Tumor necrosis Factor (TNF)-alpha and TNF-beta mediators of inflammatory re
sponses, have been implicated in the pathogenesis of autoimmune diseases. T
he aim of this investigation was to determine whether two promoter region p
olymorphisms of the TNF-alpha gene TNF-alpha(-308) and (TNF-238) and a dete
rminant in the first intron of the TNF-beta gene (TNF-beta(+252)) affect su
sceptibility to systemic sclerosis (scleroderma) (SSc). Fifty patients and
60 healthy blood donors from Japan were genotyped for these markers by poly
merase chain reaction-based methods. Fisher's exact test was used to rest f
or significant associations. Because of very limited variation ac the TNF-a
lpha(-308) and TNF-alpha(-238) loci in the Japanese people, statistical ana
lyses with sufficient power could net be done for these genotypes. However,
the two homozygous genotypes of the TNF-beta(+252) locus were found to be
significantly associated with SSc. Compared to controls, the frequency of t
he TNF-1 genotype was decreased, whereas that of TNF-2 was increased in SSc
patients. The farmer implies an association with resistance, while the lat
ter suggests an association with susceptibility to the disease. These resul
ts show that the TNF-beta(+252) locus plays an important role in the etiopa
thogenesis of SSc. (C) American Society for Histocompatability and Immunoge
netics, 1999. Published by Elsevier Science Inc.