David Carmona, F., Carmen Cenit, M., Diaz-Gallo, Lina-Marcela, Broen, Jasper C. A., Simeon, Carmen P., Carreira, Patricia E., Callejas-Rubio, Jose-Luis, Fonollosa, Vicente, Lopez-Longo, Francisco J., Gonzalez-Gay, Miguel A. ORCID: 0000-0002-7924-7406, Hunzelmann, Nicolas, Riemekasten, Gabriela, Witte, Torsten, Kreuter, Alexander, Distler, Joerg H. W., Madhok, Rajan, Shiels, Paul ORCID: 0000-0002-7577-9843, van Laar, Jacob M., Schuerwegh, Annemie J., Vonk, Madelon C., Voskuyl, Alexandre E., Fonseca, Carmen, Denton, Christopher P., Herrick, Ariane ORCID: 0000-0003-4941-7926, Worthington, Jane ORCID: 0000-0003-0544-042X, Arnett, Frank C., Tan, Filemon K., Assassi, Shervin, Radstake, Timothy R. D. J., Mayes, Maureen D. and Martin, Javier ORCID: 0000-0002-2202-0622 (2013). New insight on the Xq28 association with systemic sclerosis. Ann. Rheum. Dis., 72 (12). S. 2032 - 2039. LONDON: BMJ PUBLISHING GROUP. ISSN 1468-2060

Full text not available from this repository.

Abstract

Objective To evaluate whether the systemic sclerosis (SSc)-associated IRAK1 non-synonymous single-nucleotide polymorphism rs1059702 is responsible for the Xq28 association with SSc or whether there are other independent signals in the nearby methyl-CpG-binding protein 2 gene (MECP2). Methods We analysed a total of 3065 women with SSc and 2630 unaffected controls from five independent Caucasian cohorts. Four tag single-nucleotide polymorphisms of MECP2 (rs3027935, rs17435, rs5987201 and rs5945175) and the IRAK1 variant rs1059702 were genotyped using TaqMan predesigned assays. A meta-analysis including all cohorts was performed to test the overall effect of these Xq28 polymorphisms on SSc. ResultsIRAK1 rs1059702 and MECP2 rs17435 were associated specifically with diffuse cutaneous SSc (P-FDR=4.12x10(-3), OR=1.27, 95% CI 1.09 to 1.47, and P-FDR=5.26x10(-4), OR=1.30, 95% CI 1.14 to 1.48, respectively), but conditional logistic regression analysis showed that the association of IRAK1 rs1059702 with this subtype was explained by that of MECP2 rs17435. On the other hand, IRAK1 rs1059702 was consistently associated with presence of pulmonary fibrosis (PF), because statistical significance was observed when comparing SSc patients PF+ versus controls (P-FDR=0.039, OR=1.30, 95% CI 1.07 to 1.58) and SSc patients PF+ versus SSc patients PF- (p=0.025, OR=1.26, 95% CI 1.03 to 1.55). Conclusions Our data clearly suggest the existence of two independent signals within the Xq28 region, one located in IRAK1 related to PF and another in MECP2 related to diffuse cutaneous SSc, indicating that both genes may have an impact on the clinical outcome of the disease.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
David Carmona, F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Carmen Cenit, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Diaz-Gallo, Lina-MarcelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Broen, Jasper C. A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Simeon, Carmen P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Carreira, Patricia E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Callejas-Rubio, Jose-LuisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fonollosa, VicenteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lopez-Longo, Francisco J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gonzalez-Gay, Miguel A.UNSPECIFIEDorcid.org/0000-0002-7924-7406UNSPECIFIED
Hunzelmann, NicolasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Riemekasten, GabrielaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Witte, TorstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kreuter, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Distler, Joerg H. W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Madhok, RajanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shiels, PaulUNSPECIFIEDorcid.org/0000-0002-7577-9843UNSPECIFIED
van Laar, Jacob M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schuerwegh, Annemie J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vonk, Madelon C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Voskuyl, Alexandre E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fonseca, CarmenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Denton, Christopher P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Herrick, ArianeUNSPECIFIEDorcid.org/0000-0003-4941-7926UNSPECIFIED
Worthington, JaneUNSPECIFIEDorcid.org/0000-0003-0544-042XUNSPECIFIED
Arnett, Frank C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tan, Filemon K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Assassi, ShervinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Radstake, Timothy R. D. J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mayes, Maureen D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Martin, JavierUNSPECIFIEDorcid.org/0000-0002-2202-0622UNSPECIFIED
URN: urn:nbn:de:hbz:38-471229
DOI: 10.1136/annrheumdis-2012-202742
Journal or Publication Title: Ann. Rheum. Dis.
Volume: 72
Number: 12
Page Range: S. 2032 - 2039
Date: 2013
Publisher: BMJ PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 1468-2060
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
LUPUS-ERYTHEMATOSUS; X-CHROMOSOME; GENE-EXPRESSION; MECP2; DISEASE; IRAK1; SUSCEPTIBILITY; PATHOGENESIS; VARIANTS; RISKMultiple languages
RheumatologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/47122

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item