TNF-alpha promoter polymorphisms, production and susceptibility to multiple sclerosis in different groups of patients.
TNF-alpha production in whole blood cultures upon stimulation with LPS was determined in 179 individuals from 61 families in order to characterise the magnitude of inherited differences in TNF-alpha production. The three families characterised by highest TNF production showed 7.1 +/- 0.3 ng TNF/ml upon culture with 10 ng LPS and 10.2 +/- 0.2 ng TNF/ml upon culture with 1000 ng LPS. in contrast to the three families characterised by the lowest TNF production that showed a production of 1.6 +/- 0.1 ng TNF upon culture with 10 ng and 2.5 +/- 0.2 ng/ml upon culture with 1000 ng LPS/ml. This difference could not be attributed to the promoter polymorphisms -308 G to A. -238 G to A or -376 G to A, although the -238 GA donors produced 2.1 +/- 0.9 ng TNF upon culture with 10 ng endotoxin compared to 3.2 +/- 2.2 ng TNF for the -238 GG donors. In line with these results the frequency of the -238 GG genotype was increased in hospitalized MS patients in a nursing home (100% 238GG, n = 57) compared to MS patients in an outpatient's clinic (94% 238GG, n = 98) or Dutch controls (90% 238GG, n = 180). These results suggest that the -238 GG genotype is differently distributed in hospitalized MS patients in a nursing home.
Huizinga
T W
TW
Department of Rheumatology, Leiden University Hospital, The Netherlands.
Westendorp
R G
RG
Bollen
E L
EL
Keijsers
V
V
Brinkman
B M
BM
Langermans
J A
JA
Breedveld
F C
FC
Verweij
C L
CL
van de Gaer
L
L
Dams
L
L
Crusius
J B
JB
García-Gonzalez
A
A
van Oosten
B W
BW
Polman
C H
CH
Peña
A S
AS
D004198:Disease Susceptibility; D006801:Humans; D009103:Multiple Sclerosis / Q000209:etiology / Q000235:genetics* / Q000276:immunology*; D011110:Polymorphism, Genetic / Q000276:immunology*; D011401:Promoter Regions, Genetic / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha