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A replication study confirms the association of TNFSF4 (OX40L) polymorphisms with systemic sclerosis in a large European cohort.

Bossini-Castillo, Lara; Broen, Jasper C A; Simeon, Carmen P; Beretta, Lorenzo; Vonk, Madelon C; Ortego-Centeno, Norberto; Espinosa, Gerard; Carreira, Patricia; Camps, María Teresa; Navarrete, Nuria; González-Escribano, María F; Vicente-Rabaneda, Esther; Rodríguez, Luis; Tolosa, Carlos; Román-Ivorra, José A; Gómez-Gracia, Inmaculada; García-Hernández, Francisco J; Castellví, Iván; Gallego, María; Fernández-Nebro, Antonio; García-Portales, Rosa; Egurbide, María Victoria; Fonollosa, Vicente; de la Peña, Paloma García; Pros, Ana; González-Gay, Miguel A; Hesselstrand, Roger; Riemekasten, Gabriela; Witte, Torsten; Coenen, Marieke J H; Koeleman, Bobby P; Houssiau, Frederic; Smith, Vanessa; de Keyser, Filip; Westhovens, Rene; De Langhe, Ellen; Voskuyl, Alexandre E; Schuerwegh, Annemie J; Chee, Meng May; Madhok, Rajan; Shiels, Paul; Fonseca, Carmen; Denton, Christopher; Claes, Kathleen; Padykov, Leonid; Nordin, Annika; Palm, Oyvind; Lie, Benedicte A; Airó, Paolo; Scorza, Raffaella; van Laar, Jacob M; Hunzelmann, Nicolas; Kreuter, Alexander; Herrick, Ariane; Worthington, Jane; Radstake, Timothy R D J; Martín, Javier; Rueda, Blanca

Annals of the rheumatic diseases. 2011;70(4):638-641.

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Abstract

OBJECTIVES: /st> The aim of this study was to confirm the influence of TNFSF4 polymorphisms on systemic sclerosis (SSc) susceptibility and phenotypic features. METHODS: /st> A total of 8 European populations of Caucasian ancestry were included, comprising 3014 patients with SSc and 3125 healthy controls. Four genetic variants of TNFSF4 gene promoter (rs1234314, rs844644, rs844648 and rs12039904) were selected as genetic markers. RESULTS: /st> A pooled analysis revealed the association of rs1234314 and rs12039904 polymorphisms with SSc (OR 1.15, 95% CI 1.02 to 1.31; OR 1.18, 95% CI 1.08 to 1.29, respectively). Significant association of the four tested variants with patients with limited cutaneous SSc (lcSSc) was revealed (rs1234314 OR 1.22, 95% CI 1.07 to 1.38; rs844644 OR 0.91, 95% CI 0.83 to 0.99; rs844648 OR 1.10, 95% CI 1.01 to 1.20 and rs12039904 OR 1.20, 95% CI 1.09 to 1.33). Association of rs1234314, rs844648 and rs12039904 minor alleles with patients positive for anti-centromere antibodies (ACA) remained significant (OR 1.23, 95% CI 1.10 to 1.37; OR 1.12, 95% CI 1.01 to 1.25; OR 1.22, 95% CI 1.07 to 1.38, respectively). Haplotype analysis confirmed a protective haplotype associated with SSc, lcSSc and ACA positive subgroups (OR 0.88, 95% CI 0.82 to 0.96; OR 0.88, 95% CI 0.80 to 0.96; OR 0.86, 95% CI 0.77 to 0.97, respectively) and revealed a new risk haplotype associated with the same groups of patients (OR 1.14, 95% CI 1.03 to 1.26; OR 1.20, 95% CI 1.08 to 1.35; OR 1.23, 95% CI 1.07 to 1.42, respectively). CONCLUSIONS: /st> The data confirm the influence of TNFSF4 polymorphisms in SSc genetic susceptibility, especially in subsets of patients positive for lcSSc and ACA.

Bibliographic metadata

Type of resource:

text

Content type:

Journal article

Publication type:

Original research

Publication form:

Academic journal article

Author(s):

Published date:

2011-27

Article title:

A replication study confirms the association of TNFSF4 (OX40L) polymorphisms with systemic sclerosis in a large European cohort.

Journal title:

Annals of the rheumatic diseases

Abbreviated journal title:

Ann Rheum Dis

ISSN:

1468-2060

Volume:

Issue:

Start page:

638

End page:

641

Digital Object Identifier:

10.1136/ard.2010.141838

Pubmed Identifier:

21187296

Pii Identifier:

ard.2010.141838

Access state:

Active

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University researcher(s):

Academic department(s):

Record metadata

Manchester eScholar ID:

uk-ac-man-scw:103644

Created by:

Ingram, Mary

Created:

6th January, 2011, 14:37:16

Last modified by:

Ingram, Mary

Last modified:

18th December, 2013, 19:24:35