CTLA-4 promoter variants in patients with Graves' disease and Hashimoto's thyroiditis.
Graves' disease (GD) and Hashimoto's thyroiditis (HT) are T-cell mediated organ-specific autoimmune disorders with a genetic predisposition. The cytotoxic T-lymphocyte antigen 4 (CTLA-4) molecule is the predominant receptor for B7 on activated T cells and represents a negative regulator for T-cell function. Since the CTLA-4-guanine at position 49 of exon 1 is associated with susceptibility to GD as well as to HT and IDDM, we investigated a recently detected cytosine/thymine substitution at position -318 within the CTLA-4 promoter region in patients with GD and HT. 125 patients with GD were significantly more often homozygous for cytosine (86% vs. 73% in controls, P=0.006) and less frequently heterozygous for cytosine and thymine (14% vs. 27%, P=0.008). In 64 patients with HT, the distribution was similar but not significant (81% homozygous for cytosine and 16% heterozygous). When correlating the promoter and the exon 1 polymorphism we found the strongest linkage between thymine (promoter) and adenine (exon 1). In conclusion, a promoter variant of the CTLA-4 gene represents an additional risk marker for GD and HT, but their predisposition is linked to the exon 1 alleles.
Braun
J
J
Medical Department I, Center of Internal Medicine, Johann Wolfgang Goethe-University Hospital, Frankfurt/Main, FRG.
Donner
H
H
Siegmund
T
T
Walfish
P G
PG
Usadel
K H
KH
Badenhoop
K
K
D000069594:Abatacept; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D060908:CTLA-4 Antigen; D003596:Cytosine; D014644:Genetic Variation; D006111:Graves Disease / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D018796:Immunoconjugates; D011401:Promoter Regions, Genetic; D013941:Thymine; D013967:Thyroiditis, Autoimmune / Q000235:genetics*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D000069594:Abatacept; D003596:Cytosine; D013941:Thymine