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Replication of association between FAM167A(C8orf13)-BLK region and rheumatoid arthritis in a Japanese population
  1. Ikue Ito1,
  2. Aya Kawasaki1,
  3. Satoshi Ito2,
  4. Yuya Kondo2,
  5. Makoto Sugihara2,
  6. Masanobu Horikoshi2,
  7. Taichi Hayashi2,
  8. Daisuke Goto2,
  9. Isao Matsumoto2,
  10. Akito Tsutsumi3,
  11. Yoshinari Takasaki4,
  12. Hiroshi Hashimoto5,
  13. Kunio Matsuta6,
  14. Takayuki Sumida2,
  15. Naoyuki Tsuchiya1
  1. 1Molecular and Genetic Epidemiology Laboratory, Doctoral Program in Life System Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan
  2. 2Division of Clinical Immunology, Doctoral Program in Clinical Sciences, Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba, Japan
  3. 3Takikawa Municipal Hospital, Takikawa, Japan
  4. 4Division of Rheumatology, Department of Medicine, Juntendo University, Tokyo, Japan
  5. 5Juntendo University School of Medicine, Tokyo, Japan
  6. 6Matsuta Clinic, Tokyo, Japan
  1. Correspondence to Dr Naoyuki Tsuchiya, Doctoral Program in Life System Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan; tsuchiya-tky{at}

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Polymorphisms in the genomic region encoding B lymphoid tyrosine kinase (BLK) and family with sequence similarity 167, member A (FAM167A, also referred to as C8orf13) at 8p23.1 have been associated with systemic lupus erythematosus (SLE) in Caucasian1 2 and Asian3 4 populations. A recent genome-wide study in a north American population showed new associations with rheumatoid arthritis (RA), among which was a single nucleotide polymorphism (SNP) rs2736340 in the intergenic region of BLK and FAM167A.5 In the HapMap Japanese samples (, this SNP is in absolute linkage disequilibrium (r2=1) with rs13277113, previously associated with SLE.1,,4 We have shown that the population frequency of the risk genotype rs13277113A/A and the OR for SLE were substantially higher in the Japanese population than in the Caucasian population.3

To date, the association of FAM167A-BLK region with RA has not been reported in non-Caucasian populations. In this study we examined whether the association between BLK and RA was replicated in Japanese subjects.

A case-control association study was performed for 603 patients and 492 healthy controls. Because the association of FAM167A-BLK region with SLE is already established,1,,4 patients with RA complicated with SLE were excluded. All patients fulfilled the American College of Rheumatology classification criteria for RA.6 The patients and the healthy controls were recruited at Matsuta Clinic, University of Tsukuba, the University of Tokyo and Juntendo University. This study was reviewed and approved by the research ethics committees of University of Tsukuba and other participating institutes. Written informed consent was obtained from all participants, except for some participants before 2001, before the enforcement of the Ethics Guidelines for Human Genome/Gene Analysis Research by the Japanese government. From such participants, oral informed consent had been obtained. In accordance with the guidelines, the latter samples were anonymised in an unlinkable fashion and were included in this study after review and approval by the ethics committee of University of Tsukuba. The genotype of rs13277113 was determined using the TaqMan SNP genotyping assay (Applied Biosystems, Foster City, California, USA).3 Power calculation based on the risk allele frequency in the Japanese population (0.665) showed that this sample size provides 80% power to detect susceptibility genes with an allelic OR of 1.298. Deviation from Hardy-Weinberg equilibrium was observed neither in the patients nor in the controls.

A significant association with RA was replicated in the Japanese population (table 1). Although the OR was comparable to that in the Caucasian population (1.19 for rs27363405), the risk allele frequency was considerably higher in the Japanese subjects than in the Caucasians (0.273 in cases vs 0.240 in controls for rs27363405). The population attributable risk percentage was estimated to be 22.8% in the Japanese population and 9.3% in the Caucasian population under the dominant model. No significant difference in rs13277113 was observed between HLA-DRB1 shared epitope positive and negative RA (data not shown).

Table 1

Association of BLK rs13277113 with rheumatoid arthritis (RA) in a Japanese population

Our observations indicate that the FAM167A-BLK region may be a shared genetic factor for a number of autoimmune diseases in multiple populations, but the genetic contribution may be greater in Asian populations because of the differences in the genetic background.



  • Funding This work was supported by Grant-in-Aid for Scientific Research (B) from Japan Society for the Promotion of Science (JSPS), Health and Labour Science Research Grants from the Ministry of Health, Labour and Welfare of Japan, Japan Rheumatism Foundation, The Naito Foundation and Mitsubishi Pharma Research Foundation.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the University of Tsukuba, Juntendo University and the University of Tokyo.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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