No association of two Fas gene polymorphisms with Hashimoto's thyroiditis and Graves' disease.
BACKGROUND
Apoptosis is a joint pathogenic process underlying autoimmune thyroid disease. Increased programmed cell death in thyrocytes causes hypothyroidism in Hashimoto's thyroiditis, whereas in Graves' disease infiltrating lymphocytes undergo apoptosis while thyrocytes appear to proliferate under protection of anti-apoptotic signals. The Fas/Fas ligand cascade represents a major pathway initiating apoptosis. Its role in autoimmunity is well studied and genetic polymorphisms in gene loci of Fas and its ligand have been shown to be associated with autoimmune diseases.


OBJECTIVE
Due to the functional relevance of the Fas pathway in autoimmune thyroid disease we were interested in the possible contribution of polymorphisms in the Fas gene to the genetic risk of thyroid autoimmunity, which so far is mainly, but incompletely, attributed to the HLA DQ region and polymorphisms in the CTLA-4 gene.


METHODS
We genotyped Caucasian families with at least one offspring affected by Hashimoto's thyroiditis (n=95) and Graves' disease (n=109) for two Fas gene polymorphisms (g-670 G-->A in the promoter region, g-154 C-->T in exon 7).


METHODS
Extended transmission disequilibrium and chi(2) testing were performed.


RESULTS
Neither polymorphism alone (P=0.44 and P=0.70) nor the promoter/exon 7 haplotypes (P=0.86) were associated with Hashimoto's thyroiditis. No association with Graves' disease was observed for the promoter polymorphism (P=0.91) and exon 7 (P=0.65) or the promoter/exon 7 haplotypes (P=0.80).


CONCLUSIONS
In summary, our data do not suggest any significant contribution of common genetic Fas variants to the genetic risk of developing Hashimoto's thyroiditis or Graves' disease.
Department of Internal Medicine I, University Hospital Frankfurt am Main, Theodor-Stern-Kai 7, D-60596 Frankfurt am Main, Germany.
Bettina J
BJ
Stuck
Michael A
MA
Pani
Foued
F
Besrour
Maria
M
Segni
Maren
M
Krause
Klaus-H
KH
Usadel
Klaus
K
Badenhoop
D005192:Family Health; D005260:Female; D006111:Graves Disease / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D013967:Thyroiditis, Autoimmune / Q000235:genetics*; D019014:fas Receptor / Q000235:genetics*
D019014:fas Receptor