Volume 3 Supplement 2

21st European Workshop for Rheumatology Research

Open Access

Association between TNF -308A and systemic lupus erythematosus in relation to HLA-DR3 and six microsatellite markers on the short arm of chromosome VI

  • MW van der Linden1, 2,
  • A van der Slik3,
  • E Pieterman2,
  • E Zanelli3,
  • MJ Giphart3,
  • FC Breedveld2,
  • RGJ Westendorp4 and
  • TWJ Huizinga2
Arthritis Research & Therapy20013(Suppl 2):P032


Received: 15 January 2001

Published: 26 January 2001

Allelic imbalance at polymorphic loci within the human HLA-DRB1 and TNF genes has been observed in association with increased susceptibility to systemic lupus erythematosus. We investigated whether the association of HLA-DRB1*0301 (HLA-DR3) and TNF-308A with SLE could be attributed to linkage to six polymorphic microsatellites between HLA-DRB1 and HLA-C. Ninety-one consecutive Caucasian patients with SLE and 253 controls (organ donors) were typed for HLA-DRB1, D6S1014, D6S273, TNFa, MIB, C-1-2-5 and C-1-3-2 and for TNF promoter polymorphisms. Independent contribution of alleles to disease susceptibility was estimated by crosstabulation and multivariate regression.


Carriership of TNF-308A was associated with susceptibility to SLE (odds ratio [95% confidence interval], 3.70 [2.24-6.11]). This remained present after stratification on carriership of HLA-DR3 (pooled odds ratio, 2.53 [1.37-4.70]). Stratification further revealed a possible association of carriership of C-1-2-5*192 with protection from SLE beyond the effects of HLA-DR3 and TNF-308A. Gene dose effect was observed for -308A only (homozygotes, 7.75[3.01-20.0], heterozygotes, 3.15[1.85-5.37]). In multivariate analysis, the association between HLA-DR3, TNF-308A, and C-1-2-5*192 remained independently associated with susceptibility to SLE (2.58 [1.29-5.18], 2.76 [1.43-5.31], and 0.26[0.10-0.66], repsectively).


An association of carriership of TNF-308A with susceptibility to SLE can not be attributed to linkage to HLA-DR3, nor to other polymorphic markers in the vicinity of the TNF gene. Further loci that are independently associated with SLE might be located in the vicinity of marker C-1-2-5.

Authors’ Affiliations

Department of Clinical Epidemiology, Leiden University Medical Center
Department of Rheumatology, Leiden University Medical Center
Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center
Department of General Internal Medicine, Leiden University Medical Center


© BioMed Central Ltd 2001