Association of the TNFAIP3 rs5029939 variant with systemic sclerosis in the European Caucasian population

被引：115

作者：

Dieude, P. ^{[2
]}

Guedj, M. ^{[3
]}

Wipff, J. ^{[1
,4
]}

Ruiz, B. ^{[4
]}

Riemekasten, G. ^{[5
]}

Matucci-Cerinic, M. ^{[6
]}

Melchers, I. ^{[7
]}

Hachulla, E. ^{[8
]}

Airo, P. ^{[9
]}

Diot, E. ^{[10
]}

Hunzelmann, N. ^{[11
]}

Cabane, J. ^{[12
]}

Mouthon, L.

Cracowski, J. L. ^{[13
]}

Riccieri, V. ^{[14
]}

Distler, J. ^{[15
,16
]}

Meyer, O.

Kahan, A. ^{[1
]}

Boileau, C. ^{[4
,17
]}

Allanore, Y. ^{[1
,4
]}

机构：

[1] Univ Paris 05, Serv Rhumatol A, Hop Cochin, F-75014 Paris, France

[2] Univ Paris 07, Serv Rhumatol, Hop Bichat Claude Bernard, APHP, Paris, France

[3] Univ Evry Val Essonne, Lab Stat & Genome, UMR CNRS 8071, INRA 1152, Paris, France

[4] Univ Paris 05, INSERM U781, Hop Necker, F-75014 Paris, France

[5] Charite, Dept Rheumatol & Clin Immunol, Berlin, Germany

[6] Dept Biomed, Rheumatol Sect, Florence, Italy

[7] Univ Med Ctr, Clin Res Unit Rheumatol, Freiburg, Germany

[8] Univ Lille 2, Lille, France

[9] Spedali Civil Brescia, I-25125 Brescia, Italy

[10] CHU Bretonneau, INSERM U618, IFR 135, F-37044 Tours, France

[11] Univ Cologne, Dept Dermatol, D-5000 Cologne, Germany

[12] Univ Paris 06, Serv Med Interne, Hop St Antoine, APHP, Paris, France

[13] CHU Grenoble, INSERM CIC3, Grenoble, France

[14] Univ Roma La Sapienza, Dept Med Clin & Therapy, Rome, Italy

[15] Univ Erlangen Nurnberg, Dept Internal Med 3, D-8520 Erlangen, Germany

[16] Univ Erlangen Nurnberg, Inst Clin Immunol, D-8520 Erlangen, Germany

[17] Univ Versailles St Quentin Yvelines, Lab Biochim Hormonale & Genet, Hop Ambroise Pare, AP HP, Boulogne, France

来源：

ANNALS OF THE RHEUMATIC DISEASES | 2010年 / 69卷 / 11期

关键词：

GENETIC RISK-FACTOR; FUNCTIONAL POLYMORPHISM; IRF5; SUSCEPTIBILITY; STAT4; INFLAMMATION; SCLERODERMA; FREQUENCY; SUBSETS; REGION;

D O I：

10.1136/ard.2009.127928

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：1958 / 1964

页数：7

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