Bettinotti, M. P.; Hartung, K.; Deicher, H.; Messer, Gerald; Keller, E.; Weiss, Elisabeth H.; Albert, E. D.
Polymorphism of the tumor necrosis factor beta gene in systemic lupus erythematosus. TNFB-MHC haplotypes.
In: Immunogenetics, Vol. 37: pp. 449-454
We investigated the Nco I restriction fragment
length polymorphism (RFLP) of the tumor necrosis
factor beta (TNFB) gene in 173 patients with systemic
lupus erythematosus (SLE), 192 unrelated
healthy controls, and eleven panel families, all of German
origin. The phenotype frequency of the TNFB*I
allele was significantly increased in patients compared
to controls (63.6% vs 47.1%, RR = 1.96, p <0.002).
The results of a two-point haplotype statistical analysis
between TNFB and HLA alleles show that there is linkage
disequilibrium between TNFB*I and HLA-A1,
Cw7, B8, DR3, DQ2, and C4A DE. The frequency of
TNFB*I was compared in SLE patients and controls in
the presence or absence of each of these alleles.
TNFB*I is increased in patients over controls only in
the presence of the mentioned alleles. Therefore, the
whole haplotypeA1, Cw7, B8, TNFB* I, C4A DE, DR3,
DQ2 is increased in patients and it cannot be determined
which of the genes carried by this haplotype is
responsible for the susceptibility to SLE. In addition,
two-locus associations were analyzed in 192 unrelated
healthy controls for TNFB and class I alleles typed by
serology, and for TNFB and class II alleles typed by
polymerase chain reaction/oligonucleotide probes. We
found positive linkage disequilibrium between
TNFB*I and the following alleles: HLA-A24, HLA-B8,
DRBI*0301, DRBI*ll04, DRBI*1302, DQAI*0501, DQBI*0201, DQBI*0604, and DPBI*OIO1. TNFB*2
is associated with HLA-B7, DRBI*1501, and
DQB I *0602.