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 In contrast, previously unpublished results from the SLEGEN study shows significant association of the same allele (OR 1.19, p=0.0038) with an overall effect of 1.22 (p=1.02x10-6) in a total of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.