Clinical Rheumatology

, Volume 34, Issue 8, pp 1375–1382 | Cite as

Genetics of serum concentration of IL-6 and TNFα in systemic lupus erythematosus and rheumatoid arthritis: a candidate gene analysis

  • Joseph F. Solus
  • Cecilia P. Chung
  • Annette Oeser
  • Chun Li
  • Young Hee Rho
  • Kevin M. Bradley
  • Vivian K. Kawai
  • Jeffrey R. Smith
  • C. Michael Stein
Original Article


Elevated concentrations of inflammatory mediators are characteristic of autoimmune disease accompanied by chronic or recurrent inflammation. We examined the hypothesis that mediators of inflammation known to be elevated in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are associated with genetic polymorphism previously identified in studies of inflammatory disease. Serum interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFα) concentrations in patients with SLE (n = 117) or RA (n = 164) and in inflammatory disease-free control subjects (n = 172) were measured by multiplex ELISA. Candidate genes were chosen from studies of autoimmune and inflammatory disease. Genotypes were determined for 345 SNP markers in 75 genes. Association between serum analytes and single alleles was tested by linear regression. Polymorphisms in several genes were associated with IL-6 levels (including IL10, TYK2, and CD40L in SLE and DRB1, NOD2, and CSF1 in RA) or with TNFα levels (including TNFSF4 and CSF2 in SLE and PTPN2, DRB1, and NOD2 in RA). Some associations were shared between disease and control groups or between IL-6 and TNFα within a group. In conclusion, variation in genes implicated in disease pathology is associated with serum IL-6 or TNFα concentration. Some genetic associations are more apparent in healthy controls than in SLE or RA, suggesting dysregulation of the principal mediators of chronic inflammation in disease. Susceptibility genes may affect inflammatory response with variable effect on disease etiology.


Genes IL-6 Rheumatoid arthritis SNP Systemic lupus erythematosus TNFα 


Sources of funding

This study was supported by NIH grants HL65082, HL67964, GM07569, 2UL1 TR00044506, P60 AR056116, K23AR064768, the Vanderbilt Physician Scientist Development award, and the Dan May Chair in Medicine.

Conflict of interest

None of the authors has a conflict of interest related to this work.

Supplementary material

10067_2015_2881_MOESM1_ESM.pdf (182 kb)
Supplementary Table 1 (PDF 181 kb)
10067_2015_2881_MOESM2_ESM.pdf (162 kb)
Supplementary Table 2 (PDF 162 kb)


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Copyright information

© International League of Associations for Rheumatology (ILAR) 2015

Authors and Affiliations

  • Joseph F. Solus
    • 1
    • 2
  • Cecilia P. Chung
    • 1
  • Annette Oeser
    • 3
  • Chun Li
    • 4
  • Young Hee Rho
    • 1
    • 3
  • Kevin M. Bradley
    • 5
  • Vivian K. Kawai
    • 3
  • Jeffrey R. Smith
    • 5
  • C. Michael Stein
    • 1
    • 3
  1. 1.Division of RheumatologyVanderbilt UniversityNashvilleUSA
  2. 2.Division of Allergy, Pulmonary, and Critical Care MedicineVanderbilt UniversityNashvilleUSA
  3. 3.Division of Clinical PharmacologyVanderbilt UniversityNashvilleUSA
  4. 4.Department of BiostatisticsVanderbilt UniversityNashvilleUSA
  5. 5.Division of Genetic MedicineVanderbilt UniversityNashvilleUSA

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