Association of the IL-6R Gene Polymorphic Variant Rs2228145(C>A) with IL-6 Gene Polymorphisms in a Healthy Cohort of Turkish Population

Overview

Journal Genes Immun

Date 2022 Mar 26

PMID 35338260

Authors

Lutfiye Karcioglu Batur

Serdar Savas

Erhan Girgin

Nezih Hekim

Affiliations

Soon will be listed here.

Abstract

The main aim of this study was to investigate the relationship of the carriership of rs2228145 allelic variations of IL-6R with two other allelic variations in IL-6 gene at rs1800795 and rs1800796 loci and with the laboratory data of a healthy cohort of the Turkish population. The data of 121 healthy Turkish subjects (aged 12-84 years) including the past diseases, comorbidities were collected. The laboratory parameters were compared by the frequency of alleles of rs2228145 (C>A). The possible association of polymorphism at rs2228145 locus with the age, gender, and body mass index (BMI) and the frequencies of alleles of rs1800795 and rs1800796 polymorphisms were evaluated. The majority of the subjects had allele A at rs2228145 locus and allele G at rs1800796 locus. The number of white blood cells, platelets, neutrophils and monocytes were significantly higher in the subjects with allele C than those with allele A at rs2228145 locus (P < 0.05). The concentrations of total and direct bilirubin, iron, Sex Hormone Binding Globulin (SHBG) and folic acid of the subjects with allele C were significantly lower than those with allele A (P < 0.05). The uric acid and fasting insulin levels were higher in the subjects with allele C compared with those allele A (P = 0.04). The diversities of the hematological parameters, laboratory findings of liver function tests and renal panel and hormone levels may be explained by the variants of rs2228145 locus at IL-6R gene among healthy Turkish individuals.

Citing Articles

IL6 receptor inhibitors: exploring the therapeutic potential across multiple diseases through drug target Mendelian randomization.

Fu C, Wang L, Cai W Front Immunol. 2024; 15:1452849.

PMID: 39229261 PMC: 11368790. DOI: 10.3389/fimmu.2024.1452849.

GlycA and CRP Are Genetically Correlated: Insight into the Genetic Architecture of Inflammageing.

Kasher M, Freidin M, Williams F, Livshits G, Charge Inflammation Working Group Biomolecules. 2024; 14(5).

PMID: 38785970 PMC: 11117775. DOI: 10.3390/biom14050563.

Association of Polymorphisms of IL-6 Pathway Genes (IL6, IL6R and IL6ST) with COVID-19 Severity in an Amazonian Population.

Rodrigues F, da Silva R, Dos Santos E, de Brito M, da Silva A, de Meira Leite M Viruses. 2023; 15(5).

PMID: 37243282 PMC: 10220739. DOI: 10.3390/v15051197.

The effect of interleukin-6 signaling on severe malaria: A Mendelian randomization analysis.

Hamilton F, Mitchell R, Constantinescu A, Hughes D, Cunnington A, Ghazal P Int J Infect Dis. 2023; 129:251-259.

PMID: 36801374 PMC: 10728776. DOI: 10.1016/j.ijid.2023.02.008.

Review of Medical Studies on COVID-19 During the Pandemic Period.

Aksakal A, Kerget B Eurasian J Med. 2023; 54(Suppl1):154-158.

PMID: 36655460 PMC: 11163338. DOI: 10.5152/eurasianjmed.2022.22336.

References

Ruggeri R, Barresi G, Sciacchitano S, Trimarchi F, Benvenga S, Trovato M . Immunoexpression of the CD30 ligand/CD30 and IL-6/IL-6R signals in thyroid autoimmune diseases. Histol Histopathol. 2005; 21(3):249-56. DOI: 10.14670/HH-21.249. View

Zhou L, Zheng Y, Tian T, Liu K, Wang M, Lin S . Associations of interleukin-6 gene polymorphisms with cancer risk: Evidence based on 49,408 cancer cases and 61,790 controls. Gene. 2018; 670:136-147. DOI: 10.1016/j.gene.2018.05.104. View

Kerget F, Kerget B . Frequency of Interleukin-6 rs1800795 (-174G/C) and rs1800797 (-597G/A) Polymorphisms in COVID-19 Patients in Turkey Who Develop Macrophage Activation Syndrome. Jpn J Infect Dis. 2021; 74(6):543-548. DOI: 10.7883/yoken.JJID.2021.046. View

Trovato M, Sciacchitano S, Facciola A, Valenti A, Visalli G, Di Pietro A . Interleukin‑6 signalling as a valuable cornerstone for molecular medicine (Review). Int J Mol Med. 2021; 47(6). PMC: 8057292. DOI: 10.3892/ijmm.2021.4940. View

Yamasaki K, Taga T, Hirata Y, Yawata H, Kawanishi Y, Seed B . Cloning and expression of the human interleukin-6 (BSF-2/IFN beta 2) receptor. Science. 1988; 241(4867):825-8. DOI: 10.1126/science.3136546. View

Hibi M, Murakami M, Saito M, Hirano T, Taga T, Kishimoto T . Molecular cloning and expression of an IL-6 signal transducer, gp130. Cell. 1990; 63(6):1149-57. DOI: 10.1016/0092-8674(90)90411-7. View

Murakami M, Kamimura D, Hirano T . Pleiotropy and Specificity: Insights from the Interleukin 6 Family of Cytokines. Immunity. 2019; 50(4):812-831. DOI: 10.1016/j.immuni.2019.03.027. View

Salvi R, Patankar P . Emerging pharmacotherapies for COVID-19. Biomed Pharmacother. 2020; 128:110267. PMC: 7221369. DOI: 10.1016/j.biopha.2020.110267. View

Garbers C, Rose-John S . Dissecting Interleukin-6 Classic- and Trans-Signaling in Inflammation and Cancer. Methods Mol Biol. 2018; 1725:127-140. DOI: 10.1007/978-1-4939-7568-6_11. View

10.

Kraakman M, Kammoun H, Allen T, Deswaerte V, Henstridge D, Estevez E . Blocking IL-6 trans-signaling prevents high-fat diet-induced adipose tissue macrophage recruitment but does not improve insulin resistance. Cell Metab. 2015; 21(3):403-16. DOI: 10.1016/j.cmet.2015.02.006. View

11.

Timper K, Denson J, Steculorum S, Heilinger C, Engstrom-Ruud L, Wunderlich C . IL-6 Improves Energy and Glucose Homeostasis in Obesity via Enhanced Central IL-6 trans-Signaling. Cell Rep. 2017; 19(2):267-280. DOI: 10.1016/j.celrep.2017.03.043. View

12.

Scheller J, Chalaris A, Schmidt-Arras D, Rose-John S . The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta. 2011; 1813(5):878-88. DOI: 10.1016/j.bbamcr.2011.01.034. View

13.

Abbasifard M, Khorramdelazad H . The bio-mission of interleukin-6 in the pathogenesis of COVID-19: A brief look at potential therapeutic tactics. Life Sci. 2020; 257:118097. PMC: 7361088. DOI: 10.1016/j.lfs.2020.118097. View

14.

Sehgal P, Zilberstein A, Ruggieri R, May L, A Ferguson-Smith , Slate D . Human chromosome 7 carries the beta 2 interferon gene. Proc Natl Acad Sci U S A. 1986; 83(14):5219-22. PMC: 323922. DOI: 10.1073/pnas.83.14.5219. View

15.

Sutherland G, Baker E, Callen D, Hyland V, Wong G, Clark S . Interleukin 4 is at 5q31 and interleukin 6 is at 7p15. Hum Genet. 1988; 79(4):335-7. DOI: 10.1007/BF00282171. View

16.

Garbers C, Heink S, Korn T, Rose-John S . Interleukin-6: designing specific therapeutics for a complex cytokine. Nat Rev Drug Discov. 2018; 17(6):395-412. DOI: 10.1038/nrd.2018.45. View

17.

Harrison S, Smith A, Jones G, Swerdlow D, Rampuri R, Bown M . Interleukin-6 receptor pathways in abdominal aortic aneurysm. Eur Heart J. 2012; 34(48):3707-16. PMC: 3869968. DOI: 10.1093/eurheartj/ehs354. View

18.

Ferreira R, Freitag D, Cutler A, Howson J, Rainbow D, Smyth D . Functional IL6R 358Ala allele impairs classical IL-6 receptor signaling and influences risk of diverse inflammatory diseases. PLoS Genet. 2013; 9(4):e1003444. PMC: 3617094. DOI: 10.1371/journal.pgen.1003444. View

19.

Wosiski-Kuhn M, Robinson M, Strupe J, Arounleut P, Martin M, Caress J . IL6 receptorAla variant and trans-signaling are disease modifiers in amyotrophic lateral sclerosis. Neurol Neuroimmunol Neuroinflamm. 2019; 6(6):e631. PMC: 6865852. DOI: 10.1212/NXI.0000000000000631. View

20.

Sarwar N, Butterworth A, Freitag D, Gregson J, Willeit P, Gorman D . Interleukin-6 receptor pathways in coronary heart disease: a collaborative meta-analysis of 82 studies. Lancet. 2012; 379(9822):1205-13. PMC: 3316940. DOI: 10.1016/S0140-6736(11)61931-4. View