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A functional M196R polymorphism of tumour necrosis factor receptor type 2 is associated with systemic lupus erythematosus: a case–control study and a meta-analysis
  1. Takahiko Horiuchi1,
  2. Chikako Kiyohara2,
  3. Hiroshi Tsukamoto1,
  4. Takuya Sawabe3,
  5. Isao Furugo4,
  6. Seiji Yoshizawa5,
  7. Akira Ueda6,
  8. Yoshifumi Tada7,
  9. Tadashi Nakamura8,
  10. Yasutaka Kimoto1,
  11. Hiroki Mitoma1,
  12. Shinichi Harashima1,
  13. Shigeru Yoshizawa9,
  14. Terufumi Shimoda9,
  15. Seiich Okamura10,
  16. Kohei Nagasawa7,
  17. Mine Harada1
  1. 1Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
  2. 2Department of Preventive Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
  3. 3Hiroshima Red Cross Hospital and Atomic-bomb Survivor’s Hospital, Hiroshima, Japan
  4. 4Kitakyushu Municipal Medical Center, Kitakyushu, Japan
  5. 5Munakata Medical Association Hospital, Munakata, Japan
  6. 6Miyazaki Prefectural Miyazaki Hospital, Miyazaki, Japan
  7. 7Department of Internal Medicine, Saga University, Saga, Japan
  8. 8Kumamoto Center for Arthritis and Rheumatology, Kumamoto, Japan
  9. 9Department of Clinical Research, Fukuoka National Hospital, Fukuoka, Japan
  10. 10Clinical Research Center, National Kyushu Medical Center Hospital, Fukuoka, Japan
  1. Correspondence to:
    Assistant Professor T Horiuchi
    Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan; horiuchi{at}intmed1.med.kyushu-u.ac.jp

Abstract

Objectives: To perform a case–control study of a functional M196R polymorphism of tumour necrosis factor receptor type 2 (TNF-RII) in a Japanese population and a meta-analysis of all published reports on the polymorphism to investigate the association of the M196R polymorphism of TNF-RII with systemic lupus erythematosus (SLE).

Methods: The functional M196R polymorphism of TNF-RII was genotyped by using polymerase chain reaction combined with the subsequent single-strand conformation polymorphism (PCR—SSCP) analysis for screening, followed by nucleotide sequencing for confirmation. A total of 331 patients and 359 controls were subjected to a case–control study. A meta-analysis of the available case–control studies including all published data as well as our own data was performed to investigate the association of the functional M196R polymorphism of TNF-RII with SLE.

Results: Our case–control study did not show any significant association of a functional M196R polymorphism of TNF-RII with SLE, although there was a trend towards association. A meta-analysis of seven case–control studies in eight different ethnic populations including our own showed that 196M/R and 196R/R genotypes combined was significantly associated with an increased risk of SLE (odds ratio (OR) 1.29, 95% confidence interval (CI) 1.04 to 1.60; p = 0.02). Stratification by ethnicity showed a more significant association in Asians, including Japanese, Korean and Vietnamese (OR 1.40, 95% CI 1.10 to 1.78; p = 0.006). The effect of the 196R allele on SLE was not clear in Caucasians.

Conclusions: The 196R allele of the functional M196R polymorphism of TNF-RII is a risk factor for SLE, especially in the Asian population.

  • PCR, polymerase chain reaction
  • SSCP, single-strand conformation polymorphism
  • SLE, systemic lupus erythematosus
  • TNF-RII, tumour necrosis factor receptor type 2

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Footnotes

  • Published Online First 6 October 2006

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