Universität zu Köln

Dieude, P., Guedj, M., Wipff, J., Ruiz, B., Riemekasten, G., Matucci-Cerinic, M., Melchers, I., Hachulla, E., Airo, P., Diot, E., Hunzelmann, N., Cabane, J., Mouthon, L., Cracowski, J. L., Riccieri, V., Distler, J., Meyer, O., Kahan, A., Boileau, C. and Allanore, Y. (2010). Association of the TNFAIP3 rs5029939 variant with systemic sclerosis in the European Caucasian population. Ann. Rheum. Dis., 69 (11). S. 1958 - 1965. LONDON: BMJ PUBLISHING GROUP. ISSN 1468-2060

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Abstract

Background TNFAIP3 encodes the ubiquitin-modifying enzyme, a key regulator of inflammatory signalling pathways. Convincing associations between TNFAIP3 variants and autoimmune diseases have been reported. Objective To investigate the association of TNFAIP3 polymorphisms with systemic sclerosis (SSc). Methods Three single nucleotide polymorphisms (SNPs) in a set of 1018 patients with SSc and 1012 controls of French Caucasian origin were genotyped. Two intergenic SNPs, rs10499194 and rs6920220, and one located in TNFAIP3 intron 2, rs5029939, were selected. The TNFAIP3 rs5029939 found to be associated with SSc in this first set was then genotyped in a second set of 465 patients with SSc and 182 controls from Germany and 184 patients with SSc and 124 controls from Italy. Pooled odd ratios were calculated by Mantel-Haenszel meta-analysis. Results The rs5029939 G allele was found to be significantly associated with SSc susceptibility (pooled OR=2.08 (95% CI 1.59 to 2.72); p=1.16x10(-7)), whereas the rs10499194 and rs6920220 variants displayed no association. Only one of the predicted haplotypes investigated in the French sample was significantly associated with SSc (p=8.91x10(-8)), and this haplotype was discriminating only in the presence of the rs5029939 risk allele, suggesting that this SNP tags the association signal. The strongest associations of rs5029939 with subphenotypes, having large magnitudes for complex genetic disorders, were observed for diffuse cutaneous SSc (pooled OR=2.71 (1.94 to 3.79), p=5.2x10(-9)), fibrosing alveolitis (pooled OR=2.26 (1.61 to 3.17), p=2.5x10(-6)) and pulmonary arterial hypertension (pooled OR=3.11 (1.86 to 5.17), p=1.3x10(-5)). Conclusion These results suggest that TNFAIP3 is a genetic susceptibility factor for SSc.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Dieude, P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Guedj, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wipff, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ruiz, B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Riemekasten, G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Matucci-Cerinic, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Melchers, I. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hachulla, E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Airo, P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Diot, E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hunzelmann, N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cabane, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mouthon, L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Cracowski, J. L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Riccieri, V. UNSPECIFIED UNSPECIFIED UNSPECIFIED Distler, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Meyer, O. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kahan, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Boileau, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Allanore, Y. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-492891
DOI:	10.1136/ard.2009.127928
Journal or Publication Title:	Ann. Rheum. Dis.
Volume:	69
Number:	11
Page Range:	S. 1958 - 1965
Date:	2010
Publisher:	BMJ PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	1468-2060
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GENETIC RISK-FACTOR; FUNCTIONAL POLYMORPHISM; IRF5; SUSCEPTIBILITY; STAT4; INFLAMMATION; SCLERODERMA; FREQUENCY; SUBSETS; REGION Multiple languages Rheumatology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/49289