TY - JOUR
T1 - Polymorphisms in the interleukin 4, interleukin 13, and corresponding receptor genes are not associated with systemic sclerosis and do not influence gene expression
AU - Broen, Jasper C A
AU - Dieude, Phillipe
AU - Vonk, Madelon C.
AU - Beretta, Lorenzo
AU - Carmona, Francisco D.
AU - Herrick, Ariane
AU - Worthington, Jane
AU - Hunzelmann, Nicholas
AU - Riemekasten, Gabriela
AU - Kiener, Hans
AU - Scorza, Rafaella
AU - Simeon, Carmen P.
AU - Fonollosa, Vicent
AU - Carreira, Patricia
AU - Ortego-Centeno, Norberto
AU - Gonzalez-Gay, Miguel A.
AU - Airo', Paolo
AU - Coenen, Marieke J.
AU - Tsang, Kelly
AU - Aliprantis, Antonios O.
AU - Martin, Javier
AU - Allanore, Yannick
AU - Radstake, Timothy R D J
PY - 2012/1
Y1 - 2012/1
N2 - 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. The Journal of Rheumatology Copyright © 2012. All rights reserved.
AB - 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. The Journal of Rheumatology Copyright © 2012. All rights reserved.
KW - Interleukin 13
KW - Interleukin 4
KW - Single-nucleotide polymorphism
KW - Systemic sclerosis
U2 - 10.3899/jrheum.110235
DO - 10.3899/jrheum.110235
M3 - Article
C2 - 22045834
SN - 1499-2752
VL - 39
SP - 112
EP - 118
JO - Journal of Rheumatology
JF - Journal of Rheumatology
IS - 1
ER -
