RESEARCH - The TRAF1-C5 region on chromosome 9q33 is associated with multiple autoimmune diseases

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Ann Rheum Dis. Published Online First: 10 May 2009. doi:10.1136/ard.2008.106567

BMJ Publishing Group Ltd & European League Against Rheumatism.

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Extended Report

The TRAF1-C5 region on chromosome 9q33 is associated with multiple

autoimmune diseases

Fina AS Kurreeman 1, N Goulielmos 2, Behrooz Z Alizadeh 3,

Blanca Rueda 4, Jeanine Houwing-Duistermaat 1, Elena Sánchez 4,

nna Bevova 3, R Radstake 5, Madelon C Vonk 5, Emmanouil

Galanakis 2, Norberto Ortego 6, Willem Verduyn 1, I Zervou 2,

SLEGEN Consortium 7, Bart O Roep 1, Barbara Dema 6, Espino 6,

Elena Urcelay 8, Dimitri T Boumpas 2, Leonard H van den Berg 3, Ciska

Wijmenga 3, Bobby PC Koeleman 3, Tom W J Huizinga 1, Rene E M Toes 1*

and 4

1 LUMC, Netherlands

2 University of Crete, Greece

3 University Medical Center Utrecht, Netherlands

4 Consejo Superior de Investigaciones Científicas, Spain

5 Radboud University Nijmegen Medical Center, Netherlands

6 Hospital Clínico San Cecilio, Spain

7 -, United States

8 Hospital Clínico San , Madrid, Spain

Abstract

Objectives: The TRAF1-C5 locus has recently been identified as a

genetic risk factor for rheumatoid arthritis. Since genetic risk

factors tend to overlap with several autoimmune diseases, we aimed to

investigate whether this region is associated with Type I Diabetes

(TID), Celiac Disease (CD), Systemic Sclerosis (SSc) and Systemic

Lupus Erythematosus (SLE).

Methods: We genotyped the most consistently associated SNP,

rs10818488, in a total of 735 T1D, 1049 CD, 367 SSc, 746 SLE and 3494

ethnically and geographically matched healthy individuals. The

replication sample set consisted of 99 T1D, 272 SLE patients and 482

healthy individuals from Crete.

Results: We detected significant association of the rs10818488 A

allele with T1D (OR 1.14, p=0.027) and SLE (OR 1.16, p=0.016) which

was replicated in 99 T1D, 272 SLE patients and 482 controls from Crete

(OR 1.64, p=0.002; OR 1.43, p=0.002 respectively). Joint analysis of

all T1D (N=961) and all SLE (N=1018) patients compared to 3976 healthy

individuals yielded an allelic common OR of 1.19 (p=0.002) and 1.22

(P=2.6x10-4) respectively. However, combining our dataset with the T1D

sample set from the WTCCC results in a non-significant association (OR

1.06, p=0.087). In contrast, previously unpublished results from the

SLEGEN study shows significant association of the same allele (OR

1.19, p=0.0038) with an overall effect of 1.22 (p=1.02x10-6) in a

total of 1577 SLE patients and 4215 healthy individuals.

Conclusion: We report significant association of the TRAF1-C5 locus in

SLE implying that this region lies in a pathway relevant to multiple

autoimmune diseases.

http://ard.bmj.com/cgi/content/abstract/ard.2008.106567v3?papetoc

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