Tumor necrosis factor microsatellite alleles in patients with rheumatoid arthritis in Taiwan.
OBJECTIVE
To investigate the association of tumor necrosis factor (TNF) microsatellite alleles with the pathogenesis of rheumatoid arthritis (RA) in Taiwan.


METHODS
The TNF a, b, c, d, and e microsatellites were determined in 112 patients with RA and 99 healthy controls by using polymerase chain reaction (PCR) and electrophoresis with sequencing gel. All of these patients and controls had known HLA-DR genotypes and TNF-308 polymorphisms.


RESULTS
The phenotypic frequency of TNFa9 was significantly higher in DR4(-) RA patients than in DR4(-) controls. However, the phenotypic frequency of TNFb6 was significantly higher in RA patients than in controls in the presence of HLA-DR4. The phenotypic frequency of TNFa3-e1 was significantly lower in DR4(+) RA patients than in DR4(+) controls, while a negative linkage disequilibrium was noted between TNFa3-e1 and HLA-DR4. TNF microsatellite alleles were not related to the prevalences of bone erosion, rheumatoid nodule, sicca syndrome, pulmonary fibrosis, and seropositivity of rheumatoid factor (RF) in patients with RA.


CONCLUSIONS
The associations of TNF microsatellites with the susceptibility to RA in Taiwan are not completely independent of the HLA-DR associations. The association of TNFb6 with the susceptibility to RA depends on the presence of HLA-DR4, and the correlation of TNFa9 to RA depends on the absence of HLA-DR4. The negative association of TNFa3-e1 with RA may be secondary to the negative linkage disequilibrium between TNFa3-e1 and HLA-DR4. Moreover, TNFb6 and HLA-DR4 have a synergistic effect on the susceptibility to RA. TNFa3-e1 and TNF-308A have a synergistic effect on preventing from RA. The TNF microsatellite alleles are not related to the clinical manifestations and severity of RA patients in Taiwan.
Yen
Jeng-Hsien
JH
Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Kaohsiung Medical University Hospital, No. 100 Shih-Chuan, 1st Road, Kaohsiung807, Taiwan. jehsye@cc.kmu.edu.tw
Chen
Chung-Jen
CJ
Tsai
Wen-Chun
WC
Lin
Chia-Hui
CH
Ou
Tsan-Teng
TT
Lin
Shih-Chang
SC
Dai
Zen-Kong
ZK
Liu
Hong-Wen
HW
D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D018895:Microsatellite Repeats; D010641:Phenotype; D013624:Taiwan; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha