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  • Title: Polymorphisms in the interleukin 4, interleukin 13, and corresponding receptor genes are not associated with systemic sclerosis and do not influence gene expression.
    Author: Broen JC, Dieude P, Vonk MC, Beretta L, Carmona FD, Herrick A, Worthington J, Hunzelmann N, Riemekasten G, Kiener H, Scorza R, Simeon CP, Fonollosa V, Spanish Systemic Sclerosis Group, Carreira P, Ortego-Centeno N, Gonzalez-Gay MA, Airo' P, Coenen MJ, Tsang K, Aliprantis AO, Martin J, Allanore Y, Radstake TR.
    Journal: J Rheumatol; 2012 Jan; 39(1):112-8. PubMed ID: 22045834.
    Abstract:
    OBJECTIVE: Polymorphisms in the genes encoding interleukin 4 (IL4), interleukin 13 (IL13), and their corresponding receptors have been associated with multiple immune-mediated diseases. Our aim was to validate these previous observations in patients with systemic sclerosis (SSc) and scrutinize the effect of the polymorphisms on gene expression in various populations of peripheral blood leukocytes. METHODS: We genotyped a cohort of 2488 patients with SSc and 2246 healthy controls from The Netherlands, Spain, United Kingdom, Italy, Germany, and France. Taqman assays were used to genotype single-nucleotide polymorphisms (SNP) in the following genes: (1) IL4 (-590C>T/rs2243250); (2) IL4 receptor alpha (IL4RA) (Q576R/rs1801275); (3) IL13 (R130Q/rs20541 and -1112C>T/rs1800925); and (4) IL13RA1 (43163G>A/rs6646259). The effect of these polymorphisms on expression of the corresponding genes was assessed using quantitative RT-PCR on RNA derived from peripheral blood B cells, T cells, plasmacytoid dendritic cells, monocytes, and myeloid dendritic cells. We investigated whether these polymorphisms influenced development of pulmonary complications over 15 years in patients with SSc. RESULTS: None of the investigated polymorphisms was associated with SSc or any SSc clinical subtype. We did not observe any effect on transcript levels in the cell subtypes or on development of pulmonary complications. CONCLUSION: Our data showed that polymorphisms in IL4, IL13, and their receptors do not play a role in SSc and do not influence the expression of their corresponding transcript in peripheral blood cells.
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