Clinical implications of IL-10 promoter polymorphisms on disease susceptibility in Indian SLE patients

Abstract

Single nucleotide polymorphisms in cytokine genes including interleukin-10 have been described to play a vital role in the overall pathogenesis of systemic lupus erythematosus. However, due to a lack of evidence from the Indian population, this study was conducted to analyse the possible influence of interleukin-10 promoter polymorphisms over the disease susceptibility, serum interleukin-10 level and clinical manifestations of the disease in Indian systemic lupus erythematosus patients. In total, 200 systemic lupus erythematosus patients and 201 controls were recruited under this study. Genotyping of interleukin-10 (−1082A/G; −819T/C and −592C/A) polymorphisms was done by direct DNA sequencing and polymerase chain reaction-restriction fragment length polymorphism methods respectively. Serum interleukin-10 levels were measured by multiplex assay. Interleukin-10 −1082G and −592A allele frequencies were significantly increased in systemic lupus erythematosus patients (corrected p value <0.05). Also, combined −1082AG+GG, −819TC+CC and −592CA+AA genotype frequencies were significantly increased in the patient group. A higher trend of association between −1082AG+GG genotype frequency was observed in patients with serositis (odds ratio = 2.7, p = 0.0233, corrected p value = 0.2097). Serum interleukin-10 levels were significantly higher in systemic lupus erythematosus patients (4.3 ± 3.1 pg/ml) than controls (2.6 ± 1.4 pg/ml) ( p < 0.0001). Furthermore, interleukin-10 levels were positively correlated with disease activity ( p = 0.39, p < 0.0001). The frequency of the GCA (−1082, −819, −592) haplotype was significantly higher in systemic lupus erythematosus patients (10.6%) than controls (1.6%) (odds ratio = 5.4, p = 0.0330). Moreover, ACC, GCC and GCA haplotypes were found to be strongly associated with serositis. However, the frequency of the ACC haplotype was significantly higher in patients with neurologic involvement (odds ratio = 14.9, corrected p value <0.001). Thus, interleukin-10 promoter polymorphisms suggest they have a proactive role in increased susceptibility to the disease among Indian systemic lupus erythematosus patients.