Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement

The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.

Association of FAM167A (C8orf13) - BLK Region with Systemic Sclerosis

Ito1,  Ikue, Kawaguchi2,  Yasushi, Kawasaki1,  Aya, Hasegawa3,  Minoru, Ohashi1,  Jun, Kawamoto2,  Manabu, Fujimoto3,  Manabu

University of Tsukuba, Doctoral Program in Life System Medical Sciences, Tsukuba, Japan
Tokyo Women's Medical University, Tokyo, Japan
Kanazawa University, Graduate School of Medical Science, Kanazawa City, Japan
Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan


Association of single nucleotide polymorphisms (SNPs) in FAM167A (C8orf13) - B lymphoid tyrosine kinase (BLK) region with systemic lupus erythematosus (SLE) has been demonstrated in the Caucasian and Asian populations. Recent studies showed that many genes including IRF5, STAT4 and PTPN22 are shared susceptibility genes for multiple autoimmune diseases. This study was performed to examine whether the FAM167A-BLK region is also associated with susceptibility to systemic sclerosis (SSc).


A two-tiered case-control association study was performed on 309 Japanese patients with SSc and 769 healthy controls. Tier-1 examined association of 16 tag SNPs encompassing the FAM167A-BLK region on 124 patients and 412 controls. Tier-2 analyzed additional 185 patients and 357 controls for a SNP rs13277113, selected based on the results of tier-1.


At tier-1, rs13277113 A allele, previously shown to be associated with SLE, demonstrated significant association after correction for multiple testing (permutated P=0.024). Conditional logistic regression analysis revealed that this SNP could account for association of other SNPs. At tier-2, additional 185 patients and 357 controls were genotyped for rs13277113. When tier-1 and tier-2 samples were combined, rs13277113 A allele was significantly associated with SSc and its clinical subsets (Table 1). This association was not observed in the patients who did not possess any of the three major autoantibodies associated with SSc in Japanese: anti-topoisomerase I (anti-topo I), anti-centromere (ACA) and anti-U1 snRNP (anti-RNP) antibodies, suggesting that the genetic effect may be accounted for by autoantibody production.

Table 1. Association of rs13277113 with SSc and its clinical subsets.

 nGenotype, n (%)A allele frequencyAllelic association
all SSc309179 (58)107 (35)23 (7)0.751.45 (1.17–1.79)6.1×10-4
dcSSc15893 (59)54 (34)11 (7)0.761.50 (1.14–1.98)0.0041
lcSSc15186 (57)53 (35)12 (8)0.751.39 (1.05–1.84)0.021
anti-topo I, ACA or anti-RNP Ab positive208127 (61)68 (33)13 (6)0.771.63 (1.27–2.10)1.1×10-4
anti-topo I, ACA and anti-RNP Ab negative10152 (51)39 (39)10 (10)0.711.15 (0.84–1.59)0.38
healthy controls769354 (46)334 (43)81 (11)0.68referent


The rs13277113 A allele is associated not only with SLE but also with SSc. The association was preferentially observed in autoantibody-positive patients. These findings indicate that the FAM167A-BLK region is a common genetic risk factor for SLE and SSc.

To cite this abstract, please use the following information:
Ito, Ikue, Kawaguchi, Yasushi, Kawasaki, Aya, Hasegawa, Minoru, Ohashi, Jun, Kawamoto, Manabu, et al; Association of FAM167A (C8orf13) - BLK Region with Systemic Sclerosis [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1800
DOI: 10.1002/art.26874

Abstract Supplement

Meeting Menu