetic biomarker for PDR. Moreover, intraocular IL-6 concentrations are related to the specific manifestations of the ophthalmic diseases. Further studies with larger sample sizes are warranted to confirm this conclusion.

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“…Meta-analysis for each gene polymorphism was performed for two or more studies, as previously described [ 3 , 4 , 5 , 6 , 22 , 23 , 24 , 25 ]. Genotypic frequency of GPER gene polymorphism was tested for deviation from the Hardy–Weinberg equilibrium (HWE) in the control subjects if HWE was not reported.…”

Section: Methodsmentioning

confidence: 99%

“…Genotypic frequency of GPER gene polymorphism was tested for deviation from the Hardy–Weinberg equilibrium (HWE) in the control subjects if HWE was not reported. The genetic association was examined using different genetic models, including allelic (a vs. A), recessive (aa vs. Aa + AA), dominant (aa + Aa vs. AA), over dominant (Aa vs. aa + AA), homozygous (aa vs. AA), and heterozygous (Aa vs. AA) models [ 5 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. The associations between GPER gene polymorphisms or GPER expression levels with cancer predisposition and progression were calculated by the pooled odds ratio (OR) and 95% confidence interval (CI).…”

Section: Methodsmentioning

confidence: 99%

Association between GPER gene polymorphisms and GPER expression levels with cancer predisposition and progression

Ulhaq

Soraya

Milliana

et al. 2021

Heliyon

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Estrogen is a female sex steroid hormone that plays a significant role in physiological functions. Evidence suggests that estrogen-signaling pathways are closely linked to cancer development and progression. The novel G protein-coupled estrogen receptor (GPER or GPR30) has been shown to influence cancer predisposition and progression, although results of related studies remain equivocal. Thus, this meta-analysis aimed to estimate the relationship between GPER gene polymorphisms and GPER expression levels, with cancer predisposition and progression. The pooled results showed that two GPER polymorphisms, rs3808350 and rs3808351, were significantly associated with cancer predisposition, especially in the Asian population, but no significant association was detected for rs11544331. In parallel, we also found that cancer aggressiveness and progression correlated with rs3808351 and GPER expression in cancerous tissues. Altogether, our findings suggest that GPER plays a pivotal role in cancer pathogenesis and progression. We suggest that rs3808350 and rs3808351 may be used as a prospective biomarker for cancer screening; while rs3808351 and GPER expression can be used to examine the prognosis of patients with cancer. Further biological studies are warranted to confirm our findings.

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Anti-IL-6 receptor antibody treatment for severe COVID-19 and the potential implication of IL-6 gene polymorphisms in novel coronavirus pneumonia

Cited by 49 publications

References 31 publications

Correlations of IL-6, IL-6R, IL-10 and IL-17 gene polymorphisms with the prevalence of COVID-2019 infection and its mortality rate

Correlations of IL-6, IL-6R, IL-10 and IL-17 gene polymorphisms with the prevalence of COVID-2019 infection and its mortality rate

The role of IL-6-174 G/C polymorphism and intraocular IL-6 levels in the pathogenesis of ocular diseases: a systematic review and meta-analysis

Association between GPER gene polymorphisms and GPER expression levels with cancer predisposition and progression

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Anti-IL-6 receptor antibody treatment for severe COVID-19 and the potential implication of IL-6 gene polymorphisms in novel coronavirus pneumonia

Cited by 49 publications

References 31 publications

Correlations of IL-6, IL-6R, IL-10 and IL-17 gene polymorphisms with the prevalence of COVID-2019 infection and its mortality rate&nbsp;

Correlations of IL-6, IL-6R, IL-10 and IL-17 gene polymorphisms with the prevalence of COVID-2019 infection and its mortality rate&nbsp;

The role of IL-6-174 G/C polymorphism and intraocular IL-6 levels in the pathogenesis of ocular diseases: a systematic review and meta-analysis

Association between GPER gene polymorphisms and GPER expression levels with cancer predisposition and progression

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Correlations of IL-6, IL-6R, IL-10 and IL-17 gene polymorphisms with the prevalence of COVID-2019 infection and its mortality rate

Correlations of IL-6, IL-6R, IL-10 and IL-17 gene polymorphisms with the prevalence of COVID-2019 infection and its mortality rate