Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders
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Interleukin-6

The IL6 gene encodes a cytokine that is involved in inflammation and the maturation of B cells. Genetic variations in this gene affect susceptibility to varous autoinflammatory and autoimmunologcal disorders including but not limited to type 1 diabetes, Kaposi sarcoma, brain vessel malformations, and juvenile arthritis.

Genetests:

Clinic Method Carrier testing
Turnaround 5 days
Specimen type genomic DNA
Clinic Method Massive parallel sequencing
Turnaround 25 days
Specimen type genomic DNA
Research Method Genomic sequencing of the entire coding region
Turnaround 25 days
Specimen type genomic DNA

Related Diseases:

Crohn disease-associated growth failure
IL6
Susceptibility to type 1 diabetes 01
PTPN22
Susceptibility to arteriovenous malformations of the brain
IL6
Susceptibility to Kaposi sarcoma
IL6
Systemic-onset juvenile idiopathic arthritis
IL6
LACC1
MIF

References:

1.

Illig T et al. (2004) Significant association of the interleukin-6 gene polymorphisms C-174G and A-598G with type 2 diabetes.

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2.

Mucida D et al. (2007) Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid.

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3.

Mora JR et al. (2006) Generation of gut-homing IgA-secreting B cells by intestinal dendritic cells.

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4.

Chen Y et. al. (2006) Interleukin-6 involvement in brain arteriovenous malformations.

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5.

Sawczenko A et al. (2005) Intestinal inflammation-induced growth retardation acts through IL-6 in rats and depends on the -174 IL-6 G/C polymorphism in children.

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6.

McLoughlin RM et al. (2005) IL-6 trans-signaling via STAT3 directs T cell infiltration in acute inflammation.

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7.

Seddon JM et al. (2005) Progression of age-related macular degeneration: prospective assessment of C-reactive protein, interleukin 6, and other cardiovascular biomarkers.

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8.

Liuzzi JP et al. (2005) Interleukin-6 regulates the zinc transporter Zip14 in liver and contributes to the hypozincemia of the acute-phase response.

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9.

Janssen SP et al. (2005) Interleukin-6 causes myocardial failure and skeletal muscle atrophy in rats.

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10.

Korn T et al. (2007) IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells.

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11.

Pawlikowska L et. al. (2004) Polymorphisms in genes involved in inflammatory and angiogenic pathways and the risk of hemorrhagic presentation of brain arteriovenous malformations.

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12.

Nemeth E et al. (2004) IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin.

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13.

Möhlig M et al. (2004) Body mass index and C-174G interleukin-6 promoter polymorphism interact in predicting type 2 diabetes.

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14.

Viereck V et al. (2003) Raloxifene concurrently stimulates osteoprotegerin and inhibits interleukin-6 production by human trabecular osteoblasts.

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15.

Kiecolt-Glaser JK et al. (2003) Chronic stress and age-related increases in the proinflammatory cytokine IL-6.

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16.

Boulanger MJ et al. (2003) Hexameric structure and assembly of the interleukin-6/IL-6 alpha-receptor/gp130 complex.

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17.

Chung HW et al. (2003) Association of interleukin-6 promoter variant with bone mineral density in pre-menopausal women.

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18.

Kristiansen OP et al. (2003) Association of a functional 17beta-estradiol sensitive IL6-174G/C promoter polymorphism with early-onset type 1 diabetes in females.

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19.

McFarland-Mancini MM et al. (2010) Differences in wound healing in mice with deficiency of IL-6 versus IL-6 receptor.

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20.

Zhang C et al. (2016) CD5 Binds to Interleukin-6 and Induces a Feed-Forward Loop with the Transcription Factor STAT3 in B Cells to Promote Cancer.

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21.

Zhang Q et al. (2015) Tet2 is required to resolve inflammation by recruiting Hdac2 to specifically repress IL-6.

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22.

Zenker S et al. (2014) A key regulatory role for Vav1 in controlling lipopolysaccharide endotoxemia via macrophage-derived IL-6.

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23.

Suthaus J et. al. (2012) HHV-8-encoded viral IL-6 collaborates with mouse IL-6 in the development of multicentric Castleman disease in mice.

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24.

Ellingsgaard H et al. (2011) Interleukin-6 enhances insulin secretion by increasing glucagon-like peptide-1 secretion from L cells and alpha cells.

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25.

Harker JA et al. (2011) Late interleukin-6 escalates T follicular helper cell responses and controls a chronic viral infection.

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26.

Xu Z et al. (2011) miR-365, a novel negative regulator of interleukin-6 gene expression, is cooperatively regulated by Sp1 and NF-kappaB.

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27.

Ghoreschi K et al. (2010) Generation of pathogenic T(H)17 cells in the absence of TGF-β signalling.

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28.

Powrie F et al. (2003) Immunology. Regulating the regulators.

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29.

Fairfax BP et al. (2010) An integrated expression phenotype mapping approach defines common variants in LEP, ALOX15 and CAPNS1 associated with induction of IL-6.

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30.

Sabio G et al. (2008) A stress signaling pathway in adipose tissue regulates hepatic insulin resistance.

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31.

Dai J et al. (2008) Adherence to the mediterranean diet is inversely associated with circulating interleukin-6 among middle-aged men: a twin study.

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32.

Ancrile B et al. (2007) Oncogenic Ras-induced secretion of IL6 is required for tumorigenesis.

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33.

Qi L et al. (2007) Interleukin-6 genetic variability and adiposity: associations in two prospective cohorts and systematic review in 26,944 individuals.

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34.

Meng F et al. (2008) Epigenetic regulation of microRNA-370 by interleukin-6 in malignant human cholangiocytes.

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35.

Naugler WE et al. (2007) Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production.

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36.

Lawrence T et al. (2007) Cancer. Sex, cytokines, and cancer.

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37.

Kawano M et al. (1988) Autocrine generation and requirement of BSF-2/IL-6 for human multiple myelomas.

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38.

Cressman DE et al. (1996) Liver failure and defective hepatocyte regeneration in interleukin-6-deficient mice.

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39.

Chung U et al. (1996) Association of interleukin-6 and hypoaldosteronism in patients with cancer.

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40.

Rooney M et. al. (1995) Inflammatory cytokine responses in juvenile chronic arthritis.

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41.

Weissenbach J et al. (1980) Two interferon mRNAs in human fibroblasts: in vitro translation and Escherichia coli cloning studies.

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42.

Sehgal PB et al. (1987) Human beta 2 interferon and B-cell differentiation factor BSF-2 are identical.

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43.

Hirano T et al. () Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin.

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44.

Ferguson-Smith AC et al. (1988) Regional localization of the interferon-beta 2/B-cell stimulatory factor 2/hepatocyte stimulating factor gene to human chromosome 7p15-p21.

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45.

Sutherland GR et al. (1988) Interleukin 4 is at 5q31 and interleukin 6 is at 7p15.

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46.

De Benedetti F et al. (1997) Interleukin 6 causes growth impairment in transgenic mice through a decrease in insulin-like growth factor-I. A model for stunted growth in children with chronic inflammation.

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47.

May LT et al. (1988) Synthesis and secretion of multiple forms of beta 2-interferon/B-cell differentiation factor 2/hepatocyte-stimulating factor by human fibroblasts and monocytes.

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48.

Sehgal PB et al. (1987) Rapid enhancement of beta 2-interferon/B-cell differentiation factor BSF-2 gene expression in human fibroblasts by diacylglycerols and the calcium ionophore A23187.

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49.

Zilberstein A et al. (1986) Structure and expression of cDNA and genes for human interferon-beta-2, a distinct species inducible by growth-stimulatory cytokines.

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50.

Sehgal PB et al. (1986) Human chromosome 7 carries the beta 2 interferon gene.

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51.

Bowcock AM et al. (1988) The human "interferon-beta 2/hepatocyte stimulating factor/interleukin-6" gene: DNA polymorphism studies and localization to chromosome 7p21.

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52.

Tosato G et al. (1988) Monocyte-derived human B-cell growth factor identified as interferon-beta 2 (BSF-2, IL-6).

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53.

Roodman GD et al. (1992) Interleukin 6. A potential autocrine/paracrine factor in Paget's disease of bone.

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54.

Santhanam U et al. (1991) Repression of the interleukin 6 gene promoter by p53 and the retinoblastoma susceptibility gene product.

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55.

Ota N et al. (2001) A nucleotide variant in the promoter region of the interleukin-6 gene associated with decreased bone mineral density.

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56.

Berthier MT et al. (2003) The interleukin 6-174G/C polymorphism is associated with indices of obesity in men.

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57.

Pasare C et al. (2003) Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells.

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58.

Ferrari SL et al. (2003) Two promoter polymorphisms regulating interleukin-6 gene expression are associated with circulating levels of C-reactive protein and markers of bone resorption in postmenopausal women.

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59.

de Groof F et al. (2002) Acute stress response in children with meningococcal sepsis: important differences in the growth hormone/insulin-like growth factor I axis between nonsurvivors and survivors.

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60.

Villuendas G et al. (2002) The -597 G>A and -174 G>C polymorphisms in the promoter of the IL-6 gene are associated with hyperandrogenism.

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61.

Kovalchuk AL et al. (2002) IL-6 transgenic mouse model for extraosseous plasmacytoma.

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62.

Funatsu H et al. (2002) Increased levels of vascular endothelial growth factor and interleukin-6 in the aqueous humor of diabetics with macular edema.

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63.

Venihaki M et al. (2001) Corticotropin-releasing hormone regulates IL-6 expression during inflammation.

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64.

Kane M et. al. (2011) Successful transmission of a retrovirus depends on the commensal microbiota.

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65.

Scheidt-Nave C et al. (2001) Serum interleukin 6 is a major predictor of bone loss in women specific to the first decade past menopause.

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66.

Chow D et. al. (2001) Structure of an extracellular gp130 cytokine receptor signaling complex.

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67.

Linker-Israeli M et al. (1999) Association of IL-6 gene alleles with systemic lupus erythematosus (SLE) and with elevated IL-6 expression.

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68.

Redwine L et al. (2000) Effects of sleep and sleep deprivation on interleukin-6, growth hormone, cortisol, and melatonin levels in humans.

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69.

Foster CB et. al. (2000) An IL6 promoter polymorphism is associated with a lifetime risk of development of Kaposi sarcoma in men infected with human immunodeficiency virus.

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70.

Ota N et al. (1999) Linkage of interleukin 6 locus to human osteopenia by sibling pair analysis.

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71.

Fernández-Real JM et al. (2000) Interleukin-6 gene polymorphism and lipid abnormalities in healthy subjects.

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72.

Fishman D et. al. (1998) The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis.

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Update: Aug. 14, 2020
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