Polymorphism of the 5'-flanking region of the human tumor necrosis factor (TNF)-alpha gene in Japanese.
Polymorphism of the 5'-flanking promoter/enhancer region of the TNF-alpha gene in Japanese is not well understood. To better understand it, we have determined the 1,358 base pair sequence of the 5'-flanking region of the TNF-alpha gene in nine Japanese, and identified three new polymorphisms at positions 1,031 (T to C change, termed as -1,031C), -863 (C to A, -863A), and -857 (C to T, -857T), with the former two in one allele. The level of TNF-alpha production by concanavalin A (Con A)-activated peripheral blood mononuclear cells from the five donors possessing at least one new allele was 1.8-fold higher than that from the remaining four donors with the dominant allele. The transcriptional promoter activity of the 1,031C/-863A or -857T allele in response to Con A stimulation was 2.0 or 1.7-fold higher than that of the dominant allele, respectively. The allele frequencies of -1,031C, -863A, -857T, -308A (G to A), and -238A (G to A) (the latter two were previously reported) in 575 healthy Japanese were 16.0, 14.0, 17.7, 1.7 and 2.0%, respectively. The -1,031C/-863A or -857T allele was in significant linkage disequilibrium with HLA-B61, -B39 and -DRB1*0901, or with HLA-B54, -B35, -B59, and -DRB1*0405, respectively. The newly identified alleles observed in a relatively large proportion of Japanese may be related to differences in levels of TNF-alpha production in immune responses to various stimuli among individuals.
Department of Immunology, Kurume University School of Medicine, Japan.
T
T
Higuchi
N
N
Seki
S
S
Kamizono
A
A
Yamada
A
A
Kimura
H
H
Kato
K
K
Itoh
D000483:Alleles; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D005787:Gene Frequency; D006801:Humans; D007564:Japan; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008934:Mitogens / Q000494:pharmacology; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics*
D008934:Mitogens; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A