Tumour necrosis factor-beta gene RFLP alleles in Finnish IDDM haplotypes. The Childhood Diabetes in Finland (DiMe) Study Group.
The genes located between class II and class I HLA genes including polymorphic tumour necrosis factor (TNF) genes may contribute to the disease susceptibility in IDDM. Restriction fragment polymorphisms of the TNF-beta gene have been found to be fixed in the major IDDM susceptibility haplotypes, the B62,DR4 haplotype being associated with the 10.5-kb fragment and the B8,DR3 haplotype with a 5.5-kb fragment. We studied this TNF polymorphism in a sample of diabetic families. In all IDDM-associated haplotypes (n = 129) the 5.5-kb allele was more frequent than in haplotypes found only in healthy family members (n = 112) (58.1% versus 40.2%, P < 0.01). Among IDDM haplotypes the B62,DR4 haplotype was characterized by the 10.5-kb TNF fragment, whereas two other common Finnish IDDM-associated DR4 haplotypes--A24,B39,DR4 and A2,B56,DR4--had the 5.5-kb TNF fragment. Both IDDM-associated and non-associated DR3 positive haplotypes were linked to the 5.5-kb fragment. The distribution of various combinations of TNF alleles in IDDM probands (n = 63) did not differ from that expected according to the Hardy-Weinberg distribution. Our results indicate that the 10.5-kb allele of TNF-beta gene as such is not a risk factor contributing to DR4/DQ8-associated susceptibility. Alternatively, there may be heterogeneity in pathogenetic effector mechanisms.
Ilonen
J
J
Department of Virology, University of Turku, Finland.
Merivuori
H
H
Reijonen
H
H
Knip
M
M
Akerblom
H K
HK
Pociot
F
F
Nerup
J
J
D000483:Alleles; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005387:Finland; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006684:HLA-DR Antigens / Q000032:analysis; D006239:Haplotypes; D006801:Humans; D016130:Immunophenotyping; D008233:Lymphotoxin-alpha / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length
D006684:HLA-DR Antigens; D008233:Lymphotoxin-alpha