 |
| Full Paper |
| Six microsatellite markers on the short arm of chromosome 6 in relation to HLA-DR3 and TNF-308A in systemic lupus erythematosus |
|
| M W van der Linden1,2,a, A R van der Slik3, E Zanelli3, M J Giphart3, E Pieterman2, G M Th Schreuder3, R G J Westendorp4 and T W J Huizinga2 |
|
1Department of Clinical Epidemiology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands
2Department of Rheumatology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands
3Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands
4Department of General Internal Medicine, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands
|
|
Correspondence to: Dr T W J Huizinga, Department of Rheumatology, Building 1, C4-R, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. E-mail: T.W.J.Huizinga.reuma@lumc.nl
| |
aMW van der Linden is supported by a grant of the Dutch Organization for Scientific Research (N.W.O.), grant no. 904-61-110. |
|
| Abstract |
| Differences in allelic distribution at loci surrounding the human HLA-DRB1 and tumor necrosis factor (TNF) genes have been observed in association with systemic lupus erythematosus (SLE). We investigated whether the association of HLA-DRB1*0301 (HLA-DR3) and TNF-308A with SLE could be attributed to polymorphic markers in the chromosomal region encompassed by HLA-DRB1 and HLA-C. Ninety-one consecutive Caucasian patients with SLE and 253 controls (organ donors) were typed for HLA-DRB1, microsatellites D6S1014, D6S273, TNFa, MIB, C1_2_5, and C1_3_2 and the single nucleotide polymorphism at position -308 in the promoter of TNF. The independent contribution of alleles to disease susceptibility was estimated by cross-tabulation and multivariate logistic regression. Possession 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 possession of HLA-DR3 (pooled odds ratio, 2.53 [1.37-4.70]). Stratification revealed a possible association of possession of C1_2_5*192 with protection from SLE beyond the effects of HLA-DR3 and TNF-308A. A gene dosage effect was observed for -308A only (homozygotes, 7.75 [3.01-20.0], heterozygotes, 3.15 [1.85-5.37]). In multivariate analysis, possession of HLA-DR3, TNF-308A, and C1_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], respectively). The association of possession of TNF-308A with susceptibility to SLE cannot be attributed to linkage to HLA-DR3 alone, nor to other polymorphic markers in the vicinity of the TNF gene. Further loci that are independently associated with SLE might be in the vicinity of marker C1_2_5. Genes and Immunity (2001) 2, 373-380. |
|
| Keywords |
| HLA-DRB1; TNF; genetics; susceptibility; systemic lupus erythematosus |
|
|
|
|
| Received 8 February 2001; revised 6 August 2001; accepted 6 August 2001 |
|
| November 2001, Volume 2, Number 7, Pages 373-380 |
| Table of contents Previous Abstract Next Full text PDF |
|
