Tristetraprolin (TTP) gene polymorphisms in patients with rheumatoid arthritis and healthy individuals.
Tristetraprolin (TTP) is an intracellular protein that modulates the production of cytokines, including TNFalpha, by binding to and destabilizing the mRNAs of these cytokines. Therefore, differences in TTP gene expression may affect the severity of inflammatory diseases, such as rheumatoid arthritis (RA). We searched for polymorphisms in the human TTP gene and for this purpose, we sequenced the entire TTP gene in 20 Japanese individuals (ten with RA and ten healthy volunteers) and found one single nucleotide polymorphism (SNP) in the promoter region. We analyzed this SNP (A/G) by restriction fragment length polymorphism method in 155 RA patients and 100 control subjects. While the frequency of A allele in this SNP was similar in RA patients (74.5%) and controls (76.0%), the disease duration in RA patients with genotype GG was shorter than that of patients with genotypes AA/AG and RA patients with genotype GG had a higher probability of being treated with infliximab. We studied the difference in promoter activity between the two alleles by luciferase assay and found that the promoter activity of TTP promoter region with allele A was around two-fold higher than that with allele G. We conclude that this SNP in the promoter region of the TTP gene mildly affects promoter activity, and thus, may influence the disease activity of inflammatory disorders including RA.
Division of Clinical Immunology, Major of Advanced Biomedical Applications, Graduate School of Comprehensive Human Science, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8575, Ibaraki, Japan.
Takeshi
T
Suzuki
Akito
A
Tsutsumi
Hiroyuki
H
Suzuki
Eiji
E
Suzuki
Makoto
M
Sugihara
Yoshifumi
Y
Muraki
Taichi
T
Hayashi
Yusuke
Y
Chino
Daisuke
D
Goto
Isao
I
Matsumoto
Satoshi
S
Ito
Keiji
K
Miyazawa
Takayuki
T
Sumida
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D051816:Tristetraprolin / Q000235:genetics*; D055815:Young Adult
D051816:Tristetraprolin