Association of extended interleukin-10 promoter haplotypes with disease susceptibility and manifestations in German patients with systemic lupus erythematosus

Objectives Associations of interleukin-10 (IL-10) promoter single nucleotide polymorphisms (SNPs) and their haplotypes with systemic lupus erythematosus (SLE) are unclear. We extended the analysis of established proximal IL-10 promoter haplotypes to a more distal SNP with functional capacity. Methods Two hundred and ten German caucasian SLE patients fulfilling the ACR criteria and 160 ethnically, age and sex matched controls were genotyped for IL-10 −2849 G > A, −1082 A > G, −819 T > C and −592 C > A. Haplotypes were reconstructed via a mathematical model, then allele and haplotype distributions were compared between patients and controls and patients with different disease manifestations. Results We detected at −2849, −1082, −819 and −592 the four predominant haplotypes GGCC (22% in patients vs. 29% in controls), AGCC (24% vs. 21%), GACC (30% vs. 25%) and GATA (24% vs. 24%). GGCC was underrepresented in SLE patients, suggesting a protective effect (odds ratio (OR) 0.67, 95% confidence interval (CI) 0.48–0.94). AGCC was found significantly more frequently in patients with pathognomonic anti-dsDNA antibodies (26% vs. 15%; OR 1.98, 95% CI 1.04–3.75). As compared to patients with glomerulonephritis type V (WHO classification), the presumptive IL-10 high producer allele −2849 G was found significantly more often in patients with GN type III/IV (93% vs. 60%; OR 8.7, 95% CI 1.59–47.15). Conclusion Our data confirm that the complexity of the IL-10 promoter evokes the need for a meticulous analysis of its haplotypic structure in order to specify disease associations, particularly under functional aspects, thereby shedding light on the pathophysiology of SLE.