Impact of functional IL-18 polymorphisms on genetic predisposition and diverse clinical manifestations of the disease in Indian SLE patients

Abstract

Several studies have demonstrated associations between interleukin-18 polymorphisms and risk of systemic lupus erythematosus in different populations except one of Indian origin. We therefore investigated for the influence of interleukin-18 (-1297T/C, -607A/C, -137G/C; + 105A/C) polymorphisms on genetic susceptibility and clinical expression of the disease in Indian systemic lupus erythematosus patients. A total of 200 systemic lupus erythematosus patients and 201 controls were recruited. Genotyping of interleukin-18 polymorphisms were performed by polymerase chain reaction-restriction fragment length polymorphism. Serum interleukin-18 levels were measured by enzyme-linked immunosorbent assay. Interleukin-18 (-1297T/C; -137G/C) polymorphisms showed significant association with genetic susceptibility to the disease in our systemic lupus erythematosus cohort. Stratification analysis revealed -1297CC and -1297C associated with renal involvement (odds ratio = 3.4, correcting p value = 0.0207), (odds ratio = 2.0, correcting p value = 0.0054) respectively. Additionally, -1297C allele frequency was significantly increased in patients with anti-nucleosome antibody (odds ratio = 2.1, correcting p value = 0.0301). Haplotype analysis showed CC haplotype strongly associated with serositis (odds ratio = 9.1, correcting p values = 0.0009) and neurologic involvement (odds ratio = 9.3, correcting p value = 0.0018). We reported a 2.7-fold increase in serum interleukin-18 levels in patients (511.5 ± 242.3 pg/ml) compared to controls (189.4 ± 80.8 pg/ml) ( p < 0.0001). Furthermore, interleukin-18 levels were positively correlated with disease activity ( r = 0.548, p = 0.0001) and renal involvement in the patients with lupus nephritis ( r = 0.569, p < 0.0001). In summary, interleukin-18 polymorphisms elucidated in this study appear to confer genetic susceptibility to the disease and are associated with renal, serositis and neurologic involvement in Indian systemic lupus erythematosus patients.