Interleukin-10 promoter microsatellite polymorphisms in systemic lupus erythematosus: association with the anti-Sm immune response.
OBJECTIVE
Overproduction of interleukin-10 (IL-10) is a pivotal feature in the pathophysiology of systemic lupus erythematosus (SLE). In vitro IL-10 secretion has previously been related to haplotypes of the IL-10 promoter microsatellite polymorphisms IL10.R and IL10.G. Published data concerning the association of IL10.G alleles with susceptibility to SLE are inconsistent in different ethnic populations. We analysed the association of IL-10 promoter microsatellite polymorphisms with disease susceptibility and manifestations in German Caucasian patients with SLE.


METHODS
Two hundred and ten (210) SLE patients fulfilling the 1997 revised ACR criteria and 158 ethnically, age- and sex-matched healthy controls were genotyped for the IL-10 promoter microsatellite polymorphisms by fragment length analysis. Haplotypes were reconstructed using a Bayesian coalescent theory-based method with PHASE software. Allele and haplotype distributions were compared between patients and controls and between subgroups of patients with different clinical and immunopathological findings.


RESULTS
In the study population no significant associations of individual IL10.R and G alleles or their haplotypes with susceptibility to SLE or major clinical manifestations were observed. By contrast, alleles G14 and G15 and haplotypes R2-G14 and R2-G15 were significantly over-represented in anti-Sm antibody-positive patients.


CONCLUSIONS
The IL-10 promoter microsatellite polymorphisms and their haplotypes do not constitute a major risk factor for SLE in German Caucasians. However, the identification of genetic markers such as the IL-10 high-response haplotype R2-G14 predisposing for the production of anti-Sm antibodies may help to elucidate the conditions that lead to the development of SLE.
Medizinische Klinik, Universitätsklinikum Münster, Germany. h.schotte@uni-muenster.de
H
H
Schotte
M
M
Gaubitz
P
P
Willeke
N
N
Tidow
G
G
Assmann
W
W
Domschke
B
B
Schlüter
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens; D002648:Child; D002675:Child, Preschool; D005260:Female; D018628:Gene Dosage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D015810:Linkage Disequilibrium; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D017411:Ribonucleoproteins, Small Nuclear / Q000276:immunology*; D055517:snRNP Core Proteins
D001323:Autoantibodies; D001324:Autoantigens; D017411:Ribonucleoproteins, Small Nuclear; D055517:snRNP Core Proteins; D016753:Interleukin-10