CLINICAL STUDY No association of two Fas gene polymorphisms with Hashimoto’s thyroiditis and Graves ’ disease

(B J Stuck and M A Pani contributed equally to this work) 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 pro-liferate 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 poly-morphisms in the CTLA-4 gene. Design: We genotyped Caucasian families with at least one offspring affected by Hashimoto’s thyroid-itis (n 95) and Graves ’ disease (n 109) for two Fas gene polymorphisms (g-670 G! A in the pro-moter region, g-154 C! T in exon 7). Methods: Extended transmission disequilibrium and x 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). Conclusion: 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. European Journal of Endocrinology 149 393–39