The TRAF1-C5 region on chromosome 9q33 is associated with multiple autoimmune diseases.
OBJECTIVE
The TRAF1-C5 locus has recently been identified as a genetic risk factor for rheumatoid arthritis (RA). Since genetic risk factors tend to overlap with several autoimmune diseases, a study was undertaken to investigate whether this region is associated with type 1 diabetes (TID), celiac disease (CD), systemic sclerosis (SSc) and systemic lupus erythematosus (SLE).


METHODS
The most consistently associated SNP, rs10818488, was genotyped in a total of 735 patients with T1D, 1049 with CD, 367 with SSc, 746 with SLE and 3494 ethnically- and geographically-matched healthy individuals. The replication sample set consisted of 99 patients with T1D, 272 with SLE and 482 healthy individuals from Crete.


RESULTS
A significant association was detected between the rs10818488 A allele and T1D (OR 1.14, p=0.027) and SLE (OR 1.16, p=0.016), which was replicated in 99 patients with T1D, 272 with SLE and 482 controls from Crete (OR 1.64, p=0.002; OR 1.43, p=0.002, respectively). Joint analysis of all patients with T1D (N=961) and all patients with SLE (N=1018) compared with 3976 healthy individuals yielded an allelic common OR of 1.19 (p=0.002) and 1.22 (p=2.6 x 10(-4)), respectively. However, combining our dataset with the T1D sample set from the WTCCC resulted in a non-significant association (OR 1.06, p=0.087). In contrast, previously unpublished results from the SLEGEN study showed a significant association of the same allele (OR 1.19, p=0.0038) with an overall effect of 1.22 (p=1.02 x 10(-6)) in a total of 1577 patients with SLE and 4215 healthy individuals.


CONCLUSIONS
A significant association was found for the TRAF1-C5 locus in SLE, implying that this region lies in a pathway relevant to multiple autoimmune diseases.
Kurreeman
Fina A S
FA
Department of Rheumatology, Leiden University Medical Center, Albinusdreef 2, Leiden, The Netherlands.
Goulielmos
George N
GN
Alizadeh
Behrooz Z
BZ
Rueda
Blanca
B
Houwing-Duistermaat
Jeanine
J
Sanchez
Elena
E
Bevova
Marianna
M
Radstake
Timothy R
TR
Vonk
Madelon C
MC
Galanakis
Emmanouil
E
Ortego
Norberto
N
Verduyn
Willem
W
Zervou
Maria I
MI
Roep
Bart O
BO
Dema
Barbara
B
Espino
Laura
L
Urcelay
Elena
E
Boumpas
Dimitrios T
DT
van den Berg
Leonard H
LH
Wijmenga
Cisca
C
Koeleman
Bobby P C
BP
Huizinga
Tom W J
TW
Toes
Rene E M
RE
Martin
Javier
J
D001327:Autoimmune Diseases / Q000235:genetics*; D002446:Celiac Disease / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012595:Scleroderma, Systemic / Q000235:genetics; D047990:TNF Receptor-Associated Factor 1 / Q000235:genetics*
D047990:TNF Receptor-Associated Factor 1