Interleukin-10 gene polymorphisms are associated with the SLICC/ACR Damage Index in systemic lupus erythematosus

Abstract

Objective. Overproduction of interleukin-10 (IL-10) is a pivotal feature in the pathophysiology of systemic lupus erythematosus (SLE). We examined the IL10 genotype of Korean patients with SLE and normal controls to determine whether associations exist between the pattern of inherited IL10 genes and SLE susceptibility or the SLICC/ACR Damage Index (SDI). Methods. A total of 350 Korean SLE patients and 330 healthy subjects were enrolled. Direct DNA sequencing and primer extension procedures were employed. Logistic regression analyses were performed to examine the genetic association with SLE and SDI. Results. Eight sequence variants were identified by direct DNA sequencing in 24 Korean individuals. Five of the polymorphisms were selected for larger scale genotyping (n = 680) by considering their allele frequencies, haplotype-tagging status and linkage disequilibrium coefficients among polymorphisms. Haplotypes and allele distributions of the IL10 polymorphisms did not differ significantly between SLE patients and controls. Among identified SNPs, the rare C allele of IL10-592A -> C was significantly associated with the SDI among SLE patients in the following three alternative models: codominant (P = 0.007, odds ratio = 1.70), dominant (P = 0.02, odds ratio = 1.85) and recessive (P = 0.05, odds ratio = 2.25). Similarly, IL10+955T -> G and IL10-ht2 were significantly associated with the SDI in the codominant and dominant models. Conclusion. IL10 polymorphisms are not associated with disease susceptibility in Korean patients with SLE. However, IL10-592A -> C, IL10+955T -> G and IL10-ht2 are significantly associated with the SDI, suggesting that IL10-592C, IL10+955G and IL10-ht2 accelerate the damage induced by SLE.