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.
OBJECTIVE
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.
Horiuchi
Takahiko
T
Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. horiuchi@intmed1.med.kyushu-u.ac.jp
Kiyohara
Chikako
C
Tsukamoto
Hiroshi
H
Sawabe
Takuya
T
Furugo
Isao
I
Yoshizawa
Seiji
S
Ueda
Akira
A
Tada
Yoshifumi
Y
Nakamura
Tadashi
T
Kimoto
Yasutaka
Y
Mitoma
Hiroki
H
Harashima
Shinichi
S
Yoshizawa
Shigeru
S
Shimoda
Terufumi
T
Okamura
Seiich
S
Nagasawa
Kohei
K
Harada
Mine
M
D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000208:ethnology / Q000235:genetics*; D011110:Polymorphism, Genetic; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics*
D047889:Receptors, Tumor Necrosis Factor, Type II