ORIGINAL ARTICLE Interleukin-1 gene cluster and IL-1 receptor polymorphisms in Iranian patients with systemic lupus erythematosus Zahra Tahmasebi • Mahmoud Akbarian • Sedigheh Mirkazemi • Abtin Shahlaee • Zahra Alizadeh • Ali Akbar Amirzargar • Ahmad Reza Jamshidi • Shima Ghoroghi • Shiva Poursani • Keramat Nourijelyani • Mahdi Mahmoudi Received: 19 December 2012 / Accepted: 16 May 2013 Ó Springer-Verlag Berlin Heidelberg 2013 Abstract Systemic lupus erythematosus (SLE) is a sys- temic autoimmune disease of unknown etiology with a complex pathogenesis involving multiple genetic and envi- ronmental contributions. Single-nucleotide polymorphisms (SNPs) in cytokine genes are associated with higher or lower cytokine activity, which can alter the susceptibility to certain diseases or their clinical outcomes. We investigated SNPs of the IL-1 family in Iranian SLE patients and normal indi- viduals. We obtained blood samples from 207 SLE patients and 213 healthy controls. Cytokine genotyping was per- formed by polymerase chain reaction with sequence-specific primers. The following SNPs were assessed: IL-1A rs1800587, IL-1B rs16944 and rs1143634, IL-1R1 rs2234650 and IL-1RN rs315952. The frequency of the IL- 1RN rs315952 CT genotype was significantly lower among patients with SLE compared with healthy controls (OR = 0.63, 95 % CI = 0.42–0.95; P \ 0.05 relative to reference genotype and OR = 0.62, CI = 0.42–0.93; P \ 0.05 relative to homozygous genotypes). For all other studied alleles and genotypes, there were no significant differences concerning genotype frequencies between patients and controls. A significant increase in IL-1RN rs315952 T allele frequency was noted in patients with a hematologic manifestation (OR = 1.75; 95 % CI = 1.07–2.84; P = 0.033). Polymorphism in IL-1RN rs315952 was significantly associated with SLE in Iranian patients, rs315952CT genotype being a protective factor. We found that IL-1RN rs315952 T allele frequency was significantly higher in patients with hematologic manifestations. Varia- tion at this locus may affect IL-1 receptor antagonist activity, supporting the hypothesis that altered or imbalanced IL1 production may affect the risk of developing SLE. Keywords Systemic lupus erythematosus Á Interleukin-1 gene cluster Á Single-nucleotide polymorphism Introduction Systemic lupus erythematosus (SLE) is an autoimmune disease which is portrayed as multi-systemic inflammation of various tissues and the production of antibodies to components of the cell nucleus with a broad spectrum of clinical presentations. Thus, the disease is characterized by high titers of autoantibodies against nuclear antigens and inflammatory manifestations such as nephritis, vasculitis, arthritis and lymphadenopathy. The elevated levels of various cytokines have also been found in SLE patients, so that they have been considered as essential elements in the etiopathology of disease [1]. The exact etiology of SLE is unknown; however, the contribution of complex pathogenesis mechanisms involv- ing multiple environmental factors is attributed to the Z. Tahmasebi Á M. Akbarian Á S. Mirkazemi Á A. Shahlaee Á Z. Alizadeh Á A. R. Jamshidi Á S. Ghoroghi Á S. Poursani Á M. Mahmoudi (&) Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Kargar Ave., PO-BOX: 1411713137, Tehran, Iran e-mail: mahmoudim@tums.ac.ir A. Shahlaee Students’ Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran A. A. Amirzargar Molecular Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran K. Nourijelyani Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran 123 Rheumatol Int DOI 10.1007/s00296-013-2784-2