EXTENDED REPORT

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

Takahiko Horiuchi¹, Chikako Kiyohara², Hiroshi Tsukamoto¹, Takuya Sawabe³, Isao Furugo⁴, Seiji Yoshizawa⁵, Akira Ueda⁶, Yoshifumi Tada⁷, Tadashi Nakamura⁸, Yasutaka Kimoto¹, Hiroki Mitoma¹, Shinichi Harashima¹, Shigeru Yoshizawa⁹, Terufumi Shimoda⁹, Seiich Okamura¹⁰, Kohei Nagasawa⁷, Mine Harada¹

¹ Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
² Department of Preventive Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
³ Hiroshima Red Cross Hospital and Atomic-bomb Survivor’s Hospital, Hiroshima, Japan
⁴ Kitakyushu Municipal Medical Center, Kitakyushu, Japan
⁵ Munakata Medical Association Hospital, Munakata, Japan
⁶ Miyazaki Prefectural Miyazaki Hospital, Miyazaki, Japan
⁷ Department of Internal Medicine, Saga University, Saga, Japan
⁸ Kumamoto Center for Arthritis and Rheumatology, Kumamoto, Japan
⁹ Department of Clinical Research, Fukuoka National Hospital, Fukuoka, Japan
¹⁰ Clinical Research Center, National Kyushu Medical Center Hospital, Fukuoka, Japan

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

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.

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

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• KIYOHARA, C., WASHIO, M., HORIUCHI, T., TADA, Y., ASAMI, T., IDE, S., ATSUMI, T., KOBASHI, G., TAKAHASHI, H. (2009). Cigarette Smoking, STAT4 and TNFRSF1B Polymorphisms, and Systemic Lupus Erythematosus in a Japanese Population. The Journal of Rheumatology 36: 2195-2203 [Abstract] [Full Text]  
• Horiuchi, T., Washio, M., Kiyohara, C., Tsukamoto, H., Tada, Y., Asami, T., Ide, S., Kobashi, G., Takahashi, H., the Kyushu Sapporo SLE Study Group, (2009). Combination of TNF-RII, CYP1A1 and GSTM1 polymorphisms and the risk of Japanese SLE: findings from the KYSS study. Rheumatology (Oxford) 48: 1045-1049 [Abstract] [Full Text]  
• Tamimoto, Y., Horiuchi, T., Tsukamoto, H., Otsuka, J., Mitoma, H., Kimoto, Y., Nakashima, H., Muta, K., Abe, Y., Kiyohara, C., Ueda, A., Nagasawa, K., Yoshizawa, S., Shimoda, T., Harada, M. (2008). A dose-escalation study of rituximab for treatment of systemic lupus erythematosus and Evans' syndrome: immunological analysis of B cells, T cells and cytokines. Rheumatology (Oxford) 47: 821-827 [Abstract] [Full Text]  
• Miceli-Richard, C., Dieude, P., Hachulla, E., Puechal, X., Cornelis, F., Mariette, X. (2007). Tumour necrosis factor receptor 2 (TNFRSF1B) association study in Sjogren's syndrome. Ann Rheum Dis 66: 1684-1685 [Full Text]